期刊
CURRENT BIOLOGY
卷 24, 期 18, 页码 2097-2110出版社
CELL PRESS
DOI: 10.1016/j.cub.2014.07.081
关键词
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资金
- National Basic Research Program of China [2012CB944402, 2013CB911003]
- National Program for Special Support of Eminent Professionals
- National Natural Science Funds for Distinguished Young Scholars
- National Natural Science Foundation of China [31071243, 31171347, 31090360]
- Zhejiang University K.P. Chao's High Technology Development Foundation
- China's Fundamental Research Funds for the Central Universities
- Ministry of Science and Technology [2012CB966600, 2013CB945303]
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.
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