Postreplicative recruitment of cohesin to double-strand breaks is required for DNA repair

被引:424
作者
Ström, L
Lindroos, HB
Shirahige, K
Sjögren, C
机构
[1] Karolinska Inst, Dept Cell & Mol Biol, S-17177 Stockholm, Sweden
[2] Tokyo Inst Technol, Ctr Gene Res, Midori Ku, Yokohama, Kanagawa 2268501, Japan
基金
日本学术振兴会;
关键词
D O I
10.1016/j.molcel.2004.11.026
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Chromosome stability depends on accurate chromosome segregation and efficient DNA double-strand break (DSB) repair. Sister chromatid cohesion, established during S phase by the protein complex cohesin, is central to both processes. In the absence of cohesion, chromosomes missegregate and G2-phase DSB repair fails. Here, we demonstrate that G2-phase repair also requires the presence of cohesin at the damage site. Cohesin components are shown to be recruited to extended chromosome regions surrounding DNA breaks induced during G2. We find that in the absence of functional cohesin-loading proteins (Scc2/Scc4), the accumulation of cohesin at DSBs is abolished and repair is defective, even though sister chromatids are connected by S phase generated cohesion. Evidence is also provided that DSB induction elicits establishment of sister chromatid cohesion in G2, implicating that damage-recruited cohesin facilitates DNA repair by tethering chromatids.
引用
收藏
页码:1003 / 1015
页数:13
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