TY - JOUR
T1 - Systematic proximal mapping of the classical RAD51 paralogs unravel functionally and clinically relevant interactors for genome stability
AU - Cheyou, Estelle Simo
AU - Boni, Jacopo
AU - Boulais, Jonathan
AU - Pinedo-Carpio, Edgar
AU - Malina, Abba
AU - Sherill-Rofe, Dana
AU - Luo, Vincent M.
AU - Goncalves, Christophe
AU - Bagci, Halil
AU - Maters, Alexandra
AU - Cuella-Martin, Raquel
AU - Tabach, Yuval
AU - del Rincon, Sonia
AU - Côté, Jean Francois
AU - Rivera, Barbara
AU - Orthwein, Alexandre
N1 - Publisher Copyright: Copyright: © 2022 Simo Cheyou et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
PY - 2022/11/14
Y1 - 2022/11/14
N2 - 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 subcomplexes, 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.
AB - 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 subcomplexes, 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.
UR - http://www.scopus.com/inward/record.url?scp=85143150764&partnerID=8YFLogxK
U2 - https://doi.org/10.1371/journal.pgen.1010495
DO - https://doi.org/10.1371/journal.pgen.1010495
M3 - مقالة
C2 - 36374936
SN - 1553-7390
VL - 18
JO - PLoS Genetics
JF - PLoS Genetics
IS - 11
M1 - e1010495
ER -