2. Academic Validation
  3. ATM and CDK2 control chromatin remodeler CSB to inhibit RIF1 in DSB repair pathway choice

ATM and CDK2 control chromatin remodeler CSB to inhibit RIF1 in DSB repair pathway choice

  • Nat Commun. 2017 Dec 4;8(1):1921. doi: 10.1038/s41467-017-02114-x.
Nicole L Batenburg 1,  John R Walker 1,  Sylvie M Noordermeer 2 3,  Nathalie Moatti 2,  Daniel Durocher 2,  Xu-Dong Zhu 4
Affiliations

Affiliations

  • 1 Department of Biology, McMaster University, Hamilton, Ontario, L8S 4K1, Canada.
  • 2 Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, 600 University Avenue, Toronto, Ontario, M5G 1X5, Canada.
  • 3 Department of Human Genetics, Leiden University Medical Centre, Einthovenweg 20, 2333 ZC, Leiden, The Netherlands.
  • 4 Department of Biology, McMaster University, Hamilton, Ontario, L8S 4K1, Canada. [email protected].
PMID: 29203878 DOI: 10.1038/s41467-017-02114-x
Abstract

CSB, a member of the SWI2/SNF2 superfamily, is implicated in DNA double-strand break (DSB) repair. However, how it regulates this repair process is poorly understood. Here we uncover that CSB interacts via its newly identified winged helix domain with RIF1, an effector of 53BP1, and that this interaction mediates CSB recruitment to DSBs in S phase. At DSBs, CSB remodels chromatin by evicting histones, which limits RIF1 and its effector MAD2L2 but promotes BRCA1 accumulation. The chromatin remodeling activity of CSB requires not only damage-induced phosphorylation on S10 by ATM but also cell cycle-dependent phosphorylation on S158 by cyclin A-CDK2. Both modifications modulate the interaction of the CSB N-terminal region with its ATPase domain, the activity of which has been previously reported to be autorepressed by the N-terminal region. These results suggest that ATM and CDK2 control the chromatin remodeling activity of CSB in the regulation of DSB repair pathway choice.

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