在哺乳動(dòng)物細(xì)胞中,,基因組每個(gè)細(xì)胞周期經(jīng)歷一輪復(fù)制。復(fù)制的很多起點(diǎn)從未被激發(fā),,但它們是隨時(shí)準(zhǔn)備被激發(fā)的——如果基因組的一部分有不能被復(fù)制的危險(xiǎn)時(shí),,比如說(shuō)如果一個(gè)復(fù)制叉(replication fork)的進(jìn)展停滯時(shí)。
Courbet等人發(fā)現(xiàn),,如果復(fù)制叉進(jìn)展減慢時(shí),,休眠的起點(diǎn)是可以被激發(fā)的,而且這將影響染色質(zhì)環(huán)(chromatin loop)的大小,。另外,,位于染色質(zhì)環(huán)向核基質(zhì)附著的附著點(diǎn)附近的起點(diǎn),在下一個(gè)細(xì)胞周期中會(huì)被優(yōu)先激發(fā),。(生物谷Bioon.com)
生物谷推薦原始出處:
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.
(責(zé)任編輯:chenguang)