SHLD2/FAM35A co-operates with REV7 to coordinate DNA double-strand break repair pathway choice.

Autor: Findlay S; Lady Davis Institute for Medical Research, Segal Cancer Centre, Jewish General Hospital, Montreal, QC, Canada.; Division of Experimental Medicine, McGill University, Montreal, QC, Canada., Heath J; Lady Davis Institute for Medical Research, Segal Cancer Centre, Jewish General Hospital, Montreal, QC, Canada.; Division of Experimental Medicine, McGill University, Montreal, QC, Canada., Luo VM; Lady Davis Institute for Medical Research, Segal Cancer Centre, Jewish General Hospital, Montreal, QC, Canada.; Department of Microbiology and Immunology, McGill University, Montreal, QC, Canada., Malina A; Lady Davis Institute for Medical Research, Segal Cancer Centre, Jewish General Hospital, Montreal, QC, Canada.; Gerald Bronfman Department of Oncology, McGill University, Montreal, QC, Canada., Morin T; Department of Biology, Université de Sherbrooke, Sherbrooke, QC, Canada., Coulombe Y; Genome Stability Laboratory, CHU de Québec Research Center, Quebec City, QC, Canada.; Department of Molecular Biology, Medical Biochemistry and Pathology, Laval University Cancer Research Center, Quebec City, QC, Canada., Djerir B; Department of Biology, Université de Sherbrooke, Sherbrooke, QC, Canada., Li Z; Lady Davis Institute for Medical Research, Segal Cancer Centre, Jewish General Hospital, Montreal, QC, Canada., Samiei A; Lady Davis Institute for Medical Research, Segal Cancer Centre, Jewish General Hospital, Montreal, QC, Canada.; Division of Experimental Medicine, McGill University, Montreal, QC, Canada., Simo-Cheyou E; Lady Davis Institute for Medical Research, Segal Cancer Centre, Jewish General Hospital, Montreal, QC, Canada.; Gerald Bronfman Department of Oncology, McGill University, Montreal, QC, Canada., Karam M; Division of Experimental Medicine, McGill University, Montreal, QC, Canada., Bagci H; Institut de Recherches Cliniques de Montréal (IRCM), Montreal, QC, Canada.; Department of Anatomy and Cell Biology, McGill University, Montreal, QC, Canada., Rahat D; Department of Developmental Biology and Cancer Research, The Institute for Medical Research Israel-Canada, The Hebrew University of Jerusalem, Jerusalem, Israel., Grapton D; Lady Davis Institute for Medical Research, Segal Cancer Centre, Jewish General Hospital, Montreal, QC, Canada., Lavoie EG; Lady Davis Institute for Medical Research, Segal Cancer Centre, Jewish General Hospital, Montreal, QC, Canada., Dove C; Lady Davis Institute for Medical Research, Segal Cancer Centre, Jewish General Hospital, Montreal, QC, Canada.; Division of Experimental Medicine, McGill University, Montreal, QC, Canada., Khaled H; Lady Davis Institute for Medical Research, Segal Cancer Centre, Jewish General Hospital, Montreal, QC, Canada.; Division of Experimental Medicine, McGill University, Montreal, QC, Canada., Kuasne H; Rosalind and Morris Goodman Cancer Research Centre, McGill University, Montreal, QC, Canada., Mann KK; Lady Davis Institute for Medical Research, Segal Cancer Centre, Jewish General Hospital, Montreal, QC, Canada.; Division of Experimental Medicine, McGill University, Montreal, QC, Canada.; Gerald Bronfman Department of Oncology, McGill University, Montreal, QC, Canada., Klein KO; Lady Davis Institute for Medical Research, Segal Cancer Centre, Jewish General Hospital, Montreal, QC, Canada., Greenwood CM; Lady Davis Institute for Medical Research, Segal Cancer Centre, Jewish General Hospital, Montreal, QC, Canada.; Department of Epidemiology, Biostatistics and Occupational Health, MGill University, Montreal, QC, Canada., Tabach Y; Department of Developmental Biology and Cancer Research, The Institute for Medical Research Israel-Canada, The Hebrew University of Jerusalem, Jerusalem, Israel., Park M; Rosalind and Morris Goodman Cancer Research Centre, McGill University, Montreal, QC, Canada., Côté JF; Institut de Recherches Cliniques de Montréal (IRCM), Montreal, QC, Canada.; Department of Anatomy and Cell Biology, McGill University, Montreal, QC, Canada.; Département de Biochimie et Médecine Moléculaire, Université de Montréal, Montreal, QC, Canada.; Département de Médecine (Programmes de Biologie Moléculaire), Université de Montréal, Montreal, QC, Canada., Masson JY; Genome Stability Laboratory, CHU de Québec Research Center, Quebec City, QC, Canada.; Department of Molecular Biology, Medical Biochemistry and Pathology, Laval University Cancer Research Center, Quebec City, QC, Canada., Maréchal A; Department of Biology, Université de Sherbrooke, Sherbrooke, QC, Canada., Orthwein A; Lady Davis Institute for Medical Research, Segal Cancer Centre, Jewish General Hospital, Montreal, QC, Canada alexandre.orthwein@mcgill.ca.; Division of Experimental Medicine, McGill University, Montreal, QC, Canada.; Department of Microbiology and Immunology, McGill University, Montreal, QC, Canada.; Gerald Bronfman Department of Oncology, McGill University, Montreal, QC, Canada.
Jazyk: angličtina
Zdroj: The EMBO journal [EMBO J] 2018 Sep 14; Vol. 37 (18). Date of Electronic Publication: 2018 Aug 28.
DOI: 10.15252/embj.2018100158
Abstrakt: DNA double-strand breaks (DSBs) can be repaired by two major pathways: non-homologous end-joining (NHEJ) and homologous recombination (HR). DNA repair pathway choice is governed by the opposing activities of 53BP1, in complex with its effectors RIF1 and REV7, and BRCA1. However, it remains unknown how the 53BP1/RIF1/REV7 complex stimulates NHEJ and restricts HR to the S/G2 phases of the cell cycle. Using a mass spectrometry (MS)-based approach, we identify 11 high-confidence REV7 interactors and elucidate the role of SHLD2 (previously annotated as FAM35A and RINN2) as an effector of REV7 in the NHEJ pathway. FAM35A depletion impairs NHEJ-mediated DNA repair and compromises antibody diversification by class switch recombination (CSR) in B cells. FAM35A accumulates at DSBs in a 53BP1-, RIF1-, and REV7-dependent manner and antagonizes HR by limiting DNA end resection. In fact, FAM35A is part of a larger complex composed of REV7 and SHLD1 (previously annotated as C20orf196 and RINN3), which promotes NHEJ and limits HR Together, these results establish SHLD2 as a novel effector of REV7 in controlling the decision-making process during DSB repair.
(© 2018 The Authors. Published under the terms of the CC BY 4.0 license.)
Databáze: MEDLINE
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