Nature：DNA复制新机制

生物通报道，来自法国巴黎居里研究院（Institut Curie）Michelle Debatisse教授带领的研究小组发现哺乳动物细胞DNA复制的新机制。研究发现，DNA复制过程中并非只存在一个单一的复制起点，还存在休眠的复制起点，一旦一个复制起点出现问题，休眠的启动就能被激活促进DNA继续复制。并且复制叉和染色质环间的关系对DNA复制有重要的影响。

 

在细胞复制有丝分裂过程分为三个重要的阶段，分别是G1、S和G2三个时期。S期又叫DNA合成期，该时期细胞不仅完成DNA复制，同时进行合成组蛋白和非组蛋白。新复制的DNA与新合成的组蛋白迅速结合构成核小体，由核小体串连成染色质细丝，从而完成染色质复制。S期的持续时间约6小时。

 

在基因组复制的过程里，需要在一个复制起点启动DNA复制程序，一般而言，在S期，基因组只需要从一个固定的启动点开始复制行为。单一的复制起点机制是为了防止新的复制起点出现，阻碍正常DNA复制，多个启动会导致DNA复制不完全，复制紊乱。不过，在DNA复制期间，这一机制如何在空间上控制DNA复制起点的详细理论还没被科学家发现。

 

为了研究这一机制，居里研究所的Debatisse教授以中国仓鼠细胞系为研究模型，细胞在复制的S期依靠复制叉（replication forks）和染色质环（hromatin loops）来调控基因组复复制活动。研究发现，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。更深入的研究发现，位于染色质环向核基质附着的附着点附近的复制，在下一个细胞S期中会被优先激发。

 

原文摘要：Replication fork movement sets chromatin loop size and origin choice in mammalian cells

 

【Abstract】

Genome stability requires one, and only one, DNA duplication at each S phase. The mechanisms preventing origin firing on newly replicated DNA are well documented, 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.

 

（生物通 张欢）