title: Rif1 prevents resection of DNA breaks and promotes immunoglobulin class switching.
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.
authors.affiliation: Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USA.
authors.forename: Michela
authors.initials: M
authors.lastname: Di Virgilio
authors.forename: Elsa
authors.initials: E
authors.lastname: Callen
authors.forename: Arito
authors.initials: A
authors.lastname: Yamane
authors.forename: Wenzhu
authors.initials: W
authors.lastname: Zhang
authors.forename: Mila
authors.initials: M
authors.lastname: Jankovic
authors.forename: Alexander D
authors.initials: AD
authors.lastname: Gitlin
authors.forename: Niklas
authors.initials: N
authors.lastname: Feldhahn
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Resch
authors.forename: Thiago Y
authors.initials: TY
authors.lastname: Oliveira
authors.forename: Brian T
authors.initials: BT
authors.lastname: Chait
authors.forename: André
authors.initials: A
authors.lastname: Nussenzweig
authors.forename: Rafael
authors.initials: R
authors.lastname: Casellas
authors.forename: Davide F
authors.initials: DF
authors.lastname: Robbiani
authors.forename: Michel C
authors.initials: MC
authors.lastname: Nussenzweig
mesh_terms: D000818:Animals; D064007:Ataxia Telangiectasia Mutated Proteins; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D002478:Cells, Cultured; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism*; D004247:DNA / Q000378:metabolism*; D053903:DNA Breaks, Double-Stranded; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D016193:G1 Phase; D016195:G2 Phase; D042822:Genomic Instability; D017578:Immunoglobulin Class Switching; D051379:Mice; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D016196:S Phase; D034501:Telomere-Binding Proteins / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D000071857:Tumor Suppressor p53-Binding Protein 1
chemical_list: D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; C492748:Rif1 protein, mouse; D034501:Telomere-Binding Proteins; C498302:Trp53bp1 protein, mouse; D025521:Tumor Suppressor Proteins; D000071857:Tumor Suppressor p53-Binding Protein 1; D004247:DNA; D064007:Ataxia Telangiectasia Mutated Proteins; C576325:Atm protein, mouse; D017346:Protein Serine-Threonine Kinases