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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., Callen, E., Yamane, A., Zhang, W., Jankovic, M., Gitlin, A.D., Feldhahn, N., Resch, W., Oliveira, T.Y., Chait, B.T., Nussenzweig, A., Casellas, R., 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
Publisher:American Association for the Advancement of Science
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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