title: The human SRCAP chromatin remodeling complex promotes DNA-end resection.
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.
authors.affiliation: Life Sciences Institute, Zhejiang University, Hangzhou, Zhejiang 310058, China.
authors.forename: Shunli
authors.initials: S
authors.lastname: Dong
authors.affiliation: Life Sciences Institute, Zhejiang University, Hangzhou, Zhejiang 310058, China.
authors.forename: Jinhua
authors.initials: J
authors.lastname: Han
authors.affiliation: Life Sciences Institute, Zhejiang University, Hangzhou, Zhejiang 310058, China.
authors.forename: Hongxia
authors.initials: H
authors.lastname: Chen
authors.affiliation: Life Sciences Institute, Zhejiang University, Hangzhou, Zhejiang 310058, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Liu
authors.affiliation: Department of Anatomy & Center for Cancer Research, University of Hong Kong, Hong Kong, China.
authors.forename: Michael S Y
authors.initials: MSY
authors.lastname: Huen
authors.affiliation: Laboratory of Cancer Genomics and Individualized Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Yeran
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Laboratory of Cancer Genomics and Individualized Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Caixia
authors.initials: C
authors.lastname: Guo
authors.affiliation: Life Sciences Institute, Zhejiang University, Hangzhou, Zhejiang 310058, China. Electronic address: jhuang@zju.edu.cn.
authors.forename: Jun
authors.initials: J
authors.lastname: Huang
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics / Q000378:metabolism; D000251:Adenosine Triphosphatases / Q000235:genetics* / Q000378:metabolism; D002843:Chromatin / Q000235:genetics* / Q000378:metabolism; D042002:Chromatin Assembly and Disassembly; D019465:Craniofacial Abnormalities / Q000235:genetics / Q000378:metabolism; D053903:DNA Breaks, Double-Stranded; D004249:DNA Damage; D005455:Fluorescent Antibody Technique; D006130:Growth Disorders / Q000235:genetics / Q000378:metabolism; D006367:HeLa Cells; D006345:Heart Septal Defects, Ventricular / Q000235:genetics / Q000378:metabolism; D059765:Homologous Recombination; D006801:Humans; D016133:Polymerase Chain Reaction
chemical_list: D002843:Chromatin; D000251:Adenosine Triphosphatases; C119652:SRCAP protein, human