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Systematic proximal mapping of the classical RAD51 paralogs unravel functionally and clinically relevant interactors for genome stability.
Simo Cheyou, Estelle; Boni, Jacopo; Boulais, Jonathan; Pinedo-Carpio, Edgar; Malina, Abba; Sherill-Rofe, Dana; Luo, Vincent M; Goncalves, Christophe; Bagci, Halil; Maters, Alexandra; Cuella-Martin, Raquel; Tabach, Yuval; Del Rincon, Sonia; Côté, Jean-Francois; Rivera, Barbara; Orthwein, Alexandre.
Afiliação
  • Simo Cheyou E; Lady Davis Institute for Medical Research, Segal Cancer Centre, Jewish General Hospital, Montreal, Canada.
  • Boni J; Gerald Bronfman Department of Oncology, McGill University, Montreal, Canada.
  • Boulais J; Bellvitge Biomedical Research Institute, IDIBELL, Barcelona, Spain.
  • Pinedo-Carpio E; Institut de Recherches Cliniques de Montréal (IRCM), Montreal, Canada.
  • Malina A; Lady Davis Institute for Medical Research, Segal Cancer Centre, Jewish General Hospital, Montreal, Canada.
  • Sherill-Rofe D; Division of Experimental Medicine, McGill University, Montreal, Canada.
  • Luo VM; Lady Davis Institute for Medical Research, Segal Cancer Centre, Jewish General Hospital, Montreal, Canada.
  • Goncalves C; Gerald Bronfman Department of Oncology, McGill University, Montreal, Canada.
  • Bagci H; Department of Developmental Biology and Cancer Research, Institute for Medical Research-Israel-Canada, Hebrew University of Jerusalem, Jerusalem, Israel.
  • Maters A; Lady Davis Institute for Medical Research, Segal Cancer Centre, Jewish General Hospital, Montreal, Canada.
  • Cuella-Martin R; Department of Microbiology and Immunology, McGill University, Montreal, Canada.
  • Tabach Y; Lady Davis Institute for Medical Research, Segal Cancer Centre, Jewish General Hospital, Montreal, Canada.
  • Del Rincon S; Gerald Bronfman Department of Oncology, McGill University, Montreal, Canada.
  • Côté JF; Institut de Recherches Cliniques de Montréal (IRCM), Montreal, Canada.
  • Rivera B; Department of Anatomy and Cell Biology, McGill University, Montreal, Canada.
  • Orthwein A; Lady Davis Institute for Medical Research, Segal Cancer Centre, Jewish General Hospital, Montreal, Canada.
PLoS Genet ; 18(11): e1010495, 2022 11.
Article em En | MEDLINE | ID: mdl-36374936
Homologous recombination (HR) plays an essential role in the maintenance of genome stability by promoting the repair of cytotoxic DNA double strand breaks (DSBs). More recently, the HR pathway has emerged as a core component of the response to replication stress, in part by protecting stalled replication forks from nucleolytic degradation. In that regard, the mammalian RAD51 paralogs (RAD51B, RAD51C, RAD51D, XRCC2, and XRCC3) have been involved in both HR-mediated DNA repair and collapsed replication fork resolution. Still, it remains largely obscure how they participate in both processes, thereby maintaining genome stability and preventing cancer development. To gain better insight into their contribution in cellulo, we mapped the proximal interactome of the classical RAD51 paralogs using the BioID approach. Aside from identifying the well-established BCDX2 and CX3 sub-complexes, the spliceosome machinery emerged as an integral component of our proximal mapping, suggesting a crosstalk between this pathway and the RAD51 paralogs. Furthermore, we noticed that factors involved RNA metabolic pathways are significantly modulated within the BioID of the classical RAD51 paralogs upon exposure to hydroxyurea (HU), pointing towards a direct contribution of RNA processing during replication stress. Importantly, several members of these pathways have prognostic potential in breast cancer (BC), where their RNA expression correlates with poorer patient outcome. Collectively, this study uncovers novel functionally relevant partners of the different RAD51 paralogs in the maintenance of genome stability that could be used as biomarkers for the prognosis of BC.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Instabilidade Genômica / Rad51 Recombinase Tipo de estudo: Prognostic_studies Limite: Animals / Humans Idioma: En Ano de publicação: 2022 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Instabilidade Genômica / Rad51 Recombinase Tipo de estudo: Prognostic_studies Limite: Animals / Humans Idioma: En Ano de publicação: 2022 Tipo de documento: Article