Systematic proximal mapping of the classical RAD51 paralogs unravel functionally and clinically relevant interactors for genome stability

Estelle Simo Cheyou, Jacopo Boni, Jonathan Boulais, Edgar Pinedo-Carpio, Abba Malina, Dana Sherill-Rofe, Vincent M. Luo, Christophe Goncalves, Halil Bagci, Alexandra Maters, Raquel Cuella-Martin, Yuval Tabach, Sonia del Rincon, Jean Francois Côté, Barbara Rivera*, Alexandre Orthwein*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


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.

Original languageAmerican English
Article numbere1010495
JournalPLoS Genetics
Issue number11
StatePublished - 14 Nov 2022

Bibliographical note

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.


Dive into the research topics of 'Systematic proximal mapping of the classical RAD51 paralogs unravel functionally and clinically relevant interactors for genome stability'. Together they form a unique fingerprint.

Cite this