Postreplicative recruitment of cohesin to double-strand breaks is required for DNA repair
Postreplicative recruitment of cohesin to double-strand breaks is required for DNA repair
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DOI：
10.1016/j.molcel.2004.11.026
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发表时间：
2004-12-22
期刊：
影响因子：
16
通讯作者：
Sjögren, C
中科院分区：
文献类型：
--
作者：
Ström, L;Lindroos, HB;Sjögren, C
染色体的稳定性取决于准确的染色体分离和有效的DNA双链断裂(DSB)修复。姐妹染色单体凝聚力是在S阶段由蛋白质复合体粘附素建立的，是这两个过程的中心。在缺乏凝聚力的情况下，染色体错误分离，G2期DSB修复失败。在这里，我们证明了G2期修复也需要损伤部位存在粘附素。研究表明，粘附素成分被招募到G2期间诱导的DNA断裂周围的延伸染色体区域。我们发现，在缺乏功能性粘附素加载蛋白(Scc2/Scc4)的情况下，即使姐妹染色单体通过S时相产生的凝聚力连接在一起，DSB上粘附素的积累也被取消，修复功能受损。也有证据表明，DSB诱导诱导G2中姐妹染色单体凝聚力的建立，暗示损伤招募的粘附素通过拴系染色单体促进DNA修复。
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.