. _:b213193867 . . _:b213193568 . _:b213193866 . . _:b213193877 . _:b213194336 . _:b213193876 . . . _:b213193566 . _:b213193879 . _:b213193878 . . . _:b213193873 . . _:b213193872 . _:b213193875 . . _:b213193874 . . . . _:b213193885 . _:b213193679 . _:b213193437 . . _:b213193884 . _:b213193887 . _:b213194136 . _:b213193886 . _:b213193641 . _:b95141 "Note that whereas all replicons associate with the nuclear matrix as replication occurs (data not shown; Pardoll et al., >>1980<<), this analysis is performed on unsynchronized cells, so that only a small fraction will have previously labeled foci that are undergoing replication at the time of extraction." . _:b213193881 . _:b213193413 . _:b95161 "4) and that aberrant initiation events arise rarely (Jackson, 1995a )." . _:b213194012 . _:b213193880 . _:b213194109 . _:b213193618 . _:b213193883 . _:b95159 . _:b213194105 . . _:b213193882 . _:b213193893 . _:b213194578 . . _:b213193892 . _:b213193411 . _:b213193895 . . _:b213193673 . _:b213194475 . _:b213193894 . _:b213194496 . . _:b213193889 . _:b213193888 . _:b213193891 . _:b213193345 . . _:b213193890 . . _:b213194153 . _:b213193901 . _:b213193900 . _:b213193903 . _:b213193902 . _:b213194204 . _:b213193897 . _:b213193896 . . _:b213193899 . _:b213193514 . . _:b213193898 . . _:b213193909 . _:b213193908 . _:b213194233 . _:b213193911 . _:b213193910 . _:b213193581 . _:b213193905 . . _:b213193904 . . _:b213193328 . _:b213193529 . . _:b213193907 . . . _:b213193906 . _:b213193917 . . . _:b213193916 . . _:b213193919 . _:b213193750 . _:b213193918 . . _:b213193913 . _:b213193912 . _:b213193915 . . _:b213193500 . . _:b213193561 . . _:b213193914 . _:b213193925 . _:b213193924 . _:b213193927 . . . _:b213193926 . _:b213194394 . . _:b213193921 . . _:b213193920 . . _:b213193923 . _:b213193922 . _:b213193933 . . _:b213194364 . _:b213194219 . . _:b213193932 . . _:b213193935 . _:b213193851 . _:b213193934 . _:b213193929 . _:b213193928 . _:b95170 "(Nakamura et al., 1986; Humbert and Usson, 1992; Tomilin et al., 1995), and is known to reflect the natural distribution of replication proteins (Kill et al., 1991; Krude, 1995), ancillary proteins (Leonhardt et al., 1992; Krude, >>1995<<), and particular DNA sequences that replicate at known times of S phase (O'Keefe et al., 1992)." . _:b213193931 . _:b213193617 . _:b213193930 . . . _:b213193941 . _:b95193 . . _:b213193940 . _:b213194513 . _:b95169 . _:b213193943 . _:b213193942 . _:b213193937 . _:b213193936 . _:b213193939 . _:b213194172 . . _:b213193938 . _:b213193950 . _:b213193478 . _:b213193949 . _:b213194253 . . _:b213193502 . _:b213193948 . _:b213193923 . . _:b213193951 . . _:b213194571 . . . . . _:b213193950 . . _:b213193945 . _:b213194363 . _:b213193944 . . _:b213193765 . _:b213193947 . . _:b213193946 . . _:b213193957 . _:b213193956 . _:b213194086 . _:b95177 "This is many more than the \u223C126 sites identified in rat fibroblasts, using indirect immunofluorescence of early\u2013S phase cells labeled with BrdU (Nakamura et al., >>1986<<). However, in later studies, technical improvements increased the number of sites in mouse 3T3 cells to \u223C250 (Fox et al., 1991), and then \u223C600 (Berezney et al., 1995b ), in line with the number seen here." . _:b213194566 . _:b213193959 . . _:b213193958 . _:b213194037 . _:b213193953 . _:b213193952 . . . _:b213193955 . _:b213193954 . _:b213193965 . _:b213193964 . . _:b213193967 . _:b213193966 . _:b213193961 . _:b213193535 . _:b213193686 . _:b213193960 . . _:b213193963 . . _:b95171 "the natural distribution of replication proteins (Kill et al., 1991; Krude, 1995), ancillary proteins (Leonhardt et al., 1992; Krude, 1995), and particular DNA sequences that replicate at known times of S phase (O'Keefe et al., >>1992<<). Once labeled, replication foci also present a useful tool for the analysis of genome organization (for review see Drouin et al., 1994; Dolbeare, 1996)." . _:b213193962 . _:b213194597 . . _:b213193973 . _:b213193972 . . _:b213193975 . . _:b213194399 . _:b213193974 . . _:b213193969 . _:b213193968 . _:b213193781 . _:b213193971 . _:b213193946 . _:b213193970 . _:b213193981 . _:b213193980 . _:b213193983 . . _:b213193556 . _:b213193982 . _:b213193977 . . . _:b213193976 . _:b213193806 . _:b213193341 . . _:b213194067 . _:b213193979 . . . _:b213193978 . _:b213193371 . . _:b213193477 . _:b213193476 . . _:b213193479 . _:b213193478 . . _:b213193473 . _:b213193472 . . _:b213193475 . _:b213193474 . . . _:b213193485 . . _:b213193484 . _:b213193487 . _:b213193486 . . _:b213193481 . _:b213194048 . _:b95166 . _:b213193480 . _:b213193483 . _:b213193662 . . _:b213193482 . _:b213193877 . . _:b213193493 . . . . _:b213193492 . _:b213193495 . _:b213194180 . _:b213193494 . _:b213194418 . _:b213193489 . _:b213194333 . _:b213193488 . _:b213194289 . _:b213194000 . _:b213193491 . _:b213193490 . _:b213193501 . _:b213193500 . . _:b213193503 . _:b213193730 . _:b213193502 . . . _:b213193497 . _:b213193496 . _:b213193499 . . . _:b213193397 . _:b213193498 . . _:b95158 "Indeed, whereas DNA fibers spread as described here can stretch to as much as twice their expected length (Parra and Windle, >>1993<<) the average values for different sequences visualized by fluorescence in situ hybridization (FISH) are usually within 10% of that expected for DNA in solution." . _:b213193509 . _:b213193508 . _:b213194108 . _:b213193511 . _:b213193510 . . _:b213193505 . _:b213193365 . _:b213193504 . _:b213193507 . . _:b213193506 . . _:b213193517 . . _:b213193516 . _:b213193846 . _:b213193519 . _:b213194281 . _:b213193518 . _:b213193513 . _:b213193512 . _:b213193515 . _:b213194564 . _:b213193514 . _:b213193525 . _:b213193524 . _:b213194520 . . . _:b213193527 . . _:b213193526 . . _:b213193521 . . . _:b213193520 . _:b213194061 . _:b213193523 . _:b213193522 . _:b213193533 . _:b213193532 . _:b213193535 . _:b213194544 . _:b213193534 . . _:b213193529 . _:b95191 "elements on extrachromosomal episomes, and the apparent promiscuity of DNA fragments that are >20 kbp, imply that simple sequence elements are not sufficient to drive S phase in mammalian cells (for review see Coverley and Laskey, >>1994<<). As a result, it has been argued that chromosome structure and/or nuclear organization might play important roles during the S phase of higher eukaryotic cells (Coverley and Laskey, 1994; DePamphilis, 1996)." . . _:b95183 . _:b213193528 . _:b213193531 . . _:b213193530 . _:b213193541 . _:b213194404 . _:b213193540 . _:b95196 "As synthesis progresses, secondary sites are activated adjacent to the primary ones (Manders et al., 1992, >>1996<<; Berezney et al., 1995b ), and in clusters that are activated at different times, but that contain replicons activated together (Fig." . _:b213193543 . _:b213193861 . . _:b213193542 . _:b213193537 . . _:b213193536 . _:b213193539 . _:b213194309 . . _:b213193538 . . _:b213193761 . . _:b213193388 . . _:b213193549 . . _:b213193548 . . _:b213194160 . _:b213193440 . _:b213193551 . _:b213193550 . . _:b213193545 . . . _:b213194385 . _:b213193544 . . _:b213193547 . _:b213193546 . . _:b213193557 . _:b213193556 . _:b213193559 . _:b213193715 . _:b95122 "To prepare extended DNA fibers (Parra and Windle, >>1993<<), 2 \u03BCl cells resuspended in PBS (106 cells/ml) were spotted onto cleaned glass slides and lysed with 5 \u03BCl of 0.5% SDS in 200 mM Tris-HCl, pH 7.4, 50 mM EDTA (10 min, 20\u00B0C)." . _:b213194290 . _:b213193558 . _:b213193553 . _:b213193552 . . _:b213193555 . _:b213193554 . . _:b213193565 . _:b213193564 . _:b213193567 . _:b213193634 . _:b213193566 . . . _:b213193561 . . _:b213193754 . _:b213193560 . . _:b213193563 . _:b213193729 . . _:b213193562 . _:b213193573 . _:b213194473 . _:b213193572 . _:b213194267 . _:b213193391 . _:b213193575 . . . _:b95121 . _:b213193574 . . _:b213193569 . _:b213193548 . . . _:b213193568 . _:b213193571 . . _:b213193570 . _:b213194325 . . _:b213193581 . _:b213194457 . _:b213193580 . _:b213193800 . _:b213193583 . _:b213193582 . . _:b213194374 . _:b213193577 . . _:b213193376 . _:b213193576 . _:b213194360 . _:b213193579 . _:b213194501 . . _:b213193578 . . _:b213193589 . _:b213193588 . _:b213193591 . _:b213193590 . _:b213193585 . _:b213193382 . _:b213193584 . _:b213193587 . . _:b213193586 . _:b213193469 . _:b213193597 . _:b213193596 . _:b213193599 . _:b213193598 . . . _:b213193593 . _:b213194570 . _:b213193592 . _:b213193595 . . _:b213193594 . . _:b213193605 . _:b213193771 . _:b213194410 . _:b213193604 . _:b213193607 . _:b213194055 . _:b213193606 . _:b213193479 . _:b213193601 . . _:b213193600 . _:b213193603 . _:b213193602 . _:b213193613 . _:b213193612 . . _:b213193615 . . _:b213193614 . _:b213193609 . _:b213194039 . _:b213193971 . _:b213193486 . _:b213193569 . _:b213193608 . . _:b213193611 . . _:b95147 . _:b213193610 . . _:b213193621 . . _:b213193620 . _:b213194398 . . _:b213193623 . _:b95142 "discussion" . . _:b213193622 . . _:b213193617 . _:b213193356 . . _:b213193616 . _:b213193619 . _:b213193618 . _:b213193629 . _:b213194138 . _:b95121 "To label sites of transcription, G1 phase HeLa cells (4 h after removing nocodazole) encapsulated in agarose microbeads (2.5 \u00D7 106/ml; Jackson and Cook, >>1985<<) were incubated for 5 min in medium supplemented with 2.5 mM bromouridine." . _:b213193628 . . _:b213193631 . _:b213193630 . _:b213193796 . . . _:b213193625 . . . . _:b213193624 . _:b213193448 . _:b213194085 . _:b213193627 . _:b213193626 . _:b213193637 . . _:b95151 "appearance of mitotic chromosomes confirms that they are highly organized (Holmquist, 1992), the molecular features responsible remain ill-defined (Earnshaw, 1988; Manuelidis and Chen, 1990; Saitoh and Laemmli, 1994; Cook, >>1995<<). However, different aspects of chromosome structure are known to correlate with nuclear function." . _:b213193636 . _:b213194536 . _:b213193639 . . _:b213193638 . _:b213193855 . . _:b213193409 . _:b213193633 . . _:b213193532 . . . . _:b213193632 . _:b213193635 . _:b213194207 . . _:b213193634 . _:b213193645 . _:b213193644 . . _:b213193416 . _:b213193647 . . _:b213193646 . _:b213193641 . _:b213193640 . . _:b213193643 . _:b213194041 . _:b213193642 . _:b213193653 . . _:b213194165 . _:b213193652 . . _:b213193655 . _:b213193654 . . _:b213193649 . _:b213194069 . _:b213193648 . _:b213193605 . _:b213193651 . _:b213193917 . . . _:b213193650 . _:b213193661 . . _:b213193660 . _:b213193598 . _:b213194114 . _:b213193663 . . . _:b213193662 . _:b95153 . _:b213193657 . . _:b213193656 . _:b95129 "The DNA precursor analogue BrdU provides a facile means of labeling DNA in eukaryotic cells (Dolbeare, 1995, >>1996<<). S phase cells grown for 20 min in medium supplemented with BrdU incorporate the analogue into active sites of DNA synthesis (Nakamura et al., 1986)." . _:b213193463 . _:b213193659 . _:b213194071 . _:b213193658 . _:b213193669 . _:b213193668 . _:b95144 . _:b213193671 . . _:b213193670 . . _:b213193665 . _:b213193664 . _:b213194305 . _:b213193667 . . _:b213193666 . _:b213193677 . _:b213194381 . _:b213193676 . . . . _:b213193679 . _:b213193462 . _:b213193678 . _:b213193673 . _:b213193983 . _:b213193672 . . _:b213193675 . _:b213193674 . _:b213194482 . _:b213193685 . _:b213194526 . _:b213193684 . _:b213193687 . _:b213193686 . . _:b213193681 . . _:b213193680 . _:b213194201 . _:b213193690 . _:b213193683 . _:b213194001 . _:b213194075 . _:b213193560 . _:b213193682 . _:b213193454 . _:b213193693 . _:b213193692 . _:b213193732 . _:b213193695 . . _:b213193965 . _:b213193694 . _:b213194157 . . . _:b213193689 . _:b213193688 . _:b213193691 . _:b213193690 . _:b213194068 . _:b213193701 . . _:b213194117 . _:b213193700 . . _:b213194452 . _:b213193703 . . _:b213193702 . . _:b213193697 . . _:b213193696 . . _:b213193699 . . . _:b213193698 . . _:b213193709 . . _:b213193708 . _:b213193763 . _:b213193711 . . _:b213193710 . . _:b213193705 . . _:b213193704 . . _:b213194415 . _:b213193707 . _:b213193706 . . _:b213193717 . . _:b213193511 . _:b213194159 . _:b213193716 . _:b213193719 . _:b213194575 . _:b213193718 . _:b213194414 . _:b213193713 . . _:b213193712 . . _:b213193715 . . _:b213193714 . . _:b213193725 . . . . _:b213193724 . _:b213193655 . . _:b213193727 . _:b213194043 . _:b213193726 . _:b213193721 . _:b95146 "In higher eukaryotes, with much more complex genomes, the elusive nature of replication origins (Coverley and Laskey, >>1994<<) has prompted the suggestion that an efficient S phase will rely on \u201Cthe interplay between specific DNA sequences, chromosome structure and nuclear organization\u201D (DePamphilis, 1996)." . _:b213193653 . _:b213193720 . _:b95157 . _:b213193723 . . _:b213193585 . _:b213194245 . _:b213193722 . _:b213193640 . . _:b213193856 . _:b213194516 . _:b213194052 . . . _:b95168 . _:b213194307 . _:b213194523 . _:b95187 "This approach allows interphase chromosome domains to be seen using conditions that are much less destructive than those used to visualize chromosome territories by FISH (Schardin et al., >>1985<<; Manuelidis, 1985)." . _:b95170 . _:b213194300 . . _:b213193668 . _:b213194492 . _:b213194226 . _:b213193360 . . _:b213194350 . _:b213193325 . _:b213193910 . . . _:b213193430 . . . _:b213194458 . . . _:b95198 . . _:b213193764 . _:b213193613 . . _:b213194294 . _:b95139 "Cells synchronized so that >90% are in S phase are known to develop a variety of replication defects (Jackson 1995a ); hence, it is not possible to label authentic sites of initiation in two consecutive cell cycles with high efficiency." . _:b213193606 . _:b213194497 . _:b213193666 . _:b213193960 . . . . . . _:b213194326 . . . _:b213194577 . _:b213193580 . _:b213194409 . _:b213194434 . . _:b213194004 . . _:b213193770 . . . _:b213193402 . _:b95162 . . _:b213194329 . _:b213193782 . . . _:b213193694 . . _:b213194009 . _:b213194155 . . _:b213194576 . . _:b213194258 . _:b213193464 . _:b213193691 . . _:b213193860 . . . _:b213193688 . . . . . _:b213194107 . _:b213194358 . _:b213193658 . _:b213194205 . . _:b213193361 . _:b213194168 . _:b213194557 . _:b213194572 . _:b213194278 . . _:b95128 . . . . _:b213194528 . _:b213193480 . . _:b213193563 . _:b213194436 . . . _:b213194074 . . . . _:b213194518 . _:b213194245 "2"^^ . _:b213193528 . _:b213194332 . _:b213194244 "2"^^ . _:b213193554 . _:b213193867 . _:b213193537 . _:b213193894 . . _:b213194247 "2"^^ . _:b213193508 . _:b213194246 "2"^^ . _:b213193325 . _:b213194241 "2"^^ . _:b95178 "However, in later studies, technical improvements increased the