The Human SRCAP Chromatin Remodeling Complex Promotes DNA-End Resection
The Human SRCAP Chromatin Remodeling Complex Promotes DNA-End Resection
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人类 SRCAP 染色质重塑复合物促进 DNA 末端切除
DOI：
10.1016/j.cub.2014.07.081
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发表时间：
2014-09-22
期刊：
影响因子：
9.2
通讯作者：
Huang, Jun
中科院分区：
文献类型：
--
作者：
Dong, Shunli;Han, Jinhua;Huang, Jun
背景：通过同源重组修复DNA双链断裂（DSB）需要切除DSB末端的5 '-3'。在脊椎动物中，DSB切除由CtIP和MRE 11-RAD 50-NBS 1（MRN）复合物的协同作用启动。然而，这个过程是如何发生的背景下，染色质仍然没有很好地understood.Results：在这里，我们确定了人类SRCAP染色质重塑复合物作为一个因素，促进CtIP依赖的DNA末端切除。我们表明，SRCAP，这是突变的浮港综合征，赋予抵抗DNA损伤诱导剂，并招募到DSB。此外，我们证明，SRCAP是需要DNA末端切除，从而为招聘RPA和RAD 51 DSBs，并为随后的同源重组。最后，我们发现，SRCAP形成一个复杂的CtIP和促进积累的CUP在DSB通过一个机制，涉及其ATP酶activity.Conclusions：我们的研究涉及人类SRCAP染色质重塑复合物作为一种新的调节DNA损伤反应，编排适当的信号和修复DSB的背景下，染色质。
Background: Repair of DNA double-strand breaks (DSBs) by homologous recombination requires 5'-3' resection of the DSB ends. In vertebrates, DSB resection is initiated by the collaborative action of CtIP and the MRE11-RAD50-NBS1 (MRN) complex. However, how this process occurs within the context of chromatin is still not well understood.Results: Here we identify the human SRCAP chromatin remodeling complex as a factor that promotes CtIP-dependent DNA-end resection. We show that SRCAP, which is mutated in Floating-Harbor syndrome, confers resistance to DNA damage-inducing agents and is recruited to DSBs. Moreover, we demonstrate that SRCAP is required for DNA-end resection, and thereby for recruitment of RPA and RAD51 to DSBs, and for the ensuing homologous recombination. Finally, we reveal that SRCAP forms a complex with CtIP and promotes accumulation of CUP at DSBs through a mechanism involving its ATPase activity.Conclusions: Our study implicates the human SRCAP chromatin remodeling complex as a novel regulator of DNA damage responses that orchestrates proper signaling and repair of DSBs in the context of chromatin.