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Rif1 prevents resection of DNA breaks and promotes immunoglobulin class switching

Item Type:Article
Title:Rif1 prevents resection of DNA breaks and promotes immunoglobulin class switching
Creators Name:Di Virgilio, M. and Callen, E. and Yamane, A. and Zhang, W. and Jankovic, M. and Gitlin, A.D. and Feldhahn, N. and Resch, W. and Oliveira, T.Y. and Chait, B.T. and Nussenzweig, A. and Casellas, R. and Robbiani, D.F. and Nussenzweig, M.C.
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.
Keywords:Ataxia Telangiectasia Mutated Proteins, B-Lymphocytes, Cell Cycle Proteins, Cultured Cells, DNA, DNA Repair, DNA-Binding Proteins, Double-Stranded DNA Breaks, G1 Phase, G2 Phase, Genomic Instability, Immunoglobulin Class Switching, Non-Histone Chromosomal Proteins, Phosphorylation, Protein-Serine-Threonine Kinases, S Phase, Telomere-Binding Proteins, Tumor Suppressor Proteins, Animals, Mice
Source:Science
ISSN:0036-8075
Publisher:American Association for the Advancement of Science (U.S.A.)
Volume:339
Number:6120
Page Range:711-715
Date:8 February 2013
Official Publication:https://doi.org/10.1126/science.1230624
PubMed:View item in PubMed

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