number of sites in mouse 3T3 cells to \u223C250 (Fox et al., >>1991<<), and then \u223C600 (Berezney et al., 1995b ), in line with the number seen here." . _:b213193324 . _:b213194240 "2"^^ . . _:b213193327 . _:b213194243 "2"^^ . . _:b213193326 . _:b213194242 "2"^^ . _:b213194253 "2"^^ . _:b213193327 . _:b213194252 "2"^^ . _:b95149 "Whereas the characteristic appearance of mitotic chromosomes confirms that they are highly organized (Holmquist, 1992), the molecular features responsible remain ill-defined (Earnshaw, 1988; Manuelidis and Chen, >>1990<<; Saitoh and Laemmli, 1994; Cook, 1995). However, different aspects of chromosome structure are known to correlate with nuclear function." . _:b213193323 . _:b213194255 "2"^^ . _:b213193865 . _:b213194254 "2"^^ . _:b213193333 . _:b213194249 "2"^^ . _:b213193869 . _:b213194301 . _:b213193332 . _:b213194248 "2"^^ . _:b213193517 . . _:b213193335 . _:b213194251 "2"^^ . _:b213193334 . _:b213194250 "2"^^ . _:b213193329 . _:b213194261 "2"^^ . _:b213193328 . _:b213194260 "2"^^ . _:b213193331 . _:b213194263 "2"^^ . _:b213193330 . _:b213194262 "2"^^ . . _:b213193341 . _:b213194257 "2"^^ . _:b213193809 . _:b213193340 . _:b213194256 "2"^^ . _:b213193343 . _:b213194259 "2"^^ . _:b213193929 . _:b213193874 . _:b213193342 . _:b213194258 "2"^^ . _:b213193343 . _:b213193337 . _:b213194269 "2"^^ . _:b213193429 . _:b213193336 . _:b213194268 "2"^^ . . _:b213194191 . _:b213194271 "2"^^ . _:b213193339 . _:b213193338 . _:b213194270 "2"^^ . . _:b213193349 . _:b213194573 . _:b213194265 "2"^^ . _:b213193348 . _:b213194264 "2"^^ . _:b213193351 . _:b213194267 "2"^^ . _:b213193439 . . _:b213194149 . _:b213193350 . _:b213194266 "2"^^ . _:b213193345 . _:b213194277 "2"^^ . _:b213193935 . . _:b213193344 . _:b213194276 "2"^^ . _:b213193347 . _:b213194279 "2"^^ . . . _:b213193346 . _:b213194278 "2"^^ . . _:b213193357 . _:b213194273 "2"^^ . _:b213193356 . _:b213194272 "2"^^ . _:b213194197 . _:b213193359 . _:b213194275 "2"^^ . . _:b213193358 . _:b213194274 "2"^^ . _:b213193353 . _:b213194285 "2"^^ . _:b213193352 . _:b213194284 "2"^^ . _:b213193355 . _:b213194287 "2"^^ . . . _:b213193354 . _:b213194286 "2"^^ . _:b213194530 . . _:b213194281 "2"^^ . _:b213193365 . . _:b213193364 . _:b213194280 "2"^^ . . . _:b213193367 . _:b213194283 "2"^^ . _:b213193366 . _:b213194282 "2"^^ . _:b213193833 . _:b213193361 . _:b213194293 "2"^^ . _:b213193360 . _:b213194292 "2"^^ . _:b213193363 . _:b213194295 "2"^^ . _:b213193362 . _:b213194294 "2"^^ . _:b95196 . _:b213194011 . _:b213194289 "2"^^ . _:b213193373 . . _:b213193372 . _:b213194288 "2"^^ . _:b213193375 . _:b213194291 "2"^^ . _:b213193374 . _:b213194290 "2"^^ . . _:b213193369 . _:b213194301 "2"^^ . _:b213194072 . _:b213193368 . _:b213194300 "2"^^ . _:b213194474 . _:b213193371 . _:b213194303 "2"^^ . _:b213193819 . _:b213193370 . _:b213194302 "2"^^ . . . . . . _:b213194297 "2"^^ . _:b213193381 . _:b213193497 . _:b213193380 . _:b95122 . _:b213194296 "2"^^ . _:b213194556 . _:b213193383 . _:b213194299 "2"^^ . _:b213193382 . _:b213194298 "2"^^ . . _:b213193377 . _:b213194551 . _:b213194309 "2"^^ . _:b213193376 . _:b213194308 "2"^^ . _:b213193379 . _:b213194311 "2"^^ . _:b213193378 . _:b213194310 "2"^^ . _:b213193389 . _:b213194305 "2"^^ . _:b213194591 . . _:b213194304 "2"^^ . _:b213193388 . _:b213193391 . _:b213194307 "2"^^ . _:b213193390 . _:b213194306 "2"^^ . _:b213194598 . _:b213193385 . _:b213194317 "2"^^ . _:b213194269 . _:b213193384 . _:b213194316 "2"^^ . _:b213193387 . _:b213194319 "2"^^ . _:b213193386 . _:b213194318 "2"^^ . _:b213193397 . _:b213194313 "2"^^ . . _:b213194312 "2"^^ . _:b213193396 . . _:b213194315 "2"^^ . _:b213193399 . . . _:b213194277 . _:b213194314 "2"^^ . _:b213193398 . _:b213193393 . _:b213194325 "2"^^ . . _:b213194324 "2"^^ . _:b213193392 . _:b213193395 . _:b213194327 "2"^^ . . _:b213193460 . _:b213193394 . _:b213194326 "2"^^ . _:b213193405 . _:b213194321 "2"^^ . _:b213193404 . _:b213194320 "2"^^ . _:b213193924 . . _:b213193407 . _:b213194323 "2"^^ . . _:b213194273 . . _:b213194322 "2"^^ . _:b213193406 . _:b213193401 . _:b213194333 "2"^^ . . _:b213194443 . . _:b213194332 "2"^^ . _:b213193400 . . _:b213193403 . _:b213194335 "2"^^ . _:b213193402 . _:b213194334 "2"^^ . _:b213193413 . _:b213194329 "2"^^ . _:b213193696 . _:b213193948 . . _:b213193412 . _:b213194328 "2"^^ . _:b213193415 . _:b213194331 "2"^^ . _:b213193414 . _:b213194330 "2"^^ . . _:b213193409 . _:b213194341 "2"^^ . _:b213193408 . _:b95158 . _:b213194340 "2"^^ . _:b213193411 . _:b213194343 "2"^^ . _:b213193410 . _:b213194342 "2"^^ . _:b213193421 . _:b213194337 "2"^^ . _:b213193420 . _:b213194336 "2"^^ . _:b213193423 . _:b213194339 "2"^^ . . _:b213193422 . _:b213194338 "2"^^ . _:b213193417 . _:b213194349 "2"^^ . . _:b213193416 . _:b213194348 "2"^^ . . . _:b213193700 . . _:b213194351 "2"^^ . _:b213193419 . . _:b213193418 . _:b213194350 "2"^^ . _:b213194365 . _:b213193429 . _:b213194345 "2"^^ . _:b213193407 . _:b213194014 . _:b213193428 . _:b213194344 "2"^^ . _:b213193431 . _:b213194347 "2"^^ . _:b95142 . _:b213193780 . _:b213193430 . _:b213194346 "2"^^ . _:b213193425 . _:b213194357 "2"^^ . _:b213193821 . _:b213193933 . _:b213193424 . _:b213194356 "2"^^ . _:b213193427 . _:b213194359 "2"^^ . _:b95127 . _:b213194358 "2"^^ . _:b213193426 . _:b213193916 . _:b213194353 "2"^^ . _:b213193437 . _:b213193943 . _:b213193436 . _:b213194352 "2"^^ . _:b95119 . _:b213193551 . . _:b213194355 "2"^^ . _:b213193439 . _:b213193804 . _:b213193438 . _:b213194354 "2"^^ . _:b213194194 . _:b213193457 . _:b213194594 . _:b213193433 . _:b213194365 "2"^^ . . . _:b213193432 . _:b213194364 "2"^^ . _:b213193543 . _:b213193435 . _:b213194367 "2"^^ . . _:b213193434 . _:b95137 . _:b213194366 "2"^^ . _:b213193445 . _:b213194361 "2"^^ . _:b213193444 . _:b213194360 "2"^^ . _:b213194314 . . _:b213193447 . _:b213194363 "2"^^ . _:b213194162 . _:b213193446 . _:b213194362 "2"^^ . _:b213194171 . _:b213193441 . _:b213194373 "2"^^ . . _:b213193928 . _:b213194433 . . _:b213193440 . _:b213194372 "2"^^ . . _:b213194447 . . . _:b213194375 "2"^^ . _:b213193443 . _:b213193442 . _:b213194374 "2"^^ . . . _:b213193453 . _:b213194369 "2"^^ . . _:b213193452 . _:b213194368 "2"^^ . . . _:b213193455 . _:b213194371 "2"^^ . _:b213194413 . . . _:b213193454 . _:b213194370 "2"^^ . . _:b213193449 . _:b213194381 "2"^^ . . _:b213193524 . _:b213193448 . _:b213194380 "2"^^ . _:b213193451 . _:b213194383 "2"^^ . _:b213194382 "2"^^ . _:b213193450 . _:b213194176 . . _:b213194377 "2"^^ . _:b95197 . _:b213193461 . . . _:b213194376 "2"^^ . _:b95194 . _:b213193460 . _:b213194379 "2"^^ . . _:b213193463 . _:b213193967 . _:b213193632 . . _:b213194378 "2"^^ . _:b213193462 . _:b95163 "It is a routine matter to label sites of replication using BrdU, a DNA precursor analogue that can be detected after incorporation into nascent DNA (for review see Dolbeare, 1995, >>1996<<). The appearance of the labeled replication sites has been described in detail (Nakamura et al., 1986; Humbert and Usson, 1992; Tomilin et al., 1995), and is known to reflect the natural distribution of replication proteins (Kill et al.," . _:b213194389 "2"^^ . _:b213193457 . _:b213193756 . _:b213194388 "2"^^ . _:b213193456 . . . _:b213194390 . _:b213194391 "2"^^ . _:b213193459 . _:b213193981 . _:b213194390 "2"^^ . _:b213193458 . . _:b213194385 "2"^^ . _:b213193469 . _:b213194384 "2"^^ . _:b213193468 . . _:b213194387 "2"^^ . _:b213193471 . _:b213194386 "2"^^ . _:b213193470 . _:b213194397 "2"^^ . _:b213193465 . . _:b213193783 . _:b213194396 "2"^^ . _:b213194466 . _:b213193464 . . _:b213193918 . . . . . _:b213194399 "2"^^ . _:b213193467 . _:b213193441 . _:b213194398 "2"^^ . _:b213193466 . _:b213193969 . _:b213194393 "2"^^ . _:b213194585 . . _:b213194392 "2"^^ . _:b213194395 "2"^^ . _:b213193739 . _:b213194394 "2"^^ . _:b95164 . . _:b213194405 "2"^^ . . _:b213194404 "2"^^ . _:b213194407 "2"^^ . . _:b213194406 "2"^^ . _:b213194401 "2"^^ . _:b213194143 . _:b213194400 "2"^^ . _:b213194403 "2"^^ . _:b213194542 . _:b213194461 . . _:b213194402 "2"^^ . . _:b213194413 "2"^^ . . _:b213194412 "2"^^ . . _:b213193593 . _:b213194040 . _:b213194415 "2"^^ . . _:b213194414 "2"^^ . _:b213194057 . . . _:b213194409 "2"^^ . . _:b213194408 "2"^^ . _:b213193748 . _:b213194411 "2"^^ . . . . _:b213194410 "2"^^ . . _:b213194421 "2"^^ . . _:b213194420 "2"^^ . _:b213194442 . _:b213194423 "2"^^ . . _:b213194422 "2"^^ . _:b213194417 "2"^^ . _:b213194416 "2"^^ . _:b213194419 "2"^^ . . _:b213194418 "2"^^ . _:b213193607 . _:b213194429 "2"^^ . _:b95183 "Foci clearly persist into mitosis (Sparvoli et al., 1994), where the expected daughter foci (Baumgartner et al., >>1991<<) can be seen on adjacent chromatid arms (Fig." . . _:b213194428 "2"^^ . _:b95130 . _:b213194431 "2"^^ . _:b213194195 . _:b213194430 "2"^^ . _:b213194425 "2"^^ . _:b213194424 "2"^^ . _:b213193530 . _:b213194493 . _:b213194427 "2"^^ . . _:b213194426 "2"^^ . _:b213193675 . _:b95132 . _:b213194437 "2"^^ . _:b213193424 . _:b213194436 "2"^^ . . _:b213194439 "2"^^ . _:b213194438 "2"^^ . _:b213193512 . _:b213194433 "2"^^ . _:b213194432 "2"^^ . . _:b213194435 "2"^^ . _:b213194434 "2"^^ . _:b213194445 "2"^^ . _:b213193639 . _:b213194444 "2"^^ . _:b213193406 . _:b213194447 "2"^^ . _:b213194446 "2"^^ . _:b213194441 "2"^^ . _:b213194469 . _:b213193425 . . _:b213194440 "2"^^ . . _:b213194443 "2"^^ . _:b95131 . _:b213194442 "2"^^ . _:b213194134 . . _:b213193760 . _:b213194453 "2"^^ . _:b213194452 "2"^^ . _:b213193648 . _:b213194455 "2"^^ . _:b213193900 . _:b213194454 "2"^^ . _:b95124 . _:b213193886 . _:b213194449 "2"^^ . . _:b213194448 "2"^^ . _:b213194451 "2"^^ . _:b95197 "As the activation of origins that fire within S phase is dependent on the completion of replicons activated earlier (Jackson, 1995a ; Fig. 4), it follows that events occurring during any one phase of synthesis are coupled to the activation of the next phase. As very similar numbers of synthetic sites are active at any time during the first 3 h of S phase, it is" . . _:b213194607 . _:b213193982 . _:b95120 . _:b213194450 "2"^^ . _:b213194246 . _:b213193403 . _:b213194461 "2"^^ . _:b213193505 . _:b213194460 "2"^^ . _:b213193909 . _:b213193968 . _:b213193712 . _:b213194463 "2"^^ . _:b213193384 . _:b95192 "As a result, it has been argued that chromosome structure and/or nuclear organization might play important roles during the S phase of higher eukaryotic cells (Coverley and Laskey, >>1994<<; DePamphilis, 1996)." . _:b95184 "When nuclei reform after mitosis, the daughter cells contain foci similar in appearance to those seen in the previous S phase (Fig. 1; Sparvoli et al., >>1994<<)." . _:b213193385 . _:b213193386 . _:b213193387 . _:b213194462 "2"^^ . _:b213193388 . . _:b213193389 . _:b213193390 . _:b213193391 . _:b213194559 . _:b213194457 "2"^^ . _:b213193376 . _:b213193377 . _:b213193378 . _:b213193379 . _:b213194599 . _:b213194456 "2"^^ . _:b213194161 . _:b213193380 . _:b213193574 . _:b213193381 . _:b213193844 . _:b213193382 . _:b213193932 . _:b213193383 . _:b213194459 "2"^^ . _:b213193400 . _:b213193401 . _:b213193402 . _:b213193403 . _:b213194458 "2"^^ . _:b213193404 . _:b213193405 . _:b213193406 . _:b213194481 . _:b213193407 . _:b213194469 "2"^^ . _:b213193392 . _:b213193393 . _:b213193652 . _:b213193394 . _:b213193395 . _:b213194468 "2"^^ . _:b213193396 . _:b213193397 . _:b213193398 . _:b213193399 . _:b213194471 "2"^^ . _:b213193352 . _:b213193353 . . _:b213193354 . _:b213193355 . _:b213194470 "2"^^ . _:b213193356 . _:b213193357 . _:b213193358 . _:b213193359 . _:b213194465 "2"^^ . _:b213193344 . _:b213193345 . . _:b213193346 . _:b213193961 . _:b95138 . _:b213194464 "2"^^ . _:b213193347 . _:b213193348 . . _:b213193349 . . _:b213193350 . _:b213193351 . _:b95139 . _:b213194467 "2"^^ . _:b213193368 . _:b213193369 . _:b213193370 . _:b213193371 . _:b213194466 "2"^^ . _:b213193372 . _:b213193373 . . _:b213193374 . _:b213193375 . _:b213194477 "2"^^ . _:b213193360 . . _:b213193361 . _:b213193362 . _:b213193363 . _:b213194476 "2"^^ . . _:b213193364 . _:b213193365 . _:b213193366 . _:b213193367 . _:b213194479 "2"^^ . . _:b213193448 . . _:b213193449 . _:b213193450 . _:b213193451 . _:b213194478 "2"^^ . _:b213193452 . _:b213193453 . _:b213193454 . _:b213193455 . _:b213194473 "2"^^ . . _:b213193440 . _:b213194047 . _:b213193441 . _:b213193442 . _:b213193443 . _:b213194472 "2"^^ . _:b213193444 . _:b213193445 . _:b213193446 . _:b213194421 . _:b213193447 . _:b213194475 "2"^^ . _:b213193464 . _:b213193465 . _:b213193466 . _:b213193467 . _:b213194474 "2"^^ . _:b213193468 . . _:b213193469 . _:b213193470 . _:b213193471 . _:b95161 . _:b213194485 "2"^^ . _:b213193474 . _:b213193456 . _:b213193457 . _:b213193458 . _:b213193459 . _:b213194484 "2"^^ . _:b213193460 . . _:b213193461 . _:b213193462 . _:b213193463 . _:b213194487 "2"^^ . _:b213193416 . _:b213193417 . _:b95185 . _:b213193418 . _:b213193419 . _:b213194486 "2"^^ . _:b213193420 . _:b213193421 . _:b213193422 . _:b213193423 . _:b213194481 "2"^^ . _:b213193408 . _:b213193409 . _:b213193410 . _:b213193411 . _:b213194480 "2"^^ . _:b213193412 . _:b213193413 . _:b213193525 . _:b213193414 . _:b213193415 . _:b213194483 "2"^^ . . _:b213193432 . . _:b213193433 . _:b213193434 . _:b213193435 . _:b213194482 "2"^^ . . _:b213193436 . _:b213193437 . _:b213193438 . _:b213193439 . _:b213194493 "2"^^ . _:b213193424 . _:b213193425 . _:b213193426 . _:b213193427 . _:b213194492 "2"^^ . _:b213193428 . _:b213193429 . _:b213193430 . _:b213193431 . _:b213194495 "2"^^ . . . _:b213194386 . _:b213194494 "2"^^ . . . _:b213193669 . _:b213194489 "2"^^ . . _:b213194488 "2"^^ . _:b213194491 "2"^^ . . _:b213194490 "2"^^ . _:b213194501 "2"^^ . . _:b213194500 "2"^^ . _:b213194503 "2"^^ . _:b213194502 "2"^^ . _:b213193395 . _:b213194497 "2"^^ . _:b213194310 . _:b213194496 "2"^^ . _:b213194036 . _:b213194568 . _:b213194499 "2"^^ . . _:b213194498 "2"^^ . _:b213194509 "2"^^ . _:b213194327 . _:b213194508 "2"^^ . . . _:b213194088 . _:b213194511 "2"^^ . _:b95177 . . _:b213193323 . _:b213194510 "2"^^ . _:b213193324 . _:b213193325 . _:b213193326 . _:b213193327 . _:b213194505 "2"^^ . _:b213193572 . _:b213194504 "2"^^ . _:b213194507 "2"^^ . _:b213193336 . _:b213193337 . _:b213193338 . _:b213193339 . _:b213194506 "2"^^ . _:b213193340 . _:b213193341 . _:b213193342 . _:b213193343 . _:b213194517 "2"^^ . _:b213193328 . _:b213193329 . _:b213193330 . _:b213193331 . _:b213194516 "2"^^ . _:b213193332 . _:b213193333 . _:b213193334 . _:b213193385 . _:b213194519 "2"^^ . _:b213193335 . . _:b213193487 . _:b213193372 . _:b213194518 "2"^^ . . _:b213194513 "2"^^ . _:b213193470 . _:b213193501 . _:b213193587 . _:b213194512 "2"^^ . _:b213193378 . _:b213194515 "2"^^ . . _:b213194514 "2"^^ . _:b213193623 . _:b95128 "The DNA precursor analogue BrdU provides a facile means of labeling DNA in eukaryotic cells (Dolbeare, >>1995<<, 1996). S phase cells grown for 20 min in medium supplemented with BrdU incorporate the analogue into active sites of DNA synthesis (Nakamura et al., 1986)." . _:b213194525 "2"^^ . _:b213194524 "2"^^ . _:b213194527 "2"^^ . _:b213193640 . _:b213194131 . _:b213193641 . . _:b213193642 . _:b213193643 . _:b213194538 . _:b213194526 "2"^^ . _:b213193644 . . _:b213193645 . _:b213193646 . _:b213194552 . _:b213193647 . _:b213194521 "2"^^ . _:b213193632 . . _:b213193633 . _:b213193634 . _:b213193635 . _:b213194520 "2"^^ . _:b213193636 . _:b213193637 . _:b213193638 . _:b213193639 . _:b213194523 "2"^^ . _:b213194125 . _:b213193656 . _:b213193681 . _:b213193657 . _:b213193658 . . _:b213193659 . _:b213194522 "2"^^ . _:b213193660 . _:b213193661 . _:b213193975 . _:b213193595 . _:b213193662 . . _:b213194533 "2"^^ . _:b213193663 . _:b213193648 . _:b213193649 . _:b213193650 . _:b213194429 . _:b213193651 . _:b213194532 "2"^^ . _:b213193527 . _:b213193652 . _:b213193653 . _:b213193654 . . _:b213194535 "2"^^ . _:b213193655 . _:b213193435 . _:b213193608 . _:b213193609 . _:b213193610 . _:b213193611 . _:b213194534 "2"^^ . _:b213193612 . . _:b213193613 . _:b213193536 . _:b213193614 . _:b213193615 . _:b213194529 "2"^^ . _:b213193600 . _:b213193601 . _:b213193602 . . _:b213194528 "2"^^ . _:b213193603 . _:b213193604 . . _:b213194338 . _:b213193605 . _:b213193606 . _:b213193607 . _:b213194531 "2"^^ . _:b213193624 . _:b213193625 . _:b213193626 . _:b213193627 . _:b213194530 "2"^^ . _:b213193628 . _:b213193570 . _:b213193629 . _:b213193630 . _:b213193631 . _:b213194541 "2"^^ . _:b213193616 . _:b213193617 . _:b213193618 . . _:b213193619 . _:b213194540 "2"^^ . _:b213193620 . _:b213193621 . _:b213193622 . _:b213193623 . _:b213194543 "2"^^ . _:b213193704 . _:b213193705 . _:b213193706 . . _:b213194542 "2"^^ . _:b213193707 . _:b213193708 . _:b213193709 . _:b213193710 . _:b213193711 . _:b213194537 "2"^^ . _:b213193696 . . _:b213193697 . _:b213194034 . _:b213193698 . _:b213193699 . _:b213194536 "2"^^ . . _:b213193700 . _:b213193891 . . _:b213193701 . _:b213193702 . _:b213193703 . _:b213194539 "2"^^ . _:b213193720 . _:b213193721 . _:b213193722 . _:b213193723 . _:b213194538 "2"^^ . _:b213193724 . _:b213193725 . _:b213193726 . _:b213194266 . _:b213194549 "2"^^ . _:b213193727 . _:b213193712 . _:b213193713 . _:b213193714 . _:b213193715 . _:b213194548 "2"^^ . . _:b213193716 . _:b213193717 . _:b213193718 . . _:b213194551 "2"^^ . _:b213193719 . . . _:b213193672 . . _:b213193673 . _:b213194272 . _:b213193674 . _:b213193675 . _:b213194550 "2"^^ . _:b213193676 . . _:b213193677 . _:b213193670 . _:b213193678 . _:b213193679 . _:b213194545 "2"^^ . _:b213193664 . _:b213193665 . _:b213193664 . _:b213193666 . _:b213193667 . _:b213194544 "2"^^ . _:b213193668 . _:b213193669 . _:b213193670 . . _:b213194547 "2"^^ . _:b213193671 . _:b213193688 . . _:b213193689 . _:b213193690 . . _:b213194546 "2"^^ . _:b213193691 . _:b213193892 . _:b213193692 . _:b213193693 . _:b213193694 . _:b213194428 . _:b213193695 . _:b213194557 "2"^^ . _:b213193680 . _:b213193681 . . _:b213193682 . _:b213193683 . _:b213194556 "2"^^ . _:b213193684 . _:b213193685 . _:b213193686 . _:b213193687 . _:b213194559 "2"^^ . _:b213193512 . _:b213193513 . _:b213193514 . . _:b213194558 "2"^^ . _:b213193515 . _:b213193516 . _:b213193517 . _:b95188 "This approach allows interphase chromosome domains to be seen using conditions that are much less destructive than those used to visualize chromosome territories by FISH (Schardin et al., 1985; Manuelidis, >>1985<<)." . _:b213193518 . _:b213193519 . _:b213194553 "2"^^ . _:b213193504 . _:b213193505 . _:b213193506 . _:b213193507 . _:b213194552 "2"^^ . _:b213193508 . _:b213193509 . _:b213193510 . _:b213193511 . _:b213194555 "2"^^ . _:b213194499 . _:b213193619 . _:b213193528 . _:b213193529 . . _:b213193530 . _:b213193531 . _:b213194554 "2"^^ . _:b213193532 . _:b213193533 . _:b213194151 . _:b213193534 . _:b213193535 . _:b213194565 "2"^^ . _:b213193520 . _:b213193521 . _:b213193522 . _:b213194304 . _:b213193523 . _:b213194564 "2"^^ . _:b213193524 . _:b95159 "For example, the average extension of an integrated Epstein-Barr virus genome (Lestou et al., >>1996<<) and various Arabidopsis sequences of 4\u201363 kbp (Fransz et al., 1996) were 2.99 kbp/\u03BCm and 3.27 kbp/\u03BCm, respectively." . _:b213194446 . _:b213193525 . _:b213193526 . _:b213193527 . _:b213194567 "2"^^ . _:b213193480 . _:b213193481 . _:b213193482 . _:b213193483 . _:b213194566 "2"^^ . _:b213193824 . _:b213193484 . _:b213193485 . _:b213193486 . _:b213193487 . _:b213194561 "2"^^ . _:b213194113 . _:b213193472 . _:b213193473 . _:b213193854 . _:b95135 "1 F) that presumably arise from the separation of the duplicated DNA soon after synthesis (Selig et al., 1992; Kitsberg et al., >>1993<<). Sister foci first appeared 1 h into S phase (not shown) and remained paired until mitosis (Fig. 1, C and G). As expected, predominantly single foci were seen in the following G1 phase (Fig. 1, D and H)." . _:b213193474 . _:b213193475 . _:b213194560 "2"^^ . _:b213193476 . _:b213193477 . _:b213193478 . _:b213193479 . _:b213194563 "2"^^ . _:b213193496 . . _:b213193497 . _:b213193498 . _:b213193499 . _:b213194562 "2"^^ . _:b213193500 . _:b213193501 . _:b213193502 . _:b213193503 . _:b213194573 "2"^^ . _:b213193488 . _:b213193489 . . _:b213193490 . _:b213193491 . _:b213194572 "2"^^ . _:b213193492 . _:b213193493 . _:b213193494 . _:b213193495 . _:b213194575 "2"^^ . _:b213193576 . _:b213193577 . _:b213193578 . _:b213193579 . _:b213194574 "2"^^ . . _:b213193580 . _:b213193581 . _:b213193499 . _:b213193582 . _:b213193583 . _:b213194569 "2"^^ . _:b213193568 . _:b213193569 . _:b213193570 . _:b213193571 . _:b213194568 "2"^^ . _:b213193572 . . _:b213193573 . _:b213193574 . _:b213193575 . _:b213194571 "2"^^ . _:b213193592 . _:b213193593 . _:b213193594 . _:b213193595 . _:b213194570 "2"^^ . _:b213193596 . _:b213193597 . _:b213193598 . _:b213193599 . _:b213194581 "2"^^ . _:b213193584 . _:b213193585 . _:b213193586 . . _:b213194580 "2"^^ . _:b213193587 . _:b213193588 . _:b213193589 . _:b213193590 . . _:b213194583 "2"^^ . _:b213193591 . _:b213193544 . _:b213193545 . _:b213193546 . _:b213193510 . . _:b213194582 "2"^^ . _:b213193820 . _:b213193547 . . _:b213193548 . _:b213193338 . _:b213193549 . _:b213193550 . . _:b213194577 "2"^^ . _:b213193551 . _:b213193536 . _:b213193537 . . _:b213193538 . _:b213194223 . _:b213193539 . _:b213194576 "2"^^ . _:b213193540 . _:b213193541 . _:b213193542 . _:b95167 . _:b213193543 . _:b213194579 "2"^^ . _:b213194060 . _:b213193560 . _:b213193561 . _:b95148 "Whereas the characteristic appearance of mitotic chromosomes confirms that they are highly organized (Holmquist, 1992), the molecular features responsible remain ill-defined (Earnshaw, >>1988<<; Manuelidis and Chen, 1990; Saitoh and Laemmli, 1994; Cook, 1995). However, different aspects of chromosome structure are known to correlate with nuclear function." . _:b213194033 . _:b213193562 . _:b213193563 . _:b213194578 "2"^^ . _:b213193564 . _:b213193934 . _:b213193565 . _:b213193566 . _:b213193646 . _:b213194589 "2"^^ . _:b213193567 . _:b213193552 . _:b213193963 . . _:b213193553 . _:b213193554 . _:b213193555 . _:b213194588 "2"^^ . _:b213193556 . . _:b213194101 . _:b213193557 . _:b213193558 . _:b213193753 . _:b213194591 "2"^^ . . _:b213193559 . . _:b213194590 "2"^^ . _:b213194585 "2"^^ . _:b95149 . _:b213194584 "2"^^ . _:b213194587 "2"^^ . . _:b213194020 . _:b213194586 "2"^^ . _:b213194597 "2"^^ . _:b213193726 . . _:b213194596 "2"^^ . _:b213194599 "2"^^ . . _:b213194598 "2"^^ . _:b213194593 "2"^^ . . _:b213193584 . _:b213194592 "2"^^ . . _:b213194595 "2"^^ . _:b213194464 . _:b213194594 "2"^^ . _:b213194605 "2"^^ . . _:b213194604 "2"^^ . _:b213194607 "2"^^ . . _:b213194606 "2"^^ . _:b213194601 "2"^^ . _:b213194128 . "PMC0" . _:b213194600 "2"^^ . _:b213193389 . . _:b213194603 "2"^^ . _:b213194602 "2"^^ . . _:b95160 "For example, the average extension of an integrated Epstein-Barr virus genome (Lestou et al., 1996) and various Arabidopsis sequences of 4\u201363 kbp (Fransz et al., >>1996<<) were 2.99 kbp/\u03BCm and 3.27 kbp/\u03BCm, respectively." . _:b213194480 . _:b213194242 . . _:b213194321 . _:b213194609 "2"^^ . _:b213194608 "2"^^ . . _:b213193496 . _:b95154 . _:b213194608 . _:b213194569 . _:b213194319 . _:b213193822 . . . . . . . . _:b213194382 . . _:b213194306 . _:b95190 "Indeed, it may seem remarkable that two sequences separated by 1-Mbp DNA should be \u223C1.5-\u03BCm apart in nuclei (van den Engh et al., 1992; Yokota et al., >>1995<<) when the same sequences folded as a 10-nm chromatin fiber might be separated by as much as \u223C55 \u03BCm (this extent of separation is clearly not possible in a typical human nucleus)." . _:b213193706 . _:b213194371 . _:b213193552 . _:b213193612 . . _:b95141 . _:b213193526 . . . _:b95134 "1 F) that presumably arise from the separation of the duplicated DNA soon after synthesis (Selig et al., >>1992<<; Kitsberg et al., 1993)." . _:b213193450 . _:b213194356 . . . _:b213194407 . . . _:b213194510 . . . . _:b95155 "In mammalian cells, the synchronous activation of groups of contiguous replicons allows the separation of adjacent replicons to be measured (Huberman and Riggs, >>1968<<). Detailed analyses of different mammalian cells suggests that most relicons are 50\u2013300 kbp (for review see Edenberg and Huberman, 1975; Hand, 1978)." . . _:b213193972 . . . _:b213194331 . _:b213194543 . _:b213193521 . _:b213194002 . _:b95125 "DNA fibers were denatured directly (2.5 M HCl, 1 h; 20\u00B0C) and immunostained with mouse anti-BrdU IgG and donkey anti\u2013mouse IgG conjugated with Cy-3, as described above (see also Tomilin et al., >>1993<<)." . . . . _:b95176 "Cell Biol. 115:9a; as discussed in Jackson, 1995b and Berezney et al., 1995a )." . . _:b95180 . _:b213194451 . _:b213193718 . _:b213193758 . . _:b213194383 . _:b213194403 . _:b213193432 . . _:b213193689 . _:b213194028 . _:b213194555 . _:b213194506 . _:b213193864 . . . _:b213194400 . _:b213194220 . _:b213193610 . _:b213194511 . . . _:b213193630 . . . . _:b213194440 . . _:b213194106 . . . _:b213193767 . _:b213194587 . . . . . . . _:b213194139 . . . . . _:b213194312 . _:b213194236 . . . _:b213193719 . _:b213193503 . . _:b213193831 . . . . _:b213193911 . _:b213194296 . _:b213193331 . _:b213193379 . . . . _:b213194029 . _:b95194 "In mammalian cells, this efficiency is difficult to assess as procedures that yield the desired level of cell synchrony alter the natural patterns of origin activation (see Jackson, 1995a for discussion)." . . _:b213193957 . _:b213194486 . _:b213193829 . _:b213194343 . _:b213194408 . _:b213194409 . _:b213194410 . _:b213194411 . _:b213194213 . _:b213194412 . _:b213194413 . _:b213194414 . . _:b213194415 . _:b213194400 . _:b213194401 . _:b213194524 . _:b213194402 . _:b213194403 . _:b213194404 . _:b213194405 . _:b213194406 . _:b213194407 . _:b213194424 . _:b213194425 . _:b213194426 . _:b213194427 . _:b213194428 . _:b213194429 . _:b213194430 . _:b213194431 . _:b213194416 . _:b213194417 . _:b213194418 . . _:b213194419 . _:b213194420 . _:b213194421 . _:b213194422 . _:b213194423 . _:b213194376 . _:b213194148 . _:b213194377 . _:b213194378 . _:b213194379 . . _:b213194380 . _:b213194381 . _:b213194382 . _:b213194383 . . _:b213194368 . . _:b213194369 . _:b213194370 . _:b213194371 . _:b213194372 . _:b213194373 . _:b213194374 . _:b213194375 . . _:b213194392 . _:b213194393 . _:b213194394 . _:b213194395 . _:b213194396 . _:b213194397 . _:b213194398 . _:b213194399 . _:b213194384 . _:b213194385 . _:b213194386 . _:b213194387 . _:b213194388 . . _:b213194389 . . . _:b213194390 . _:b213194391 . . _:b213194472 . _:b213194111 . _:b213194473 . _:b213194474 . _:b213194475 . _:b213194025 . _:b213194476 . _:b213194477 . _:b213193925 . _:b213194478 . _:b213194479 . _:b213194046 . _:b213194464 . _:b213193638 . _:b213194465 . _:b213194466 . _:b213194192 . _:b213194467 . _:b213194468 . _:b213194469 . _:b213194470 . _:b95153 "This distinction implies that elements of the mitotic organization must persist throughout interphase when each chromosome occupies a discrete \u201Cterritory\u201D (Cremer et al., >>1993<<) that provides a reasonably stable environment for chromosome structure (Abney et al., 1997)." . _:b213194471 . _:b213194488 . _:b213194489 . _:b213194490 . _:b213194491 . _:b213194492 . _:b213194493 . _:b213193522 . _:b213194494 . _:b213194495 . _:b213194480 . _:b213194481 . _:b213194482 . _:b213194483 . _:b213194484 . _:b213194485 . _:b213194486 . _:b213194487 . _:b213193559 . _:b213194440 . _:b213194441 . _:b213194237 . _:b213194442 . _:b213194443 . _:b213194444 . _:b213194445 . _:b213193880 . _:b213194446 . _:b213194447 . _:b213194432 . _:b213194433 . _:b213194434 . _:b95134 . . _:b213194435 . _:b213194436 . _:b213194324 . _:b213194437 . _:b213194438 . _:b213193326 . _:b213194439 . _:b213194456 . _:b213194457 . _:b213194458 . _:b213194514 . _:b213194459 . _:b213194460 . _:b213194461 . _:b95119 "materials and methods" . _:b213194462 . _:b213194463 . _:b213194448 . . _:b213194449 . _:b213194450 . _:b213193752 . _:b213194451 . _:b213194452 . _:b213194229 . _:b213194453 . _:b213194454 . _:b213194455 . _:b213194280 . _:b213194281 . _:b213194282 . _:b213194283 . _:b213194284 . _:b213194285 . _:b213193848 . . _:b213194286 . _:b213194287 . _:b213194272 . . _:b213194273 . . _:b213194274 . _:b213194275 . _:b213194276 . _:b213194277 . _:b213194278 . _:b213194279 . _:b213194296 . _:b213194297 . . _:b213194298 . _:b213194299 . _:b213194300 . _:b213194301 . _:b213194302 . _:b213194303 . _:b213193733 "3"^^ . _:b213194288 . _:b213194289 . . . _:b213194290 . _:b213194291 . _:b213194602 . _:b213193732 "3"^^ . _:b213194292 . . _:b213194185 . _:b213194293 . _:b213194018 . _:b213194294 . _:b213194295 . _:b213193735 "3"^^ . _:b213194248 . _:b213194249 . _:b213194250 . _:b213194251 . _:b213193734 "3"^^ . _:b213194252 . _:b213194253 . _:b213193942 . . _:b213194254 . _:b213194255 . _:b213193729 "3"^^ . _:b95126 "Cells or