Current Biology. 2014 Sep 22;24(18):2097-110.

Shunli Dong, Jinhua Han, Hongxia Chen, Ting Liu,Michael S.Y. Huen, Yeran Yang, Caixia Guo,and Jun Huang*

Summary

Background: Repair of DNA double-strand breaks (DSBs) by homologous recombination requires 50-30 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.

Text link: http://www.sciencedirect.com/science/article/pii/S0960982214009828#