Human CtIP promotes DNA end resection.
Human CtIP promotes DNA end resection.
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DOI：
10.1038/nature06337
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发表时间：
2007-11-22
期刊：
影响因子：
64.8
通讯作者：
Jackson, Stephen P
中科院分区：
文献类型：
--
作者：
Sartori, Alessandro A;Lukas, Claudia;Coates, Julia;Mistrik, Martin;Fu, Shuang;Bartek, Jiri;Baer, Richard;Lukas, Jiri;Jackson, Stephen P
在细胞周期的S期和G2期，DNA双链断裂（DSB）被加工成单链DNA，触发atr依赖性检查点信号和DSB通过同源重组（HR）修复。先前的研究表明MRE11复合体与DSB处理事件有关。在这里，我们发现人CtIP蛋白对dsb诱导剂具有抗性，并且仅在S/G2中被dsb招募。此外，我们发现CtIP是DSB切除所必需的，因此也是RPA和ATR在DSB上的招募和随后的ATR激活所必需的。此外，我们确定CtIP在物理和功能上与MRE11复合物相互作用，并且CtIP和MRE11都是高效HR所必需的。最后，我们发现CtIP与Sae2序列同源，Sae2参与酵母中依赖mre11的DSB加工。这些发现确定了ctip样蛋白在控制DSB切除、检查点信号传导和HR中的进化保守作用。
In the S and G2 phases of the cell cycle, DNA double-strand breaks (DSBs) are processed into single-stranded DNA, triggering ATR-dependent checkpoint signaling and DSB repair by homologous recombination (HR). Previous work has implicated the MRE11 complex in such DSB processing events. Here, we show that the human CtIP protein confers resistance to DSB-inducing agents and is recruited to DSBs exclusively in S/G2. Moreover, we reveal that CtIP is required for DSB resection, and thereby for recruitment of RPA and ATR to DSBs and ensuing ATR activation. Furthermore, we establish that CtIP physically and functionally interacts with the MRE11 complex, and that both CtIP and MRE11 are required for efficient HR. Finally, we reveal that CtIP displays sequence homology with Sae2, which is involved in MRE11-dependent DSB processing in yeast. These findings establish evolutionarily conserved roles for CtIP-like proteins in controlling DSB resection, checkpoint signaling and HR.