在哺乳动物细胞中,基因组每个细胞周期经历一轮复制。复制的很多起点从未被激发,但它们是随时准备被激发的——如果基因组的一部分有不能被复制的危险时,比如说如果一个复制叉(replication fork)的进展停滞时。
Courbet等人发现,如果复制叉进展减慢时,休眠的起点是可以被激发的,而且这将影响染色质环(chromatin loop)的大小。另外,位于染色质环向核基质附着的附着点附近的起点,在下一个细胞周期中会被优先激发。(生物谷Bioon.com)
生物谷推荐原始出处:
Nature 455, 557-560 (25 September 2008) | doi:10.1038/nature07233
Replication fork movement sets chromatin loop size and origin choice in mammalian cells
Sylvain Courbet1, Sophie Gay1,2, Nausica Arnoult1,2, Gerd Wronka1, Mauro Anglana1, Olivier Brison1 & Michelle Debatisse1
1 Institut Curie, 26 rue d'Ulm, 75248 Paris, France; UPMC Univ. Paris 06, F-75005 Paris, France; CNRS UMR 7147
2 These authors contributed equally to this work.
Genome stability requires one, and only one, DNA duplication at each S phase. The mechanisms preventing origin firing on newly replicated DNA are well documented1, but much less is known about the mechanisms controlling the spacing of initiation events2,3, namely the completion of DNA replication. Here we show that origin use in Chinese hamster cells depends on both the movement of the replication forks and the organization of chromatin loops. We found that slowing the replication speed triggers the recruitment of latent origins within minutes, allowing the completion of S phase in a timely fashion. When slowly replicating cells are shifted to conditions of fast fork progression, although the decrease in the overall number of active origins occurs within 2 h, the cells still have to go through a complete cell cycle before the efficiency specific to each origin is restored. We observed a strict correlation between replication speed during a given S phase and the size of chromatin loops in the next G1 phase. Furthermore, we found that origins located at or near sites of anchorage of chromatin loops in G1 are activated preferentially in the following S phase. These data suggest a mechanism of origin programming in which replication speed determines the spacing of anchorage regions of chromatin loops, that, in turn, controls the choice of initiation sites.
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