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Rif1 prevents resection of DNA breaks and promotes immunoglobulin class switching

Authors

  • M. Di Virgilio
  • E. Callen
  • A. Yamane
  • W. Zhang
  • M. Jankovic
  • A.D. Gitlin
  • N. Feldhahn
  • W. Resch
  • T.Y. Oliveira
  • B.T. Chait
  • A. Nussenzweig
  • R. Casellas
  • D.F. Robbiani
  • M.C. Nussenzweig

Journal

  • Science

Citation

  • Science 339 (6120): 711-715

Abstract

  • DNA double-strand breaks (DSBs) represent a threat to the genome because they can lead to the loss of genetic information and chromosome rearrangements. The DNA repair protein p53 binding protein 1 (53BP1) protects the genome by limiting nucleolytic processing of DSBs by a mechanism that requires its phosphorylation, but whether 53BP1 does so directly is not known. Here, we identify Rap1-interacting factor 1 (Rif1) as an ATM (ataxia-telangiectasia mutated) phosphorylation-dependent interactor of 53BP1 and show that absence of Rif1 results in 5'-3' DNA-end resection in mice. Consistent with enhanced DNA resection, Rif1 deficiency impairs DNA repair in the G(1) and S phases of the cell cycle, interferes with class switch recombination in B lymphocytes, and leads to accumulation of chromosome DSBs.


DOI

doi:10.1126/science.1230624