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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, N.I.H., Intramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Ataxia Telangiectasia Mutated Proteins
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B-Lymphocytes / immunology
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B-Lymphocytes / metabolism
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Cell Cycle Proteins / antagonists & inhibitors
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Cell Cycle Proteins / metabolism
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Cells, Cultured
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Chromosomal Proteins, Non-Histone / metabolism*
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DNA / metabolism*
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DNA Breaks, Double-Stranded*
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DNA Repair
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DNA-Binding Proteins / antagonists & inhibitors
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DNA-Binding Proteins / metabolism*
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G1 Phase
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G2 Phase
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Genomic Instability
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Immunoglobulin Class Switching*
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Mice
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Phosphorylation
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Protein Serine-Threonine Kinases / antagonists & inhibitors
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Protein Serine-Threonine Kinases / metabolism
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S Phase
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Telomere-Binding Proteins / metabolism*
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Tumor Suppressor Proteins / antagonists & inhibitors
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Tumor Suppressor Proteins / metabolism
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Tumor Suppressor p53-Binding Protein 1
Substances
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Cell Cycle Proteins
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Chromosomal Proteins, Non-Histone
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DNA-Binding Proteins
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Rif1 protein, mouse
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Telomere-Binding Proteins
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Trp53bp1 protein, mouse
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Tumor Suppressor Proteins
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Tumor Suppressor p53-Binding Protein 1
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DNA
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Ataxia Telangiectasia Mutated Proteins
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Atm protein, mouse
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Protein Serine-Threonine Kinases