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SHLD 2/ FAM 35A co‐operates with REV 7 to coordinate DNA double‐strand break repair pathway choice
Author(s) -
Findlay Steven,
Heath John,
Luo Vincent M,
Malina Abba,
Morin Théo,
Coulombe Yan,
Djerir Billel,
Li Zhigang,
Samiei Arash,
SimoCheyou Estelle,
Karam Martin,
Bagci Halil,
Rahat Dolev,
Grapton Damien,
Lavoie Elise G,
Dove Christian,
Khaled Husam,
Kuasne Hellen,
Mann Koren K,
Klein Kathleen Oros,
Greenwood Celia M,
Tabach Yuval,
Park Morag,
Côté JeanFrancois,
Masson JeanYves,
Maréchal Alexandre,
Orthwein Alexandre
Publication year - 2018
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.15252/embj.2018100158
Subject(s) - biology
DNA double‐strand breaks ( DSB s) 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 53 BP 1, in complex with its effectors RIF 1 and REV 7, and BRCA 1. However, it remains unknown how the 53 BP 1/ RIF 1/ REV 7 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 REV 7 interactors and elucidate the role of SHLD 2 (previously annotated as FAM 35A and RINN 2) as an effector of REV 7 in the NHEJ pathway. FAM 35A depletion impairs NHEJ ‐mediated DNA repair and compromises antibody diversification by class switch recombination ( CSR ) in B cells. FAM 35A accumulates at DSB s in a 53 BP 1‐, RIF 1‐, and REV 7‐dependent manner and antagonizes HR by limiting DNA end resection. In fact, FAM 35A is part of a larger complex composed of REV 7 and SHLD 1 (previously annotated as C20orf196 and RINN 3), which promotes NHEJ and limits HR . Together, these results establish SHLD 2 as a novel effector of REV 7 in controlling the decision‐making process during DSB repair.