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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."xsd:string
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http://purl.uniprot.org/citations/25176633http://purl.uniprot.org/core/author"Chen H."xsd:string
http://purl.uniprot.org/citations/25176633http://purl.uniprot.org/core/author"Han J."xsd:string
http://purl.uniprot.org/citations/25176633http://purl.uniprot.org/core/author"Huang J."xsd:string
http://purl.uniprot.org/citations/25176633http://purl.uniprot.org/core/author"Liu T."xsd:string
http://purl.uniprot.org/citations/25176633http://purl.uniprot.org/core/author"Dong S."xsd:string
http://purl.uniprot.org/citations/25176633http://purl.uniprot.org/core/author"Guo C."xsd:string
http://purl.uniprot.org/citations/25176633http://purl.uniprot.org/core/author"Yang Y."xsd:string
http://purl.uniprot.org/citations/25176633http://purl.uniprot.org/core/author"Huen M.S.Y."xsd:string
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http://purl.uniprot.org/citations/25176633http://purl.uniprot.org/core/pages"2097-2110"xsd:string
http://purl.uniprot.org/citations/25176633http://purl.uniprot.org/core/title"The human SRCAP chromatin remodeling complex promotes DNA-end resection."xsd:string
http://purl.uniprot.org/citations/25176633http://purl.uniprot.org/core/volume"24"xsd:string
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