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Curr Biol. 2014 Sep 22;24(18):2097-2110. doi: 10.1016/j.cub.2014.07.081. Epub 2014 Aug 28.

The human SRCAP chromatin remodeling complex promotes DNA-end resection.

Author information

1
Life Sciences Institute, Zhejiang University, Hangzhou, Zhejiang 310058, China.
2
Department of Anatomy & Center for Cancer Research, University of Hong Kong, Hong Kong, China.
3
Laboratory of Cancer Genomics and Individualized Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China.
4
Life Sciences Institute, Zhejiang University, Hangzhou, Zhejiang 310058, China. Electronic address: jhuang@zju.edu.cn.

Abstract

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 CtIP 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.

PMID:
25176633
DOI:
10.1016/j.cub.2014.07.081
[Indexed for MEDLINE]
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