DNA fibers containing both BrdU and IdU were labeled following the approach described by Manders et al. (>>1992<<). DNA was denatured as described above, samples were washed in borate and PBS+, and then incubated (30 min, 20\u00B0C) with 5% normal donkey serum in PBS+, then (1 h, 20\u00B0C) with a rat anti-BrdU IgG (20 \u03BCg/ml; Harlan Sera-lab Ltd.," . _:b213194240 . _:b213194241 . _:b213194242 . _:b213194243 . _:b213193728 "3"^^ . _:b213194244 . . _:b213194308 . _:b213194245 . _:b213193797 . _:b213194246 . _:b213194247 . _:b213193731 "3"^^ . _:b213194264 . _:b213194265 . _:b95179 "Though daughter chromatids (Sumner, >>1991<<) are not resolved until late in prophase, daughter replicons are known to be resolved soon after replication is complete (Selig et al., 1992; Kitsberg et al., 1993)." . _:b213194266 . _:b213194267 . _:b213193730 "3"^^ . _:b213193721 . _:b213194268 . . _:b213194269 . _:b213194270 . _:b213194271 . _:b213193741 "3"^^ . _:b213194256 . _:b213194257 . _:b213194258 . _:b213194259 . _:b213193740 "3"^^ . _:b213194260 . . _:b213194261 . _:b213194262 . _:b213194263 . _:b213193743 "3"^^ . _:b213194344 . _:b213194345 . _:b213194346 . _:b213194347 . _:b213193742 "3"^^ . _:b213194348 . _:b213194349 . _:b213194350 . _:b213194351 . _:b213193737 "3"^^ . _:b213194336 . _:b213194337 . . _:b213194338 . _:b213193418 . _:b213194339 . _:b213193736 "3"^^ . _:b213194340 . _:b213194341 . _:b213194342 . _:b213194343 . _:b213193739 "3"^^ . _:b213194360 . _:b213194361 . . _:b213194362 . . _:b213194363 . _:b213193738 "3"^^ . _:b213194364 . _:b213194365 . _:b213194366 . _:b213194367 . _:b213193749 "3"^^ . _:b213194352 . _:b213194353 . _:b213194354 . . _:b213194355 . _:b213193748 "3"^^ . _:b213194356 . . _:b213193482 . _:b213194357 . _:b213194358 . . _:b213194359 . _:b213193751 "3"^^ . _:b213194463 . _:b213194312 . _:b213194313 . _:b213194445 . _:b213194314 . _:b213194315 . _:b213193750 "3"^^ . _:b213194316 . . _:b213194317 . _:b213194318 . _:b213194193 . _:b213194319 . _:b213193745 "3"^^ . _:b213194304 . _:b213194305 . _:b213194306 . _:b213194307 . _:b213193744 "3"^^ . _:b213194308 . _:b213194309 . _:b213194310 . _:b213194311 . . _:b213194328 . _:b213193747 "3"^^ . _:b213193557 . _:b213194329 . _:b213194330 . _:b213194331 . _:b213193746 "3"^^ . _:b213194332 . _:b213194021 . _:b213194333 . _:b213194334 . _:b213194322 . _:b213194335 . _:b213193367 . _:b213193757 "3"^^ . _:b213194320 . . _:b213194321 . _:b213194322 . _:b213194228 . _:b213194323 . _:b213193756 "3"^^ . _:b213194324 . _:b213194325 . _:b213194326 . _:b213194327 . _:b213193759 "3"^^ . _:b213194425 . _:b213193758 "3"^^ . _:b213193753 "3"^^ . _:b213193752 "3"^^ . . . _:b213193755 "3"^^ . _:b213194070 . . _:b213193754 "3"^^ . _:b213193765 "3"^^ . _:b213193764 "3"^^ . _:b213193788 . _:b213194529 . . _:b213193767 "3"^^ . _:b213193766 "3"^^ . _:b213194550 . _:b213193761 "3"^^ . . . . _:b213193998 . _:b213193760 "3"^^ . _:b213193763 "3"^^ . _:b213193762 "3"^^ . _:b213193773 "3"^^ . _:b213193792 . _:b213193772 "3"^^ . _:b213193575 . _:b213193445 . _:b213193775 "3"^^ . . . _:b213193774 "3"^^ . _:b213193769 "3"^^ . _:b213193768 "3"^^ . . _:b213194083 . . _:b213193771 "3"^^ . . _:b213193770 "3"^^ . _:b95165 . . . _:b213193781 "3"^^ . _:b213194534 . _:b213193780 "3"^^ . _:b213193783 "3"^^ . _:b213194565 . _:b213193782 "3"^^ . . . _:b213193777 "3"^^ . . _:b213193776 "3"^^ . _:b213193912 . _:b95140 "As transcriptionally active genes are known to be replicated early in S phase (Hatton et al., >>1988<<), we wanted to establish if transcription sites and replicon clusters, active at different times of S phase, had any structural features in common." . _:b213193779 "3"^^ . . _:b95156 . _:b213193564 . _:b213194417 . _:b213193778 "3"^^ . _:b213194361 . _:b213193789 "3"^^ . _:b213193853 . _:b213193788 "3"^^ . _:b213194299 . _:b213193791 "3"^^ . _:b213194536 . _:b213194537 . _:b213194538 . . _:b213194539 . _:b213193790 "3"^^ . _:b213194540 . _:b213194541 . _:b213194542 . . _:b213194543 . _:b213193785 "3"^^ . . _:b213194528 . _:b213194529 . _:b213194341 . _:b213194530 . _:b213194531 . _:b213193784 "3"^^ . _:b213194532 . _:b213194533 . . _:b213194534 . _:b213194535 . _:b213193787 "3"^^ . _:b213194552 . _:b213194553 . _:b213194504 . _:b213194554 . _:b213194555 . . _:b213193786 "3"^^ . _:b213194556 . _:b213194557 . _:b213194558 . _:b213194559 . _:b213193797 "3"^^ . _:b213194544 . _:b213194545 . _:b213194546 . _:b213194547 . _:b213193796 "3"^^ . _:b213194548 . _:b213193461 . _:b213194549 . _:b213194550 . _:b95143 "Simple eukaryotic models, notably yeast, have facilitated a detailed description of ARS elements (Marahrens and Stillman, 1996) that define sites where DNA synthesis initiates (Fangman and Brewer, >>1992<<) and shown how these direct a single initiation event at the appropriate time of each cell cycle (Diffley and Cocker, 1992; Cocker et al., 1996)." . . _:b213194551 . _:b213193799 "3"^^ . _:b213194504 . _:b213194505 . . _:b213194506 . _:b213194507 . _:b213193798 "3"^^ . _:b213194508 . _:b213193428 . _:b213194509 . _:b213194510 . _:b213194511 . . _:b213194496 . _:b213193793 "3"^^ . _:b213194497 . _:b213194498 . _:b213194499 . _:b213193792 "3"^^ . _:b213194500 . _:b213193709 . _:b213194501 . _:b213194502 . _:b213194503 . _:b213193795 "3"^^ . _:b213194520 . _:b213194521 . _:b213194522 . _:b213194523 . _:b213193794 "3"^^ . _:b213194524 . _:b213194525 . _:b213194526 . _:b213194527 . _:b213193805 "3"^^ . _:b213194512 . _:b213194513 . _:b213194514 . _:b213194515 . _:b213193804 "3"^^ . _:b213194516 . _:b213194517 . _:b213194518 . _:b213194519 . _:b213193807 "3"^^ . _:b213194600 . _:b213194601 . _:b213194602 . _:b213194603 . _:b95190 . _:b213194248 . _:b213193806 "3"^^ . _:b213194604 . _:b213194605 . _:b213194606 . _:b213194607 . _:b213193801 "3"^^ . _:b213194592 . . _:b213194593 . _:b213194594 . _:b213194595 . _:b213193800 "3"^^ . _:b213194596 . _:b213194597 . _:b213194598 . _:b213194599 . . _:b213193803 "3"^^ . _:b213193802 "3"^^ . . _:b213193813 "3"^^ . _:b213194608 . _:b213193952 . _:b213194609 . _:b213193812 "3"^^ . _:b213194533 . _:b213193815 "3"^^ . _:b213194568 . _:b213194569 . _:b213194570 . _:b213194571 . _:b213193814 "3"^^ . _:b213194572 . _:b213193711 . _:b213194573 . _:b213194574 . . _:b213194575 . . . _:b213194560 . _:b213194297 . _:b213193809 "3"^^ . _:b213194561 . _:b213194562 . _:b213194563 . _:b213193808 "3"^^ . _:b213194564 . _:b213194565 . _:b213194566 . _:b213194567 . . _:b213193811 "3"^^ . _:b213194584 . . _:b213194585 . _:b213194586 . _:b213194587 . _:b213193810 "3"^^ . _:b213194588 . _:b213194589 . _:b213194590 . _:b213194591 . _:b213193659 . _:b213194576 . _:b213193821 "3"^^ . _:b213194577 . _:b213194578 . _:b213194579 . _:b213193820 "3"^^ . _:b213194580 . _:b213194581 . _:b213194582 . _:b213194583 . _:b213193823 "3"^^ . _:b213193896 . _:b213193897 . _:b213193898 . _:b213193899 . _:b213193822 "3"^^ . _:b213193900 . _:b213193901 . . _:b213193902 . _:b213193903 . _:b213193817 "3"^^ . _:b213193888 . _:b213193889 . _:b213193890 . . _:b213193891 . _:b213193816 "3"^^ . _:b213193892 . _:b213193893 . _:b213193894 . _:b213193895 . _:b213193819 "3"^^ . _:b213193912 . _:b213193913 . _:b213193914 . _:b213193915 . _:b213193818 "3"^^ . _:b213193916 . _:b213193917 . _:b213193918 . _:b213193919 . _:b213193829 "3"^^ . _:b213193904 . . _:b213193905 . _:b213193906 . _:b213193907 . _:b213193828 "3"^^ . _:b213193908 . _:b213193909 . _:b213193910 . _:b213193911 . _:b213193831 "3"^^ . . _:b213193864 . _:b213193427 . _:b213193865 . . _:b213193866 . _:b213193867 . _:b213193830 "3"^^ . _:b213193868 . _:b213193869 . _:b213193870 . _:b213193871 . _:b213193825 "3"^^ . _:b213193856 . _:b213193749 . _:b213193857 . _:b213193858 . _:b213194126 . _:b213193859 . _:b213193824 "3"^^ . _:b213193860 . _:b213193861 . _:b213193862 . _:b213193863 . _:b213193827 "3"^^ . _:b213193880 . . _:b213193881 . _:b213193882 . _:b213193883 . _:b213193826 "3"^^ . _:b213193884 . _:b213193885 . _:b213193886 . _:b213193887 . _:b213193452 . _:b213193872 . . _:b213193837 "3"^^ . _:b213194091 . _:b213193873 . _:b213193874 . _:b213193875 . _:b213193836 "3"^^ . _:b213194507 . _:b213193876 . _:b213193654 . . _:b213193877 . _:b213193878 . _:b213193879 . . _:b213193960 . _:b213193839 "3"^^ . _:b213194411 . _:b213193961 . _:b213193962 . _:b213193963 . _:b213193838 "3"^^ . _:b213193964 . _:b213193965 . _:b213193966 . _:b213194420 . _:b213193967 . . _:b213193833 "3"^^ . _:b213193952 . _:b213193953 . _:b213193954 . _:b213193955 . _:b213193938 . _:b213193956 . _:b213193832 "3"^^ . _:b213194239 . _:b213193957 . _:b213193958 . _:b213193959 . _:b213193835 "3"^^ . _:b213193976 . _:b213193977 . _:b213193978 . . _:b213193979 . _:b213193728 . . _:b213193834 "3"^^ . _:b213193980 . _:b213193981 . _:b213193330 . _:b213193982 . _:b213193983 . _:b213194562 . _:b213193845 "3"^^ . _:b213193968 . _:b213193969 . _:b213193970 . _:b213193971 . _:b213194476 . _:b213193844 "3"^^ . _:b213193972 . _:b213193973 . _:b213193974 . _:b213193975 . _:b213193847 "3"^^ . _:b213193928 . _:b213193929 . _:b213193930 . _:b213193931 . _:b213193846 "3"^^ . _:b213193932 . _:b213193933 . _:b213193934 . _:b95120 "Cells were regrown in fresh medium, aphidicolin (5 \u03BCg/ml; Sigma Chemical Co., Poole, UK) was added after 7 h, and cells synchronized at the G1/S border were collected 2 h later (Jackson, 1995a ). In Fig. 6, synchrony was improved using a double thymidine block (2.5 mM thymidine, 24 h; medium, 12 h; 2.5 mM thymidine, 12 h) followed by nocodazole and aphidicolin, as above. This reduces the time cells are held in metaphase," . _:b213193935 . _:b213193841 "3"^^ . _:b213193920 . _:b213193366 . _:b213193921 . _:b213193922 . _:b213193801 . _:b213193923 . _:b213193840 "3"^^ . _:b213193924 . _:b213193925 . _:b213193926 . _:b213193927 . _:b213193843 "3"^^ . _:b213193944 . _:b213193945 . _:b213193946 . _:b213193947 . _:b213193906 . _:b213193842 "3"^^ . _:b213193948 . _:b213193949 . _:b213193964 . _:b213193950 . . _:b213193951 . . _:b213193936 . _:b213193853 "3"^^ . _:b213193937 . _:b213193938 . . _:b213193939 . _:b213193852 "3"^^ . _:b213193940 . _:b213193941 . _:b213194567 . _:b213194330 . _:b213194540 . _:b213193942 . _:b213193943 . _:b213193855 "3"^^ . _:b213193768 . _:b213193769 . _:b213193770 . _:b213194375 . _:b213193771 . . _:b213193854 "3"^^ . . _:b213193772 . . _:b213193773 . _:b213193774 . _:b213193775 . _:b213193849 "3"^^ . _:b213193760 . _:b213193761 . _:b213193762 . _:b213193577 . _:b213193763 . _:b213193848 "3"^^ . _:b213194444 . _:b213193764 . _:b213193765 . _:b213193766 . . _:b213193767 . _:b213193851 "3"^^ . _:b213193784 . _:b213193785 . _:b213193786 . _:b213194373 . _:b213193787 . _:b213193850 "3"^^ . _:b213194593 . _:b213193788 . _:b213193789 . _:b213193790 . . _:b213193791 . . _:b213193861 "3"^^ . _:b213193776 . _:b213193777 . _:b213193778 . _:b213193779 . . _:b213193780 . _:b213193860 "3"^^ . _:b213193781 . _:b213193782 . _:b213194590 . _:b213193783 . _:b213194498 . _:b213193863 "3"^^ . _:b213193736 . _:b213193737 . _:b213193738 . _:b213193739 . _:b213193862 "3"^^ . _:b213193740 . _:b213193741 . _:b213193742 . _:b213193743 . _:b213193857 "3"^^ . _:b213193728 . _:b213193729 . _:b213193939 . _:b213193730 . _:b213193731 . _:b213193856 "3"^^ . _:b95151 . _:b213193732 . _:b213193733 . _:b213193734 . _:b213193735 . _:b213193859 "3"^^ . _:b213193752 . _:b213193753 . _:b213193754 . _:b213193755 . _:b213193858 "3"^^ . _:b213193756 . _:b213193657 . _:b213193757 . _:b213194355 . _:b213193758 . _:b213193759 . _:b213193869 "3"^^ . _:b213193744 . _:b213193745 . _:b213193746 . _:b213193747 . _:b213193868 "3"^^ . _:b213193748 . _:b213193749 . _:b213193750 . _:b213193751 . _:b213193871 "3"^^ . _:b213193832 . _:b213193833 . _:b213193834 . _:b213193835 . _:b213193870 "3"^^ . _:b213193836 . . _:b213193890 . _:b213193837 . _:b213193604 . . _:b213193838 . _:b213193839 . _:b213193865 "3"^^ . _:b213193824 . _:b213193458 . _:b213193825 . _:b213193826 . _:b213193827 . _:b213193864 "3"^^ . _:b213193828 . _:b213193829 . _:b213193830 . . _:b213193831 . _:b213193867 "3"^^ . _:b213193848 . _:b213193769 . _:b213193849 . _:b213193850 . _:b213194495 . _:b213193851 . _:b213193866 "3"^^ . _:b213193852 . _:b213193853 . _:b213193766 . _:b213193854 . _:b213193855 . _:b213193877 "3"^^ . _:b213193840 . _:b213193841 . _:b213193842 . _:b213194527 . _:b213193843 . _:b213193876 "3"^^ . _:b213193844 . _:b213193845 . _:b213193846 . _:b213193847 . _:b213194588 . . _:b213193879 "3"^^ . _:b213193800 . _:b213193801 . _:b213193802 . _:b213193803 . _:b213193878 "3"^^ . _:b213193804 . _:b213193805 . _:b213193806 . _:b213193807 . _:b213193873 "3"^^ . _:b213193792 . . _:b213193793 . _:b213193794 . _:b213193795 . _:b213193872 "3"^^ . _:b213193796 . _:b213193797 . _:b213193798 . _:b213193799 . _:b213193875 "3"^^ . _:b213193816 . _:b213193817 . . _:b213193818 . _:b213193819 . _:b213193874 "3"^^ . _:b213193820 . _:b213193821 . _:b213194104 . _:b213193822 . _:b213193823 . _:b213193885 "3"^^ . _:b213193808 . . _:b213193809 . _:b213193810 . _:b213193811 . _:b213193884 "3"^^ . _:b213193812 . . _:b213193813 . _:b213193814 . _:b213193815 . _:b213193887 "3"^^ . _:b213193625 . _:b213194152 . _:b213193637 . _:b213194153 . _:b213194154 . _:b213194155 . _:b213193886 "3"^^ . _:b213194156 . _:b213194157 . _:b213194100 . _:b213194158 . _:b213194159 . _:b213193881 "3"^^ . _:b213194144 . . _:b213194133 . _:b213194145 . _:b213194243 . _:b213194146 . _:b213194147 . _:b213193880 "3"^^ . _:b213194148 . _:b213193544 . _:b213194149 . _:b213193741 . _:b213194150 . _:b213194151 . _:b213193883 "3"^^ . _:b213194168 . _:b213194169 . _:b213193355 . _:b213194170 . _:b213194171 . _:b213193882 "3"^^ . _:b213194172 . _:b213193947 . _:b213194173 . _:b213194174 . _:b213194175 . _:b213193893 "3"^^ . _:b213194160 . _:b213194161 . _:b213194162 . _:b213194163 . _:b213193892 "3"^^ . _:b213194535 . _:b213194164 . _:b213194165 . _:b213194166 . . _:b213194167 . _:b213193895 "3"^^ . _:b213194120 . _:b213194121 . _:b213194122 . _:b213194123 . _:b213193894 "3"^^ . _:b213194124 . _:b213194125 . _:b213194126 . _:b213194127 . _:b213193889 "3"^^ . _:b213194112 . _:b213194113 . _:b213194114 . _:b213194115 . _:b213193888 "3"^^ . _:b213194116 . . _:b213194117 . _:b213194110 . . _:b213194118 . _:b213193455 . _:b213194119 . _:b213193891 "3"^^ . _:b213194136 . _:b213194137 . _:b213193390 . _:b213194138 . _:b213194139 . _:b213194349 . _:b213194140 . _:b213193890 "3"^^ . . _:b213194141 . . _:b213194142 . _:b213194143 . _:b213193901 "3"^^ . _:b213194128 . . _:b213194129 . _:b213194130 . . _:b213194131 . _:b213193900 "3"^^ . _:b213194132 . _:b213194133 . _:b213194134 . . _:b213194135 . _:b213193907 . _:b213193903 "3"^^ . _:b213194216 . _:b213194217 . _:b213194218 . _:b213194215 . _:b213194219 . _:b213193902 "3"^^ . _:b213194220 . _:b213194221 . _:b213194222 . . _:b213194223 . _:b213193897 "3"^^ . _:b213194208 . _:b213194209 . _:b213194295 . _:b213194210 . _:b213193862 . _:b213194211 . _:b213193398 . _:b213194212 . _:b213193896 "3"^^ . _:b213194213 . _:b213194214 . . _:b213194215 . _:b213193899 "3"^^ . _:b213194232 . _:b213194233 . _:b213194234 . _:b213194235 . _:b213193898 "3"^^ . _:b213194236 . . _:b213194237 . _:b213194238 . _:b213193909 "2"^^ . _:b213194541 . _:b213194239 . _:b213194224 . _:b213194225 . _:b213194226 . _:b213193908 "2"^^ . _:b213194227 . _:b213194228 . _:b213194229 . _:b213194230 . _:b213193911 "2"^^ . _:b213194231 . _:b213194184 . . _:b213194185 . _:b213194186 . _:b213193910 "2"^^ . _:b213194187 . _:b213193364 . _:b213194188 . _:b213193399 . _:b213194189 . _:b213194190 . _:b213193905 "2"^^ . _:b213194191 . _:b213194176 . _:b213194177 . _:b213194178 . . _:b213194179 . . _:b213194180 . _:b213193904 "3"^^ . _:b213194181 . . _:b213194182 . . _:b213193907 "2"^^ . _:b213194183 . _:b213194200 . _:b213194201 . _:b213194202 . _:b213193906 "2"^^ . _:b213194203 . . _:b213194204 . _:b213194205 . _:b213193451 . _:b213194206 . _:b213193917 "2"^^ . _:b213194207 . _:b213194192 . _:b213194193 . _:b213194194 . _:b213193916 "2"^^ . _:b213194195 . _:b213194196 . _:b213194197 . _:b213194198 . _:b213193919 "2"^^ . _:b213194199 . _:b213193962 . _:b213194024 . _:b213194025 . _:b213193492 . _:b213194026 . _:b213193918 "2"^^ . _:b213194027 . . _:b213194028 . . _:b213194029 . _:b213194030 . _:b213193913 "2"^^ . _:b213194031 . _:b213194016 . _:b213194017 . . _:b213194018 . _:b213194519 . _:b213193912 "2"^^ . _:b213194019 . _:b213194020 . _:b213194021 . _:b213194022 . _:b213193915 "2"^^ . . _:b213194023 . _:b213194040 . _:b213194041 . _:b213193405 . _:b213194042 . . _:b213193914 "2"^^ . _:b213194043 . . _:b213194044 . _:b213194045 . _:b213194046 . _:b213193925 "2"^^ . _:b213194047 . _:b213194032 . . _:b213194033 . _:b213194034 . _:b213193924 "2"^^ . _:b213194035 . . _:b213194036 . _:b213194037 . _:b213194038 . _:b213193927 "2"^^ . _:b213194039 . . _:b213193992 . _:b213193993 . . _:b213194408 . _:b213193994 . _:b213193926 "2"^^ . . _:b213193995 . _:b213193996 . _:b213193997 . _:b213193998 . _:b213193921 "2"^^ . _:b213193999 . _:b213193984 . _:b213193985 . _:b213193845 . _:b213193986 . _:b213193920 "2"^^ . _:b213193987 . _:b213193650 . _:b213193988 . _:b213193989 . _:b213193459 . _:b213193990 . _:b213193923 "2"^^ . _:b213193991 . _:b213194008 . _:b213194009 . _:b213194010 . _:b213193922 "2"^^ . _:b213194011 . _:b213194012 . . _:b213194013 . _:b213194003 . _:b213194014 . _:b213193933 "2"^^ . _:b213194015 . _:b213194000 . _:b213194001 . _:b213194002 . _:b213193932 "2"^^ . _:b213194003 . _:b213194004 . _:b213194053 . _:b213194005 . _:b213194006 . _:b213193935 "2"^^ . _:b213194007 . _:b213194088 . _:b213194089 . _:b213194090 . _:b213193934 "2"^^ . _:b213194091 . _:b213194092 . _:b213194093 . _:b213194094 . _:b213193929 "2"^^ . _:b213194095 . _:b213193705 . _:b213194080 . . _:b213194081 . _:b213193506 . _:b213194082 . _:b213193928 "2"^^ . _:b213194083 . _:b213194084 . _:b213194085 . _:b213193533 . _:b213194086 . _:b213193931 "2"^^ . _:b213194087 . _:b213194077 . _:b213194104 . . _:b213194105 . _:b213193768 . _:b213194106 . _:b213193930 "2"^^ . _:b213194107 . _:b213194108 . _:b213194109 . _:b213194110 . _:b213193941 "2"^^ . _:b213194111 . _:b213194096 . . _:b213194097 . _:b213194098 . _:b213193940 "2"^^ . _:b213194099 . _:b213194100 . _:b213194101 . _:b213194102 . _:b213193943 "2"^^ . _:b213194103 . _:b213194056 . _:b213194057 . _:b213194058 . _:b213193942 "2"^^ . _:b213194059 . _:b213194060 . _:b213194061 . _:b213194062 . _:b213193937 "2"^^ . _:b213194063 . _:b213194048 . _:b213193611 . _:b213194049 . _:b213194050 . _:b213193370 . _:b213194051 . _:b213193667 . _:b213193936 "2"^^ . _:b213194052 . _:b213194053 . _:b213194054 . _:b213193939 "2"^^ . _:b213194055 . _:b213194072 . _:b213194073 . _:b213194074 . _:b213193938 "2"^^ . _:b213194075 . _:b213194076 . _:b213194077 . _:b213194078 . _:b213193949 "2"^^ . _:b213194079 . _:b213194064 . _:b213194065 . _:b213194066 . _:b213193948 "2"^^ . _:b213194067 . _:b213194068 . _:b95168 "of the labeled replication sites has been described in detail (Nakamura et al., 1986; Humbert and Usson, 1992; Tomilin et al., 1995), and is known to reflect the natural distribution of replication proteins (Kill et al., 1991; Krude, >>1995<<), ancillary proteins (Leonhardt et al., 1992; Krude, 1995), and particular DNA sequences that replicate at known times of S phase (O'Keefe et al., 1992)." . _:b213194129 . _:b213194069 . _:b213194070 . _:b213193951 "2"^^ . _:b213194071 . _:b213193672 . _:b213194010 . _:b95165 "The appearance of the labeled replication sites has been described in detail (Nakamura et al., 1986; Humbert and Usson, >>1992<<; Tomilin et al., 1995), and is known to reflect the natural distribution of replication proteins (Kill et al., 1991; Krude, 1995), ancillary proteins (Leonhardt et al., 1992; Krude, 1995), and particular DNA sequences that replicate at" . . _:b213193950 "2"^^ . _:b95147 "Whereas the characteristic appearance of mitotic chromosomes confirms that they are highly organized (Holmquist, >>1992<<), the molecular features responsible remain ill-defined (Earnshaw, 1988; Manuelidis and Chen, 1990; Saitoh and Laemmli, 1994; Cook, 1995)." . _:b213193945 "2"^^ . _:b213193944 "2"^^ . _:b213193467 . _:b213193947 "2"^^ . . _:b213194178 . _:b213193946 "2"^^ . _:b213193957 "2"^^ . _:b213193628 . _:b213194090 . _:b213193956 "2"^^ . _:b213194263 . _:b95140 . _:b213193835 . _:b213193959 "2"^^ . . . _:b213193958 "2"^^ . . _:b213193953 "2"^^ . _:b213194164 . _:b213193952 "2"^^ . _:b213194596 . . _:b213193955 "2"^^ . _:b213193954 "2"^^ . _:b213194320 . . . . _:b213193965 "2"^^ . _:b213193964 "2"^^ . _:b213194560 . _:b213193967 "2"^^ . . _:b95181 "Though daughter chromatids (Sumner, 1991) are not resolved until late in prophase, daughter replicons are known to be resolved soon after replication is complete (Selig et al., 1992; Kitsberg et al., >>1993<<). Foci clearly persist into mitosis (Sparvoli et al., 1994), where the expected daughter foci (Baumgartner et al., 1991) can be seen on adjacent chromatid arms (Fig. 1). When nuclei reform after mitosis, the daughter cells contain foci" . _:b213193966 "2"^^ . . _:b213193961 "2"^^ . _:b213194032 . . _:b213193960 "2"^^ . _:b213194199 . . _:b213193963 "2"^^ . _:b213193408 . _:b213193962 "2"^^ . _:b213193973 "2"^^ . _:b213193972 "2"^^ . _:b213193453 . . _:b213193975 "2"^^ . . _:b213194065 . _:b213193974 "2"^^ . . _:b213194485 . _:b213193969 "2"^^ . _:b213194334 . . _:b213193968 "2"^^ . . _:b213193476 . . . . _:b213194423 . _:b213193971 "2"^^ . _:b213193893 . _:b213193649 . _:b213193970 "2"^^ . . _:b213193913 . _:b213193981 "2"^^ . . . . . _:b213193980 "2"^^ . _:b213194099 . _:b213193983 "2"^^ . _:b213193982 "2"^^ . _:b213193456 . . _:b213193977 "2"^^ . _:b213193976 "2"^^ . _:b213193979 "2"^^ . _:b213193978 "2"^^ . _:b213193989 "2"^^ . . _:b213193988 "2"^^ . _:b213193991 "2"^^ . . _:b213193827 . _:b213193990 "2"^^ . _:b213193381 . _:b213193985 "2"^^ . . _:b213193643 . _:b213193984 "2"^^ . _:b213193987 "2"^^ . _:b213194553 . _:b213193986 "2"^^ . _:b213193997 "2"^^ . _:b213193996 "2"^^ . _:b213193999 "2"^^ . _:b95156 "Detailed analyses of different mammalian cells suggests that most relicons are 50\u2013300 kbp (for review see Edenberg and Huberman, >>1975<<; Hand, 1978)." . _:b213193998 "2"^^ . _:b213194145 . . _:b213194419 . _:b213193993 "2"^^ . . . _:b213193992 "2"^^ . _:b213193995 "2"^^ . . _:b213193994 "2"^^ . . _:b213194005 "2"^^ . _:b213193778 . _:b213193433 . _:b213194004 "2"^^ . _:b213194007 "2"^^ . . _:b213194006 "2"^^ . _:b95182 "Foci clearly persist into mitosis (Sparvoli et al., >>1994<<), where the expected daughter foci (Baumgartner et al., 1991) can be seen on adjacent chromatid arms (Fig." . _:b213194001 "2"^^ . _:b213193546 . . _:b213194271 . _:b213194000 "2"^^ . _:b213194003 "2"^^ . _:b213194002 "2"^^ . . . _:b213194013 "2"^^ . _:b213193903 . _:b213193736 . _:b213194012 "2"^^ . _:b213194015 "2"^^ . _:b213194014 "2"^^ . _:b213194009 "2"^^ . . _:b213194008 "2"^^ . . . _:b213194011 "2"^^ . . _:b213194010 "2"^^ . . . _:b213194021 "2"^^ . _:b213194545 . _:b213194020 "2"^^ . _:b213194023 "2"^^ . _:b213194022 "2"^^ . . _:b213194017 "2"^^ . . . _:b213194016 "2"^^ . _:b213194209 . . _:b213194019 "2"^^ . _:b213194018 "2"^^ . _:b213194392 . _:b213194029 "2"^^ . _:b213193509 . _:b213194028 "2"^^ . . _:b213194031 "2"^^ . _:b213194030 "2"^^ . . _:b213194025 "2"^^ . _:b213193787 . _:b213194515 . . _:b213193857 . _:b213194024 "2"^^ . _:b213194027 "2"^^ . . _:b213194026 "2"^^ . _:b213194456 . _:b95186 . _:b213193507 . _:b213194037 "2"^^ . . _:b213194036 "2"^^ . _:b213193984 . . _:b213194039 "2"^^ . . . . _:b213194038 "2"^^ . _:b213194033 "2"^^ . _:b213193866 . . _:b213194032 "2"^^ . _:b213194035 "2"^^ . _:b213194487 . _:b213194034 "2"^^ . . . . . _:b213194045 "2"^^ . _:b213193840 . _:b213193468 . . _:b213194044 "2"^^ . _:b213194416 . _:b213194047 "2"^^ . . _:b213194046 "2"^^ . . . _:b213194041 "2"^^ . _:b213194040 "2"^^ . _:b213193986 . _:b213194043 "2"^^ . . . _:b213194224 . . _:b213194042 "2"^^ . . . _:b213194053 "2"^^ . _:b213193823 . _:b213194214 . _:b213194052 "2"^^ . _:b213194582 . . _:b213194055 "2"^^ . _:b213193999 . . _:b213193773 . _:b213194054 "2"^^ . _:b213194049 "2"^^ . _:b213193518 . _:b213194048 "2"^^ . . . . . . _:b213194051 "2"^^ . _:b213193790 . _:b213194050 "2"^^ . . _:b213194061 "2"^^ . _:b213194060 "2"^^ . _:b213194063 "2"^^ . . _:b213194062 "2"^^ . . _:b213194328 . _:b213194057 "2"^^ . _:b213194056 "2"^^ . _:b213194583 . _:b213194173 . _:b213194059 "2"^^ . _:b213194293 . _:b213193597 . _:b213194058 "2"^^ . . _:b95166 "The appearance of the labeled replication sites has been described in detail (Nakamura et al., 1986; Humbert and Usson, 1992; Tomilin et al., >>1995<<), and is known to reflect the natural distribution of replication proteins (Kill et al., 1991; Krude, 1995), ancillary proteins (Leonhardt et al., 1992; Krude, 1995), and particular DNA sequences that replicate at known times of S phase" . _:b213194069 "2"^^ . . . _:b213194068 "2"^^ . . _:b213194509 . _:b213194071 "2"^^ . _:b213194531 . _:b213194070 "2"^^ . _:b213193683 . _:b213194065 "2"^^ . _:b213194064 "2"^^ . . _:b213194067 "2"^^ . _:b213194359 . _:b213194066 "2"^^ . . . _:b213194077 "2"^^ . _:b213193603 . . . _:b213194076 "2"^^ . _:b213194097 . _:b213193896 . _:b213194079 "2"^^ . _:b213193816 . . _:b213194078 "2"^^ . . . _:b213194073 "2"^^ . _:b213193350 . _:b213194072 "2"^^ . . _:b213194073 . _:b213194075 "2"^^ . . _:b213194074 "2"^^ . _:b213194357 . . _:b213194085 "2"^^ . _:b213194561 . _:b213194084 "2"^^ . _:b213194087 "2"^^ . _:b213193592 . . _:b213194086 "2"^^ . _:b213194081 "2"^^ . _:b213194080 "2"^^ . _:b213193970 . . _:b213194238 . _:b213194083 "2"^^ . . _:b213194082 "2"^^ . _:b213193762 . _:b213194093 "2"^^ . _:b213194092 "2"^^ . _:b213194095 "2"^^ . _:b213194054 . . _:b213194094 "2"^^ . _:b213194589 . _:b213194089 "2"^^ . _:b213193725 . _:b213194088 "2"^^ . _:b213194091 "2"^^ . _:b213193759 . _:b213193991 . _:b213194090 "2"^^ . _:b213194058 . _:b213194184 . . _:b213194101 "2"^^ . . _:b213194100 "2"^^ . _:b213194103 "2"^^ . . _:b213193431 . . . _:b213194102 "2"^^ . _:b213194097 "2"^^ . _:b213194096 "2"^^ . _:b95164 "The appearance of the labeled replication sites has been described in detail (Nakamura et al., >>1986<<; Humbert and Usson, 1992; Tomilin et al., 1995), and is known to reflect the natural distribution of replication proteins (Kill et al., 1991; Krude, 1995), ancillary proteins (Leonhardt et al., 1992; Krude, 1995), and particular DNA" . _:b213194099 "2"^^ . _:b213194098 "2"^^ . . _:b213194532 . _:b213193545 . . _:b213194109 "2"^^ . _:b213194402 . _:b213194108 "2"^^ . _:b213194111 "2"^^ . _:b213194110 "2"^^ . . _:b213194105 "2"^^ . . _:b213194104 "2"^^ . _:b213194107 "2"^^ . _:b213194353 . _:b213194106 "2"^^ . _:b213194117 "2"^^ . _:b213194116 "2"^^ . _:b213194455 . _:b213194019 . _:b213194119 "2"^^ . _:b213194118 "2"^^ . _:b95186 "This dramatic distinction is probably related to the established replication of active genes early in S phase (Hatton et al., >>1988<<) and the stability of replicon clusters active at this time." . _:b213194113 "2"^^ . _:b213193631 . . _:b213194112 "2"^^ . . _:b213194115 "2"^^ . _:b213193899 . _:b213194114 "2"^^ . _:b213194125 "2"^^ . . _:b213194124 "2"^^ . . _:b213194127 "2"^^ . _:b213194126 "2"^^ . _:b95135 . _:b213194121 "2"^^ . _:b213194120 "2"^^ . . _:b95126 . _:b213194123 "2"^^ . _:b213194122 "2"^^ . . _:b213194133 "2"^^ . _:b213194038 . _:b213194132 "2"^^ . _:b213193707 . _:b213194135 "2"^^ . _:b213193573 . _:b213194006 . _:b213194134 "2"^^ . _:b213194129 "2"^^ . . . . _:b213194128 "2"^^ . _:b95124 "washed once in PBS, once in PB (10 mM Na2HPO4, 1 mM MgCl2, 100 mM K-acetate, 30 mM KCl, 1 mM Na2ATP, 1 mM DTT, 0.2 mM PMSF, and 5 units/ml ribonuclease inhibitor (Amersham Intl., Little Chalfont, UK) adjusted to pH 7.4 (Jackson, 1995a ), lysed in PB with 0.25% Triton X-100 (10 min, 0\u00B0C), washed twice in PB, and then extracted with 2 M NaCl (10 min, 0\u00B0C)." . _:b213194131 "2"^^ . _:b213193735 . . _:b213194130 "2"^^ . _:b213193777 . _:b213194141 "2"^^ . _:b213194347 . . _:b213194140 "2"^^ . _:b95127 _:b95136 . _:b213193477 . _:b213193992 . _:b95127 _:b95137 . _:b95127 _:b95138 . _:b95127 _:b95139 . _:b213194143 "2"^^ . _:b95127 _:b95140 . _:b95127 _:b95141 . . _:b213194142 "2"^^ . _:b95127 _:b95128 . _:b95127 _:b95129 . _:b95127 _:b95130 . _:b95127 _:b95131 . _:b213194137 "2"^^ . _:b213193538 . _:b213194484 . _:b95127 _:b95132 . _:b95127 _:b95133 . _:b95127 _:b95134 . _:b95127 _:b95135 . _:b213194136 "2"^^ . _:b213193495 . . _:b213194139 "2"^^ . . . . _:b213194138 "2"^^ . . _:b213194149 "2"^^ . _:b213193579 . _:b213194148 "2"^^ . _:b213194151 "2"^^ . _:b213193373 . _:b213193483 . _:b213194344 . _:b213194150 "2"^^ . _:b213193993 . . _:b213193873 . _:b213194145 "2"^^ . . . _:b213194144 "2"^^ . _:b95119 _:b95120 . _:b95119 _:b95121 . _:b213194042 . _:b95119 _:b95122 . _:b95119 _:b95123 . _:b213194147 "2"^^ . _:b95119 _:b95124 . . _:b95119 _:b95125 . _:b213194342 . _:b95119 _:b95126 . _:b213194146 "2"^^ . _:b213194157 "2"^^ . _:b213194156 "2"^^ . _:b213194159 "2"^^ . _:b213193387 . _:b213194158 "2"^^ . _:b213194153 "2"^^ . _:b213193713 . _:b213194152 "2"^^ . . . _:b213194155 "2"^^ . _:b213194154 "2"^^ . . _:b213193665 . . _:b213194165 "2"^^ . _:b213193549 . . . _:b213194164 "2"^^ . _:b213194167 "2"^^ . _:b213193747 . _:b213194166 "2"^^ . _:b213193358 . _:b213194391 . _:b213194161 "2"^^ . _:b213194160 "2"^^ . _:b213194163 "2"^^ . _:b213194170 . _:b213194284 . . _:b213194162 "2"^^ . _:b213194173 "2"^^ . . . . _:b213193553 . _:b213194172 "2"^^ . . _:b213194175 "2"^^ . . _:b213193609 . _:b213194302 . _:b213194174 "2"^^ . _:b95142 _:b95196 . . . _:b213193930 . _:b95142 _:b95197 . _:b95142 _:b95198 . _:b213194169 "2"^^ . _:b213194387 . _:b213194546 . _:b95142 _:b95192 . _:b95142 _:b95193 . _:b95142 _:b95194 . _:b95142 _:b95195 . _:b213194168 "2"^^ . _:b95142 _:b95188 . _:b95142 _:b95189 . _:b213193868 . _:b95142 _:b95190 . _:b213193335 . . _:b213194171 "2"^^ . _:b95142 _:b95191 . _:b95142 _:b95184 . _:b95142 _:b95185 . . _:b95142 _:b95186 . . _:b213194170 "2"^^ . _:b95142 _:b95187 . _:b95142 _:b95180 . _:b95142 _:b95181 . _:b95142 _:b95182 . _:b95142 _:b95183 . _:b213194181 "2"^^ . _:b95142 _:b95176 . _:b95142 _:b95177 . . _:b95142 _:b95178 . _:b95142 _:b95179 . _:b213194180 "2"^^ . _:b95142 _:b95172 . _:b95142 _:b95173 . . _:b95142 _:b95174 . _:b95142 _:b95175 . _:b213194183 "2"^^ . _:b95142 _:b95168 . _:b95142 _:b95169 . _:b95142 _:b95170 . _:b95142 _:b95171 . _:b213194182 "2"^^ . _:b95142 _:b95164 . . _:b95142 _:b95165 . _:b95142 _:b95166 . _:b95142 _:b95167 . _:b213194177 "2"^^ . _:b95142 _:b95160 . . _:b95142 _:b95161 . _:b213194102 . _:b95142 _:b95162 . _:b95142 _:b95163 . _:b213194176 "2"^^ . _:b95142 _:b95156 . _:b95142 _:b95157 . _:b213194175 . _:b95142 _:b95158 . _:b95142 _:b95159 . _:b213194179 "2"^^ . _:b95142 _:b95152 . _:b95142 _:b95153 . _:b213194116 . _:b95142 _:b95154 . . _:b213194178 "2"^^ . _:b95142 _:b95155 . _:b95142 _:b95148 . _:b95142 _:b95149 . _:b95142 _:b95150 . _:b95142 _:b95151 . _:b213194189 "2"^^ . _:b95142 _:b95144 . _:b213193979 . _:b95142 _:b95145 . _:b95142 _:b95146 . _:b95142 _:b95147 . _:b213194188 "2"^^ . _:b95142 _:b95143 . _:b213194191 "2"^^ . _:b213194427 . . _:b213194190 "2"^^ . . _:b213194185 "2"^^ . _:b213194184 "2"^^ . _:b213194187 "2"^^ . . _:b213194179 . _:b213194186 "2"^^ . _:b213194197 "2"^^ . . _:b213194196 "2"^^ . . _:b213194199 "2"^^ . _:b213194198 "2"^^ . _:b213194193 "2"^^ . . . _:b213194192 "2"^^ . . _:b213194005 . _:b213194079 . _:b213194195 "2"^^ . . _:b213194194 "2"^^ . . _:b213194205 "2"^^ . . _:b95195 . _:b213194204 "2"^^ . . _:b95181 . _:b213194207 "2"^^ . _:b213194206 "2"^^ . . _:b213194201 "2"^^ . _:b213193676 . _:b213194200 "2"^^ . . _:b213194203 "2"^^ . _:b213193937 . _:b213194202 "2"^^ . _:b213194213 "2"^^ . _:b213193515 . _:b213193621 . _:b213193344 . _:b213194212 "2"^^ . _:b213194215 "2"^^ . _:b213194214 "2"^^ . . _:b213194209 "2"^^ . _:b213194208 "2"^^ . _:b213194211 "2"^^ . _:b95176 . _:b213194210 "2"^^ . . _:b213194221 "2"^^ . _:b213193879 . _:b213194220 "2"^^ . _:b213193520 . _:b213194223 "2"^^ . . _:b213194222 "2"^^ . _:b213194217 "2"^^ . . _:b213194095 . _:b213194216 "2"^^ . . . . _:b213194219 "2"^^ . _:b213194218 "2"^^ . _:b213194221 . _:b213194098 . _:b213194229 "2"^^ . . . . _:b213194228 "2"^^ . _:b213194231 "2"^^ . . _:b213194339 . . _:b213194230 "2"^^ . _:b213194225 "2"^^ . _:b213194224 "2"^^ . _:b213193645 . _:b213193995 . _:b213194166 . _:b213193386 . _:b213194227 "2"^^ . _:b213194226 "2"^^ . _:b213194405 . _:b213194237 "2"^^ . _:b213194288 . . _:b213194236 "2"^^ . _:b213194285 . _:b213194239 "2"^^ . _:b213194238 "2"^^ . _:b213194049 . _:b213194233 "2"^^ . . _:b213194232 "2"^^ . . _:b95187 . . _:b213194235 "2"^^ . _:b213194234 "2"^^ . _:b213193941 . _:b213193571 . _:b213194222 . . . . _:b213194370 . _:b213193588 . _:b213194397 . . _:b213194432 . _:b213193740 . . _:b213193576 . . _:b213193383 . . . _:b213194026 . . . _:b213194249 . _:b95130 "S phase cells grown for 20 min in medium supplemented with BrdU incorporate the analogue into active sites of DNA synthesis (Nakamura et al., >>1986<<). Samples immunostained immediately show (Fig. 1 A) the distribution of active replication sites or foci. HeLa cells synchronized at the S phase border using aphidicolin (Jackson, 1995a ) incorporated BrdU into 749 \u00B1 154 (n = 50)" . _:b213193882 . _:b213193550 . _:b213193693 . _:b213193927 . _:b213193838 . _:b95150 "the characteristic appearance of mitotic chromosomes confirms that they are highly organized (Holmquist, 1992), the molecular features responsible remain ill-defined (Earnshaw, 1988; Manuelidis and Chen, 1990; Saitoh and Laemmli, >>1994<<; Cook, 1995). However, different aspects of chromosome structure are known to correlate with nuclear function." . . _:b213194517 . . . _:b213194120 . _:b213194250 . . _:b213193996 . _:b213193498 . . . _:b213193832 . . _:b213193798 . . . _:b213193920 . . . _:b213193629 . . . _:b213193616 . . . _:b213193904 . . . _:b213194483 . . . _:b213193400 . . _:b213193513 . _:b213194491 . _:b213193744 . _:b213194539 . . . _:b213194181 . . _:b213194424 . _:b213194270 . . _:b213193614 . _:b213193813 . . . _:b213193684 . _:b213194439 . _:b213194477 . . . . _:b213193717 . . _:b213193733 . . . _:b213194376 . . . _:b213193742 . _:b213193620 . _:b213194352 . _:b213193481 . . . _:b213193687 . _:b95167 "appearance of the labeled replication sites has been described in detail (Nakamura et al., 1986; Humbert and Usson, 1992; Tomilin et al., 1995), and is known to reflect the natural distribution of replication proteins (Kill et al., >>1991<<; Krude, 1995), ancillary proteins (Leonhardt et al., 1992; Krude, 1995), and particular DNA sequences that replicate at known times of S phase (O'Keefe et al., 1992)." . . _:b213194241 . _:b213194501 . _:b213194500 . . _:b213194503 . _:b213194502 . _:b213194497 . . _:b213194496 . _:b213194303 . _:b213194499 . . _:b213194498 . _:b213193636 . _:b213193342 . _:b213193704 . _:b213194509 . _:b213194508 . . _:b213194511 . . _:b213194510 . _:b213193523 . _:b213194505 . _:b213194504 . _:b213194507 . _:b213193945 . _:b213193814 . _:b213194467 . _:b213194522 . _:b213194506 . . . _:b213194517 . _:b213193447 . _:b213194516 . _:b213194379 . _:b213194519 . _:b213193472 . _:b213194518 . _:b213194513 . _:b213194512 . _:b213194515 . _:b213193324 "22"^^ . _:b213193327 "20"^^ . _:b213194514 . _:b213193325 "22"^^ . _:b213193326 "20"^^ . _:b213194525 . _:b213193349 . _:b213193329 "20"^^ . _:b213194524 . _:b213193328 "20"^^ . _:b213193471 . . _:b213194527 . . . . _:b213194526 . _:b213193330 "18"^^ . . . _:b213193331 "17"^^ . _:b213194521 . . _:b213193332 "17"^^ . _:b213194520 . . _:b213193333 "17"^^ . _:b213194523 . _:b213193334 "16"^^ . _:b213194522 . _:b213193323 "30"^^ . _:b213193335 "16"^^ . _:b213194533 . _:b213194187 . _:b213193336 "16"^^ . _:b213193343 "13"^^ . _:b95160 . _:b213194532 . . _:b213193337 "15"^^ . . _:b213194535 . _:b213193342 "13"^^ . _:b213193340 . _:b213193338 "15"^^ . _:b213194534 . _:b213193339 "14"^^ . . _:b213194529 . _:b213193340 "14"^^ . _:b213194124 . _:b213193936 . _:b213194528 . _:b213193341 "14"^^ . . _:b213194531 . . _:b95133 . . _:b213194530 . . _:b213194541 . _:b213193351 "12"^^ . . _:b213194540 . _:b213194008 . _:b213193350 "12"^^ . _:b213194543 . . _:b213193349 "12"^^ . _:b213194542 . _:b213193802 . _:b213193348 "12"^^ . . _:b213194537 . _:b213193922 . _:b213193897 . _:b213193347 "12"^^ . _:b213194146 . _:b95132 "Individual replication sites are only active for about 1 h (Nakamura et al., >>1986<<) before adjacent sites are activated. However, labeling with BrdU in vivo allows the distribution of replicons labeled during any interval of S phase to be visualized in any subsequent cell cycle phase (Sparvoli et al., 1994)." . _:b213194536 . _:b213193346 "12"^^ . . _:b213194539 . _:b213193345 "12"^^ . . _:b213194538 . _:b213193344 "13"^^ . _:b213194549 . _:b213193359 "11"^^ . _:b95123 . _:b213194548 . _:b213193358 "11"^^ . . _:b213194551 . _:b213193357 "11"^^ . . _:b213194550 . . _:b213193356 "11"^^ . _:b213194545 . . _:b213193355 "11"^^ . _:b213194465 . _:b213194544 . _:b213193354 "11"^^ . _:b213194547 . _:b213194218 . _:b213193661 . _:b213193353 "12"^^ . . _:b213194546 . _:b213193352 "12"^^ . _:b213194557 . _:b213194156 . _:b213193367 "10"^^ . . _:b213194556 . . _:b213193366 "10"^^ . _:b213194559 . _:b213193365 "10"^^ . _:b213193410 . _:b213194558 . . _:b213193364 "10"^^ . _:b213194553 . _:b213193363 "10"^^ . . _:b213194552 . _:b213193362 "10"^^ . _:b213194311 . _:b213194555 . _:b213193361 "11"^^ . _:b213194554 . _:b213193360 "11"^^ . . _:b213194565 . _:b95169 "in detail (Nakamura et al., 1986; Humbert and Usson, 1992; Tomilin et al., 1995), and is known to reflect the natural distribution of replication proteins (Kill et al., 1991; Krude, 1995), ancillary proteins (Leonhardt et al., >>1992<<; Krude, 1995), and particular DNA sequences that replicate at known times of S phase (O'Keefe et al., 1992)." . _:b213194096 . . _:b213194564 . _:b213193422 . _:b213193374 "9"^^ . _:b213193375 "9"^^ . _:b213194567 . _:b95127 "results" . _:b213194132 . _:b213193372 "9"^^ . _:b213194566 . _:b213194163 . _:b213194367 . _:b213194121 . _:b213193373 "9"^^ . _:b213194561 . _:b213193370 "9"^^ . _:b213194560 . _:b213193371 "9"^^ . _:b213194563 . _:b213193369 "10"^^ . _:b213193599 . . _:b213194562 . _:b213193368 "10"^^ . _:b213194167 . _:b213194573 . _:b213193382 "8"^^ . _:b213194572 . _:b213193383 "8"^^ . _:b213193850 . _:b213194575 . _:b213193380 "9"^^ . _:b213194574 . . _:b95136 . _:b213194183 . _:b213194569 . _:b213193381 "9"^^ . . _:b213193378 "9"^^ . _:b213194568 . _:b213193379 "9"^^ . _:b213194571 . . _:b213193348 . _:b213194063 . _:b213194570 . _:b213193376 "9"^^ . _:b213193757 . _:b213194017 . _:b213194581 . _:b213193377 "9"^^ . . _:b213193390 "8"^^ . _:b213194580 . _:b213193391 "8"^^ . _:b213194583 . . _:b213193388 "8"^^ . _:b213194582 . _:b213194144 . _:b213193389 "8"^^ . . . _:b213194577 . . _:b213193386 "8"^^ . . _:b213194576 . _:b213193387 "8"^^ . _:b213194579 . _:b213193384 "8"^^ . _:b213194578 . _:b213193385 "8"^^ . _:b213194589 . _:b213193398 "7"^^ . _:b213194588 . _:b213193399 "7"^^ . _:b213194142 . _:b213194591 . _:b213193396 "8"^^ . . _:b213194590 . _:b95184 . . _:b213193397 "8"^^ . _:b213194585 . _:b213193423 . _:b213193394 "8"^^ . _:b213194584 . _:b213193825 . . _:b213193794 . _:b213193395 "8"^^ . _:b213194587 . _:b213193494 . _:b213193392 "8"^^ . _:b213194586 . _:b213193393 "8"^^ . _:b213194597 . . _:b213193406 "7"^^ . _:b213194596 . _:b213193407 "7"^^ . _:b213194599 . _:b213193404 "7"^^ . _:b213194598 . _:b213193405 "7"^^ . _:b213193988 . _:b213194593 . _:b213193402 "7"^^ . . _:b213194592 . _:b213193403 "7"^^ . _:b213194216 . _:b213194595 . . _:b213193400 "7"^^ . _:b213194594 . _:b213193369 . _:b213193401 "7"^^ . . _:b213194605 . _:b213193394 . _:b213193414 "7"^^ . _:b213193608 . _:b213194604 . . _:b213193415 "7"^^ . _:b213194607 . _:b213193412 "7"^^ . _:b213193898 . _:b213194606 . _:b213193413 "7"^^ . _:b213194092 . _:b213194601 . _:b213193410 "7"^^ . _:b95175 . _:b213194600 . _:b213193411 "7"^^ . _:b213194603 . _:b213193408 "7"^^ . _:b213194602 . _:b213193409 "7"^^ . _:b213193422 "7"^^ . _:b213193423 "6"^^ . _:b213193596 . _:b213193951 . _:b213193420 "7"^^ . . _:b213193421 "7"^^ . _:b213194609 . _:b213193418 "7"^^ . _:b213194084 . _:b213194608 . _:b213194449 . _:b213193419 "7"^^ . _:b95182 . . . _:b213193416 "7"^^ . . _:b213193417 "7"^^ . _:b213193737 . _:b213193430 "6"^^ . . _:b213193431 "6"^^ . _:b213194198 . _:b213193428 "6"^^ . . _:b213193429 "6"^^ . _:b213193540 . _:b213193426 "6"^^ . _:b213194137 . . _:b213193427 "6"^^ . _:b213193424 "6"^^ . _:b213194031 . _:b213193425 "6"^^ . . _:b213193438 "6"^^ . _:b95178 . _:b213193439 "6"^^ . _:b213193682 . _:b213193436 "6"^^ . _:b213193437 "6"^^ . . _:b213194103 . _:b213193434 "6"^^ . . _:b213193435 "6"^^ . _:b213193432 "6"^^ . . _:b213194369 . _:b213193433 "6"^^ . . _:b213194177 . _:b213193446 "6"^^ . _:b213193447 "6"^^ . . _:b213193444 "6"^^ . _:b213193445 "6"^^ . _:b213193442 "6"^^ . _:b213193443 "6"^^ . . _:b213193440 "6"^^ . _:b213193441 "6"^^ . _:b213193454 "6"^^ . _:b213193455 "6"^^ . _:b213193452 "6"^^ . . _:b213193453 "6"^^ . _:b213194502 . _:b213193450 "6"^^ . _:b213193451 "6"^^ . _:b213193448 "6"^^ . . _:b213193449 "6"^^ . _:b213194203 . . _:b213193462 "6"^^ . _:b213193463 "6"^^ . _:b213193460 "6"^^ . _:b213193461 "6"^^ . _:b213193791 . _:b95195 "As synthesis progresses, secondary sites are activated adjacent to the primary ones (Manders et al., >>1992<<, 1996; Berezney et al., 1995b ), and in clusters that are activated at different times, but that contain replicons activated together (Fig." . _:b213194262 . _:b213193458 "6"^^ . . _:b213193459 "6"^^ . _:b213193456 "6"^^ . _:b213193457 "6"^^ . . . _:b213193469 "5"^^ . . _:b213193852 . _:b213193468 "5"^^ . . _:b213194337 . _:b213193471 "5"^^ . _:b213193470 "5"^^ . _:b213194508 . _:b213193465 "5"^^ . . _:b213193464 "5"^^ . _:b213193467 "5"^^ . _:b213193466 "5"^^ . . _:b213193353 . _:b213193477 "5"^^ . . _:b213193476 "5"^^ . _:b213193479 "5"^^ . _:b213193396 . . _:b213193478 "5"^^ . _:b213193473 "5"^^ . _:b213193472 "5"^^ . _:b213193475 "5"^^ . _:b213193716 . _:b213193474 "5"^^ . _:b213193485 "5"^^ . . _:b213193484 "5"^^ . _:b213193487 "5"^^ . _:b213193859 . _:b213193486 "5"^^ . . . _:b213194579 . _:b213193481 "5"^^ . _:b213193805 . . _:b213193480 "5"^^ . . _:b213193483 "5"^^ . . _:b213193482 "5"^^ . _:b213193488 . _:b213193493 "5"^^ . . _:b213193644 . . _:b213193492 "5"^^ . _:b213193495 "5"^^ . _:b213193494 "5"^^ . _:b213194287 . _:b213194247 . _:b213193489 "5"^^ . _:b213193488 "5"^^ . _:b213194581 . _:b213193491 "5"^^ . . _:b213193490 "5"^^ . _:b213193501 "5"^^ . _:b213193500 "5"^^ . _:b213193503 "5"^^ . . _:b213193534 . _:b213193502 "5"^^ . _:b213193497 "5"^^ . _:b213194089 . _:b213193496 "5"^^ . . _:b213194275 . _:b213194401 . _:b213193499 "5"^^ . _:b213193475 . . . _:b213193498 "5"^^ . _:b213193509 "5"^^ . . _:b213193508 "5"^^ . _:b213193511 "5"^^ . _:b213193915 . _:b213193510 "5"^^ . _:b213193908 . _:b213193505 "5"^^ . _:b213193565 . _:b213193504 "5"^^ . _:b213193507 "5"^^ . _:b213194016 . _:b213193506 "5"^^ . . _:b213193517 "5"^^ . . _:b213193516 "5"^^ . _:b213193519 "5"^^ . _:b213194196 . _:b213193518 "5"^^ . . . _:b213193513 "5"^^ . _:b213193512 "5"^^ . . _:b213193515 "5"^^ . _:b213194340 . _:b213193902 . _:b213194188 . _:b213193514 "5"^^ . _:b213193323 . _:b213193525 "4"^^ . _:b213193524 "4"^^ . . . . _:b213193527 "4"^^ . _:b213194082 . _:b213193526 "4"^^ . . . _:b213193521 "5"^^ . . _:b213193520 "5"^^ . _:b213193523 "4"^^ . _:b213193522 "4"^^ . _:b213193533 "4"^^ . _:b213194231 . . . _:b213193532 "4"^^ . _:b213193535 "4"^^ . _:b213193731 . _:b213193534 "4"^^ . _:b213194315 . _:b213193529 "4"^^ . _:b213193528 "4"^^ . _:b213194603 . . _:b213193531 "4"^^ . _:b213193530 "4"^^ . . _:b213193541 "4"^^ . _:b213193540 "4"^^ . . _:b213193723 . . . _:b213193543 "4"^^ . _:b213193542 "4"^^ . . _:b213193537 "4"^^ . _:b213193536 "4"^^ . _:b213193660 . . _:b213194276 . . _:b213193539 "4"^^ . _:b95173 "Once labeled, replication foci also present a useful tool for the analysis of genome organization (for review see Drouin et al., 1994; Dolbeare, >>1996<<). For example, human lymphocytes labeled with BrdU for 15 min give rise to mitotic chromosomes that appear labeled at discrete sites (e.g., Vogel et al., 1989). Indeed, as labeled replication foci appear to survive mitosis and persist" . . _:b213193538 "4"^^ . _:b213193549 "4"^^ . . _:b213194318 . _:b213193548 "4"^^ . _:b213193551 "4"^^ . _:b213194490 . _:b213193550 "4"^^ . . _:b213193545 "4"^^ . _:b213193985 . _:b213193544 "4"^^ . _:b213193722 . . _:b213193547 "4"^^ . _:b213193546 "4"^^ . . _:b213193557 "4"^^ . . _:b213193556 "4"^^ . _:b95146 . . _:b213193559 "4"^^ . _:b213193558 "4"^^ . _:b213193553 "4"^^ . . _:b213193552 "4"^^ . . _:b213193555 "4"^^ . _:b213194268 . . _:b213193516 . _:b213193554 "4"^^ . _:b213194245 . _:b213194426 . . _:b213193565 "4"^^ . _:b213194244 . _:b213193334 . . _:b213194489 . _:b213193564 "4"^^ . _:b213194247 . . _:b213194225 . _:b213193567 "4"^^ . _:b213194246 . _:b213193566 "4"^^ . _:b213194241 . _:b95154 "elements of the mitotic organization must persist throughout interphase when each chromosome occupies a discrete \u201Cterritory\u201D (Cremer et al., 1993) that provides a reasonably stable environment for chromosome structure (Abney et al., >>1997<<)." . _:b213193561 "4"^^ . _:b213194240 . _:b213193560 "4"^^ . . _:b213194243 . . _:b213193563 "4"^^ . _:b213194242 . _:b213193562 "4"^^ . _:b213194253 . _:b95192 . . _:b213193573 "4"^^ . _:b213194252 . _:b213193572 "4"^^ . _:b213194255 . . _:b213193575 "4"^^ . _:b213194254 . . _:b213193574 "4"^^ . _:b213194249 . . _:b213193569 "4"^^ . _:b213194248 . . . _:b213193714 . _:b213193568 "4"^^ . _:b213194251 . _:b213193633 . _:b213193571 "4"^^ . . _:b213194250 . _:b213193570 "4"^^ . _:b213194261 . _:b213193581 "4"^^ . _:b213193810 . _:b213194260 . . _:b213193580 "4"^^ . . _:b213194263 . _:b213194280 . _:b213193583 "4"^^ . _:b213194262 . _:b95188 . _:b213193582 "4"^^ . _:b213193940 . _:b213194257 . . . . _:b213193577 "4"^^ . _:b213194256 . . _:b213193576 "4"^^ . _:b213194259 . _:b213193579 "4"^^ . _:b213194258 . _:b95191 . _:b213193578 "4"^^ . _:b213194269 . . _:b213193589 "4"^^ . . _:b213194268 . _:b213194189 . . _:b213193588 "4"^^ . _:b213194271 . . . _:b213193591 "4"^^ . _:b213194270 . _:b213193914 . _:b213193590 "4"^^ . _:b213194265 . _:b213193585 "4"^^ . _:b213193849 . _:b213194264 . _:b213193584 "4"^^ . _:b213194267 . _:b213193587 "4"^^ . _:b213194266 . _:b213193586 "4"^^ . _:b213193586 . _:b213194277 . . _:b213193597 "4"^^ . _:b213193601 . _:b213194276 . _:b213194059 . . _:b213193596 "4"^^ . _:b213194044 . _:b213194279 . _:b213194574 . _:b213193599 "4"^^ . . . _:b213194278 . . . _:b213193598 "4"^^ . _:b213194273 . . _:b213193593 "4"^^ . _:b213194272 . _:b213193699 . _:b213193592 "4"^^ . _:b213194275 . . _:b213193595 "4"^^ . . . . _:b213194274 . _:b213193594 "4"^^ . _:b213194285 . _:b213193605 "4"^^ . _:b95144 "elements (Marahrens and Stillman, 1996) that define sites where DNA synthesis initiates (Fangman and Brewer, 1992) and shown how these direct a single initiation event at the appropriate time of each cell cycle (Diffley and Cocker, >>1992<<; Cocker et al., 1996)." . _:b213193412 . _:b213194284 . _:b213193604 "4"^^ . . _:b213194050 . _:b213194287 . _:b213193607 "4"^^ . _:b213194286 . _:b213193606 "4"^^ . _:b213194281 . _:b213193601 "4"^^ . _:b213194280 . _:b213193826 . _:b213193600 "4"^^ . _:b213194412 . . . _:b213194283 . _:b213193603 "4"^^ . _:b213194282 . _:b213193949 . _:b213193602 "4"^^ . _:b213194293 . . _:b213194454 . _:b213193613 "4"^^ . _:b213194292 . _:b95193 "In S. cerevisiae, different ARS elements are activated with different efficiency\u2014some are used each S phase in almost all cells, and others used rarely (Fangman and Brewer, >>1992<<). In mammalian cells, this efficiency is difficult to assess as procedures that yield the desired level of cell synchrony alter the natural patterns of origin activation (see Jackson, 1995a for discussion)." . _:b213193612 "4"^^ . _:b213194295 . _:b213193615 . _:b213193615 "4"^^ . _:b213194294 . _:b213193614 "4"^^ . . _:b213194289 . _:b213193609 "4"^^ . _:b213194230 . _:b213194288 . . _:b213193608 "4"^^ . _:b213194291 . _:b213193611 "4"^^ . _:b213194130 . _:b213194290 . _:b213193610 "4"^^ . . _:b213194301 . . _:b213193621 "4"^^ . . _:b213194300 . . _:b213193620 "4"^^ . _:b213194303 . _:b213193623 "4"^^ . _:b213194435 . _:b213194302 . _:b213193622 "4"^^ . _:b213194297 . _:b213193834 . . _:b213193617 "4"^^ . . _:b213193817 . _:b213194296 . . _:b213193616 "4"^^ . _:b213194299 . _:b213193619 "4"^^ . _:b213194298 . _:b213193618 "4"^^ . . _:b213194309 . _:b213193629 "4"^^ . _:b213194308 . _:b213193628 "4"^^ . _:b213194311 . _:b213194441 . _:b213193631 "4"^^ . _:b213194310 . _:b213193630 "4"^^ . _:b213194305 . _:b213194584 . _:b213193625 "4"^^ . _:b213194304 . . _:b213193624 "4"^^ . _:b213194307 . _:b213193627 "4"^^ . . _:b213194306 . _:b213193626 "4"^^ . _:b213194317 . _:b213193637 "4"^^ . _:b213194316 . _:b213194437 . _:b213193636 "4"^^ . . _:b213194319 . _:b213193639 "4"^^ . _:b213194318 . _:b213193638 "4"^^ . _:b213194227 . _:b213194313 . . _:b213193633 "4"^^ . _:b213194312 . . _:b213193632 "4"^^ . _:b213194315 . . _:b213193635 "4"^^ . _:b213194314 . _:b95162 "It is a routine matter to label sites of replication using BrdU, a DNA precursor analogue that can be detected after incorporation into nascent DNA (for review see Dolbeare, >>1995<<, 1996). The appearance of the labeled replication sites has been described in detail (Nakamura et al., 1986; Humbert and Usson, 1992; Tomilin et al., 1995), and is known to reflect the natural distribution of replication proteins (Kill et" . _:b213193680 . _:b213193634 "4"^^ . _:b213194325 . _:b213193645 "4"^^ . _:b213193958 . _:b213194324 . . _:b213193644 "4"^^ . _:b213194327 . . _:b213193647 "3"^^ . _:b213194326 . _:b213193646 "4"^^ . _:b213194321 . _:b213194251 . _:b213193641 "4"^^ . . _:b213194320 . . _:b213193956 . _:b213193640 "4"^^ . . . _:b213194323 . _:b213193643 "4"^^ . . . _:b213194322 . . _:b213194586 . _:b213193642 "4"^^ . _:b213193843 . _:b213194333 . _:b213193653 "3"^^ . _:b213193745 . _:b213194332 . _:b213193652 "3"^^ . _:b213194335 . _:b213193655 "3"^^ . _:b213194334 . . _:b213193651 . _:b213194007 . _:b213193654 "3"^^ . _:b213193871 . . _:b213194329 . . . _:b213193649 "3"^^ . . _:b213194328 . _:b213193648 "3"^^ . _:b213194331 . _:b213193876 . . _:b213193651 "3"^^ . . . _:b213194330 . _:b95174 "For example, human lymphocytes labeled with BrdU for 15 min give rise to mitotic chromosomes that appear labeled at discrete sites (e.g., Vogel et al., >>1989<<). Indeed, as labeled replication foci appear to survive mitosis and persist throughout the subsequent cell cycle, this approach provides an opportunity to analyze how certain aspects of nuclear structure and function might be linked" . _:b213193650 "3"^^ . _:b213193357 . . . _:b213194341 . _:b213193661 "3"^^ . _:b213194340 . _:b213194609 . . _:b213193660 "3"^^ . . _:b213194343 . _:b213193663 "3"^^ . _:b213193885 . _:b213194342 . _:b213193662 "3"^^ . _:b213193997 . _:b213194337 . _:b213193657 "3"^^ . _:b213194336 . _:b213193656 "3"^^ . _:b213194339 . . _:b213193659 "3"^^ . _:b213194338 . _:b213193658 "3"^^ . _:b213194349 . _:b213194462 . _:b213193669 "3"^^ . _:b213194348 . _:b213193668 "3"^^ . _:b213194316 . _:b213194351 . _:b213193671 "3"^^ . _:b213194350 . _:b213193670 "3"^^ . . _:b213194345 . . . _:b213193665 "3"^^ . _:b213194344 . _:b213194606 . _:b213193664 "3"^^ . _:b213194347 . _:b213193667 "3"^^ . . . _:b213194346 . . . _:b213193666 "3"^^ . _:b213194357 . _:b213193677 "3"^^ . _:b213194388 . _:b213194356 . _:b213194112 . _:b213193676 "3"^^ . _:b213194359 . _:b213193679 "3"^^ . _:b213194358 . _:b213193678 "3"^^ . _:b213194353 . _:b213193673 "3"^^ . _:b213194265 . _:b213194592 . _:b213194352 . . _:b213193672 "3"^^ . . _:b213193695 . _:b213194355 . _:b213193675 "3"^^ . _:b213194354 . . _:b213193674 "3"^^ . _:b213194080 . _:b213194365 . _:b213193738 . _:b213193685 "3"^^ . _:b213194364 . _:b213193426 . _:b213193684 "3"^^ . _:b95171 . _:b213194367 . _:b213193687 "3"^^ . _:b213194366 . _:b213193686 "3"^^ . _:b213194212 . _:b213194361 . . _:b213193681 "3"^^ . _:b213194360 . _:b213193680 "3"^^ . . _:b213193473 . _:b213194363 . _:b213193683 "3"^^ . . _:b213194362 . _:b213193682 "3"^^ . . _:b213193978 . _:b213194373 . . _:b213193693 "3"^^ . _:b213194372 . . . _:b213193692 "3"^^ . . _:b213194375 . _:b213193695 "3"^^ . _:b213194374 . . _:b213194393 . _:b213193694 "3"^^ . _:b213194369 . _:b213193689 "3"^^ . _:b213194554 . _:b213194368 . _:b213193931 . _:b213193841 . _:b213193688 "3"^^ . . _:b213194371 . _:b213193691 "3"^^ . _:b213194370 . . _:b213193690 "3"^^ . _:b213194381 . _:b213193663 . _:b213193701 "3"^^ . _:b213194380 . _:b213193700 "3"^^ . . _:b213194383 . . _:b213193703 "3"^^ . _:b213194382 . _:b213193635 . . _:b213193878 . _:b213193702 "3"^^ . _:b213194377 . _:b213193697 "3"^^ . _:b213194376 . _:b213194438 . _:b213193696 "3"^^ . _:b213194211 . _:b213193490 . _:b213193375 . _:b213194379 . _:b213193699 "3"^^ . _:b213194378 . _:b213193698 "3"^^ . _:b213194478 . _:b213194389 . _:b213194244 . _:b213194595 . _:b213193709 "3"^^ . _:b213194388 . _:b213193708 "3"^^ . . _:b213194391 . _:b213193711 "3"^^ . _:b213193493 . _:b213194390 . _:b213194298 . . _:b213193710 "3"^^ . . _:b213194292 . . . _:b213194521 . _:b213194385 . _:b213193705 "3"^^ . . . _:b213194384 . _:b213193704 "3"^^ . _:b213193362 . _:b213194387 . . _:b213193707 "3"^^ . _:b213194386 . _:b213193706 "3"^^ . _:b213194397 . _:b213193717 "3"^^ . . _:b213194396 . _:b213194140 . _:b213193716 "3"^^ . . _:b213193329 . _:b213194399 . . _:b213193719 "3"^^ . . . _:b213194398 . . _:b213193718 "3"^^ . _:b213193836 . _:b213193539 . _:b213194393 . _:b213193713 "3"^^ . . _:b213194392 . _:b213193712 "3"^^ . . . _:b213194395 . _:b213193815 . _:b213193715 "3"^^ . _:b213193590 . _:b213194394 . _:b213193714 "3"^^ . _:b213194256 . _:b213194405 . _:b213193725 "3"^^ . _:b213193414 . _:b213194119 . _:b213194404 . . _:b213193724 "3"^^ . _:b213194407 . _:b213193727 "3"^^ . . _:b213194406 . _:b213193726 "3"^^ . _:b213194401 . _:b213193721 "3"^^ . . _:b213194400 . _:b95119 . _:b213193720 "3"^^ . _:b213194403 . _:b213193723 "3"^^ . _:b213194402 . _:b213193722 "3"^^ . . _:b213194413 . _:b213194412 . . _:b213193359 . _:b213194415 . _:b95124 . _:b213194414 . _:b95125 . . _:b213194409 . _:b95126 . . _:b213194408 . _:b95127 . _:b213194411 . _:b95120 . . _:b213194410 . _:b95121 . _:b213193583 . . _:b213194421 . _:b95122 . _:b213194234 . _:b213194420 . _:b95123 . . _:b213193484 . _:b95132 . _:b213194423 . . _:b213194422 . _:b95133 . _:b213194600 . . _:b213194417 . _:b95134 . _:b213193959 . . _:b213194416 . _:b95135 . _:b213193436 . . . _:b213194419 . _:b95128 . _:b213194418 . _:b95129 . _:b213194429 . _:b95130 . . . _:b95131 . _:b213194428 . _:b213194431 . _:b95140 . _:b95180 "Though daughter chromatids (Sumner, 1991) are not resolved until late in prophase, daughter replicons are known to be resolved soon after replication is complete (Selig et al., >>1992<<; Kitsberg et al., 1993)." . _:b213194430 . _:b95141 . . _:b213194425 . _:b95142 . _:b213194424 . _:b95143 . . _:b213194427 . _:b95136 . . _:b213193368 . _:b213194078 . . _:b213194426 . _:b95137 . . _:b213194437 . _:b95138 . _:b213193889 . _:b95139 . _:b213194436 . _:b213194439 . _:b95148 . . . _:b95149 . _:b213194438 . _:b213194030 . . . _:b213194433 . _:b95150 . _:b213194115 . . . _:b95151 . _:b213194432 . _:b213194435 . _:b95144 . . _:b213194434 . _:b95145 . _:b213194445 . _:b95146 . _:b213193489 . . . . . _:b213194444 . _:b95147 . _:b213193872 . _:b95156 . _:b213194447 . _:b213194446 . _:b95157 . . _:b213194441 . _:b95158 . _:b213194440 . _:b95159 . _:b213194443 . _:b95152 . _:b213194442 . _:b95153 . _:b213194453 . _:b95154 . . _:b213194452 . _:b95155 . _:b213194455 . _:b95164 . . _:b95165 . _:b213194454 . _:b213194449 . _:b95166 . . _:b213194448 . _:b95167 . _:b213193779 . _:b213193708 . . _:b213194451 . _:b95160 . . _:b213194450 . _:b95161 . _:b213194461 . _:b95162 . _:b213194460 . _:b95163 . _:b213194463 . _:b95172 . . _:b95173 . _:b213194462 . _:b213194457 . _:b95174 . _:b213194261 . _:b95175 . _:b213194456 . _:b213193656 . . _:b213194459 . _:b95168 . _:b213194547 . _:b213194458 . _:b95169 . _:b213194252 . _:b213193555 . _:b95170 . _:b213194469 . _:b213194468 . _:b95171 . _:b213193828 . _:b213194471 . _:b95180 . _:b213194470 . _:b95181 . . _:b213194465 . _:b95182 . _:b213194464 . _:b95183 . _:b213194467 . _:b95176 . _:b213193839 . . _:b95177 . _:b213194466 . _:b213194448 . _:b213193377 . _:b213193491 . _:b95178 . _:b213194477 . . _:b213194127 . . _:b95179 . _:b213194476 . _:b213194479 . _:b95188 . . _:b213194478 . _:b95189 . _:b213194473 . _:b95190 . . _:b213194472 . _:b95191 . . _:b213194475 . _:b95184 . _:b213194389 . _:b213194474 . _:b95185 . _:b213194485 . _:b95186 . _:b213194503 . _:b213193531 . _:b213194377 . _:b95187 . _:b213194484 . . _:b213194487 . _:b95196 . . _:b95197 . _:b213194486 . _:b213194158 . _:b213194481 . _:b95198 . . _:b213194480 . . _:b213193727 . _:b95192 . _:b213194483 . . _:b213194482 . _:b95193 . _:b213194493 . _:b95194 . _:b213194492 . _:b95195 . _:b213194495 . _:b213194494 . . _:b213194489 . _:b213194471 . _:b213194488 . . _:b213194491 . . _:b213193417 . _:b213194490 . _:b213193989 . _:b95150 . _:b213193988 . . _:b213193466 . _:b213193991 . . _:b213193990 . . _:b213194174 . _:b213193985 . _:b213193984 . _:b213193987 . . . _:b213193986 . . _:b213193997 . _:b213193996 . . _:b213193999 . _:b213194202 . _:b213193987 . _:b213193998 . . _:b213194422 . _:b213194366 . _:b213193993 . . _:b213193992 . _:b213193558 . . _:b95179 . _:b213193995 . _:b213193392 . _:b213193438 . _:b213193994 . _:b213193954 . _:b213194005 . _:b213194004 . . _:b213194024 . _:b213194007 . . . _:b213194006 . _:b213194549 . . . _:b213194001 . . _:b213194000 . _:b213194430 . _:b213194537 . _:b213194003 . _:b213193703 . . _:b213193774 . _:b213194002 . _:b213194013 . . . _:b213194012 . _:b213193966 . _:b213194015 . _:b213194208 . _:b213194014 . . _:b213194009 . . _:b213194008 . _:b95152 "regions, corresponding to chromosomal R bands in mitosis, are labeled at the beginning of S phase and must complete synthesis before late synthesis in regions corresponding to mitotic G bands can proceed (for review see Drouin et al., >>1994<<). This distinction implies that elements of the mitotic organization must persist throughout interphase when each chromosome occupies a discrete \u201Cterritory\u201D (Cremer et al., 1993) that provides a reasonably stable environment for" . _:b213194259 . _:b213194011 . _:b213194010 . _:b213194021 . _:b95125 . . _:b213194020 . _:b213194604 . _:b213193775 . _:b213194023 . _:b213193789 . _:b213194563 . . _:b213194022 . _:b213194017 . _:b213193698 . _:b213194016 . . . _:b213194019 . _:b213194018 . _:b213194029 . _:b95185 "Simple calculations show that most replication foci must contain many replicons (Nakamura et al., >>1986<<). Throughout S phase, an average human chromosome of 145 Mbp has \u223C12 active sites; if each were a single replicon with forks growing at \u223C2 kbp/min S phase would take \u223C50 h." . _:b213194186 . _:b213194028 . . . _:b213194031 . . _:b213194030 . _:b213194025 . _:b213194094 . _:b213194024 . _:b213194027 . _:b213194026 . _:b213193594 . _:b213194037 . _:b213194036 . . . _:b213194039 . _:b213194038 . . . _:b213193363 . _:b213194472 . _:b213194033 . _:b213194032 . _:b213194035 . _:b213194034 . _:b213194045 . _:b213193547 . _:b213194044 . _:b213194047 . _:b95198 "As very similar numbers of synthetic sites are active at any time during the first 3 h of S phase, it is possible that once activated, each replication factory (Hoz\u00E1k et al., >>1993<<) recruits and replicates consecutive replicon clusters in turn." . _:b213194046 . _:b213193734 . _:b213194041 . _:b213194040 . _:b213193895 . _:b213194043 . _:b213193883 . _:b213194042 . . _:b213193795 . . _:b213194053 . _:b95155 . _:b213194291 . . _:b213194052 . _:b213194055 . _:b213193989 . _:b213194054 . . _:b213194049 . . _:b213193786 . _:b213194048 . _:b213193784 . _:b213194051 . _:b213194050 . . _:b213194062 . _:b213194061 . . _:b213194060 . _:b95175 "replication foci appear to survive mitosis and persist throughout the subsequent cell cycle, this approach provides an opportunity to analyze how certain aspects of nuclear structure and function might be linked (Sparvoli et al., >>1994<<; first observed by Meng, C., and R. Berezney. 1991. J. Cell Biol. 115:9a; as discussed in Jackson, 1995b and Berezney et al., 1995a )." . _:b213194135 . _:b213194063 . _:b213194062 . _:b213194056 . _:b213194057 . _:b213194056 . _:b213194580 . _:b213194059 . _:b213193332 . _:b213194058 . _:b213194022 . . _:b213194069 . _:b213194068 . . _:b213194071 . _:b213194070 . _:b213194283 . _:b213193442 . _:b213194065 . _:b213194064 . _:b213193347 . . _:b213193994 . . . _:b213194067 . _:b213193578 . _:b213194066 . . . . _:b213194077 . _:b213194076 . . _:b213194079 . _:b213194150 . _:b213194078 . _:b213194255 . _:b213193751 . _:b213194073 . _:b213193589 . _:b213194072 . _:b213194384 . _:b213194075 . _:b213194074 . . . _:b213194085 . _:b213194084 . _:b213194087 . _:b95148 . _:b213194086 . . _:b213194081 . _:b213194080 . . _:b213194083 . _:b213194082 . _:b213194093 . _:b95133 "However, labeling with BrdU in vivo allows the distribution of replicons labeled during any interval of S phase to be visualized in any subsequent cell cycle phase (Sparvoli et al., >>1994<<). DNA pulse labeled at the onset of S phase was shown to persist as labeled foci independently of DNA synthesis (Fig. 1, B\u2013D). In G2 phase, these cells had 1275 \u00B1 205 foci (n = 25). This 1.7-fold increase in the number of labeled foci" . _:b213194092 . _:b213194154 . . _:b213193337 . _:b213194095 . _:b213194094 . _:b213193567 . . _:b213194089 . . _:b213194088 . _:b213193374 . _:b213194091 . _:b213194345 . _:b213193799 . _:b213194051 . _:b213194090 . _:b213194101 . _:b95145 "and Stillman, 1996) that define sites where DNA synthesis initiates (Fangman and Brewer, 1992) and shown how these direct a single initiation event at the appropriate time of each cell cycle (Diffley and Cocker, 1992; Cocker et al., >>1996<<). In higher eukaryotes, with much more complex genomes, the elusive nature of replication origins (Coverley and Laskey, 1994) has prompted the suggestion that an efficient S phase will rely on \u201Cthe interplay between specific DNA" . _:b213194100 . _:b213194395 . _:b213194200 . _:b213194103 . _:b213194123 . _:b213194102 . _:b213194274 . _:b213193953 . _:b213194097 . . _:b213194096 . _:b213194099 . _:b213193324 . _:b213194098 . _:b213193354 . _:b213193582 . _:b213194109 . . _:b213194108 . _:b213194494 . _:b213194111 . _:b213194076 . . _:b213194110 . _:b213193647 . _:b213193697 . _:b213194282 . _:b213194500 . . _:b213194105 . _:b213193811 . . _:b213194104 . _:b213193600 . _:b213194107 . . . . _:b213193863 . _:b213194106 . _:b213194117 . _:b213194348 . _:b213194116 . _:b213194169 . . _:b213193901 . _:b213193678 . _:b213194064 . _:b213194119 . . _:b213194118 . _:b213193888 . . _:b213194113 . . _:b213194112 . _:b213193602 . . _:b213194115 . _:b213194114 . . _:b213194125 . . _:b213193776 . _:b213194124 . _:b213194127 . . _:b213194126 . _:b213193858 . . . _:b213194121 . _:b213194120 . _:b213194013 . _:b213193627 . _:b213193743 . _:b213194123 . . . _:b213194505 . _:b213194122 . _:b213194133 . _:b213194132 . _:b95174 . _:b213194135 . _:b213194134 . _:b213194129 . _:b213194128 . _:b213193346 . _:b95137 "2 F) of foci reflects the length of different human chromosomes (Morton, >>1991<<); with the obvious exception of the poorly labeled inactive X chromosome (Fig." . _:b213194131 . _:b213194130 . . . _:b213194141 . _:b213194140 . _:b213194143 . _:b213194240 . _:b213194142 . . . _:b213194137 . _:b213194136 . _:b213194139 . _:b213194138 . _:b213194149 . . _:b213194148 . _:b213194431 . _:b213194151 . . _:b213193702 . _:b213193977 . _:b213194150 . _:b213193443 . _:b213194145 . . _:b213194144 . _:b213194147 . _:b213194146 . _:b213194157 . _:b213194378 . _:b213194156 . _:b213193692 . _:b95152 . _:b213194159 . _:b213194158 . _:b213193887 . _:b213194153 . _:b213193974 . _:b213194152 . _:b213194155 . _:b213194154 . . _:b213194165 . _:b213193818 . . _:b213194164 . . _:b213194167 . _:b213194093 . _:b213194166 . _:b213194232 . _:b213194161 . . _:b213194160 . . _:b213194163 . _:b213193976 . _:b213194162 . . . _:b213194173 . _:b95172 "Once labeled, replication foci also present a useful tool for the analysis of genome organization (for review see Drouin et al., >>1994<<; Dolbeare, 1996)." . _:b213194172 . _:b213193812 . . . _:b213194175 . _:b213194174 . . _:b213194459 . . _:b213194169 . . _:b213194168 . _:b213193465 . _:b95172 . _:b213194171 . _:b213193444 . . _:b213194170 . . _:b213194045 . _:b213194181 . _:b213193980 . _:b213194180 . _:b213193333 . _:b213194346 . _:b213194183 . _:b213194254 . _:b213194182 . _:b213193642 . _:b213194177 . _:b95136 "1 D; Sparvoli et al., >>1994<<) suggest that different replicons of individual foci (see below) remain associated throughout the cell cycle, surviving structural changes that accompany mitosis." . _:b213194176 . _:b213193626 . _:b213194179 . _:b213194217 . _:b213194190 . _:b213194178 . _:b213194450 . _:b213194601 . . _:b213194189 . _:b213194460 . . . _:b213194188 . _:b213194372 . . _:b213194191 . _:b213194190 . _:b213194023 . _:b213193624 . _:b213194185 . _:b213194184 . . . _:b213194187 . . _:b213194264 . _:b213193808 . _:b213194186 . _:b213194197 . _:b213194196 . _:b213194199 . _:b213194198 . . _:b213194558 . _:b213193485 . _:b213194193 . . _:b213194192 . _:b213193674 . _:b213194195 . _:b213193837 . _:b213194194 . _:b213194205 . . _:b213193793 . _:b213194204 . . _:b213194207 . _:b213193785 . _:b213194206 . _:b213194182 . _:b213194201 . _:b213194200 . _:b213194203 . _:b213194015 . _:b213194202 . _:b213194213 . _:b213194212 . _:b213194215 . . . _:b213194214 . _:b213193973 . . _:b95176 . _:b213193990 . _:b213194209 . _:b213193720 . _:b213193401 . _:b213194208 . _:b213193803 . _:b213193772 . _:b213194211 . _:b213193881 . _:b213193921 . _:b213194525 . _:b213194335 . _:b213194210 . . _:b213194221 . _:b213194035 . _:b213194220 . . . _:b213194223 . . _:b213194222 . _:b213193755 . _:b213194217 . _:b213194453 . _:b213194216 . _:b213194219 . _:b213194218 . _:b213194229 . _:b213194228 . _:b213194231 . _:b213194354 . _:b213194230 . _:b213193870 . . _:b213194225 . _:b95173 . _:b213194224 . . _:b213194206 . . _:b213194227 . . . . . _:b213194226 . _:b213194237 . _:b213194236 . _:b213194351 . _:b213194081 . _:b213194239 . _:b213194238 . _:b213194233 . _:b213194232 . _:b213194235 . . _:b213194234 . . _:b213193733 . . _:b213193732 . _:b213193735 . _:b95189 "Indeed, it may seem remarkable that two sequences separated by 1-Mbp DNA should be \u223C1.5-\u03BCm apart in nuclei (van den Engh et al., >>1992<<; Yokota et al., 1995) when the same sequences folded as a 10-nm chromatin fiber might be separated by as much as \u223C55 \u03BCm (this extent of separation is clearly not possible in a typical human nucleus)." . _:b213193734 . _:b213194122 . _:b213193729 . _:b213193728 . _:b213193731 . . _:b213193730 . . _:b213193741 . _:b213193701 . _:b213193740 . _:b213193743 . . _:b213194605 . . _:b213193742 . _:b213193842 . _:b213194362 . _:b95123 "To estimate the extension of DNA fibers, spreads were prepared from HeLa cells infected with adenovirus serotype 2 and grown in medium supplemented with 100 \u03BCM BrdU 15\u201320 h after infection (Pombo et al., >>1994<<). Abundant Br-labeled DNA molecules measured 13.9 \u00B1 1.3 \u03BCm (mean \u00B1 SD; n = 50). As the viral genome is 36 kbp, the extension of these DNA fibers is 2.59 \u00B1 0.24 kbp/\u03BCm." . _:b213193737 . . _:b213193419 . _:b213193736 . . _:b213193739 . _:b213193738 . . _:b213193749 . _:b213193748 . _:b213193751 . _:b213193404 . _:b213194479 . _:b213193750 . _:b213193745 . . . . _:b213193744 . _:b213193747 . _:b95163 . . _:b213193420 . _:b213193746 . . _:b213193757 . _:b213193756 . _:b213193759 . _:b213193758 . _:b213193753 . _:b213193752 . . . _:b213193755 . _:b213193754 . _:b213193765 . _:b213193671 . _:b213193764 . . _:b95189 . _:b213193767 . _:b213194279 . _:b213193766 . _:b95157 "Detailed analyses of different mammalian cells suggests that most relicons are 50\u2013300 kbp (for review see Edenberg and Huberman, 1975; Hand, >>1978<<). This range was calculated from the length of labeled DNA fibers assuming that B form DNA in solution spreads so that 3-kbp DNA measures 1 \u03BCm. Indeed, whereas DNA fibers spread as described here can stretch to as much as twice their" . _:b213193944 . . _:b213193761 . _:b213193760 . . . _:b213194368 . . . _:b213194260 . _:b213193763 . . _:b213193762 . _:b213193884 . _:b213194141 . _:b213193773 . _:b213193677 . . _:b213194548 . _:b213193772 . _:b213193746 . . _:b213194235 . _:b213193775 . _:b213193955 . . _:b213193774 . _:b213193352 . . _:b213193769 . _:b213193724 . _:b213194286 . _:b213193768 . _:b213193771 . _:b213193770 . _:b213193781 . _:b213193780 . _:b213193415 . _:b213193449 . _:b213193783 . _:b213193380 . _:b213193782 . _:b213194210 . _:b213193777 . _:b213193776 . _:b213193779 . . _:b213193778 . _:b213193789 . _:b95129 . _:b213193421 . _:b213193788 . _:b213193791 . _:b213194118 . _:b213193790 . _:b213193785 . _:b213193784 . _:b213193787 . _:b213193685 . _:b213193786 . _:b213193797 . _:b213193796 . _:b213193799 . _:b213194488 . _:b213193798 . _:b213193393 . . _:b213193504 . _:b213193793 . . _:b213193792 . _:b213193795 . _:b213194257 . _:b213193794 . _:b213193805 . _:b213193804 . _:b213193807 . _:b213194396 . _:b213193806 . _:b213193384 . _:b213194027 . _:b213193801 . _:b213193800 . _:b213193803 . _:b213193802 . _:b213193813 . _:b213193812 . . _:b213193815 . . _:b213193814 . _:b213193905 . . _:b213193809 . _:b213193808 . _:b213193591 . _:b213194066 . _:b213193811 . _:b213193810 . . _:b213193821 . _:b213193820 . _:b213194380 . _:b213193823 . _:b213193822 . _:b213193446 . _:b95131 "HeLa cells synchronized at the S phase border using aphidicolin (Jackson, 1995a ) incorporated BrdU into 749 \u00B1 154 (n = 50) replication foci." . _:b213193817 . . . _:b213193816 . _:b213194468 . _:b213193819 . _:b95143 . _:b213193818 . _:b213193829 . . _:b213193828 . . _:b213193831 . _:b213193830 . . _:b213193825 . _:b213194317 . _:b213193824 . _:b213194313 . _:b213193827 . _:b213193847 . . _:b213193562 . _:b213193826 . _:b213194512 . _:b213194152 . _:b213194406 . _:b213194147 . _:b213193837 . _:b213193710 . _:b213193542 . _:b213193836 . _:b95145 . _:b213193434 . _:b213193830 . _:b213193839 . _:b213193351 . _:b213193838 . . _:b213193833 . _:b213194470 . _:b213193832 . . . _:b213193875 . _:b213193835 . . _:b213193834 . _:b213193845 . _:b213193844 . _:b213193847 . _:b213193846 . _:b213193841 . . _:b213193840 . _:b213193336 . _:b213193541 . _:b213193843 . _:b213193842 . _:b213193853 . . _:b213193852 . _:b213193855 . . _:b213193854 . _:b213193849 . _:b213193339 . _:b213193848 . _:b213193926 . . _:b213193851 . _:b213193919 . . _:b213193850 . _:b213194087 . _:b213193861 . _:b213193519 . _:b213193860 . . _:b213193863 . _:b95138 "Different replication forks elongate at similar rates after cell synchronization (Jackson, 1995a ). It is likely, therefore, that sites with the range of intensities seen above (e.g., Fig." . _:b213193862 . _:b213193857 . _:b213193856 . _:b213193859 . _:b213193858 . _:b213193622 . _:b213193869 . _:b213194323 . _:b213193868 . _:b213193871 . _:b213193870 . _:b213193807 . _:b213193865 . _:b213193864 . .