RAD51 paralogs regulate double strand break repair pathway choice by limiting Ku complex retention

Abstract

RAD51 paralogs are a group of conserved proteins in eukaryotes that are involved in the repair of DNA breaks at several levels. On one hand, they help the strand invasion step catalyzed by RAD51. Also, they play late roles in Holliday Junction metabolism. Here we uncover a new role of the RAD51 paralogs at an earlier event in the repair of broken chromosomes. All five RAD51 paralogs affect the balance between double strand break repair pathways. Specifically, they favor homology-mediated repair over non-homologous end-joining. Such role is independent of RAD51 or the checkpoint activity of these proteins. Moreover, it defines a novel control point of double strand break repair independent and subsequent to DNA-end resection initiation.\n\nMechanistically, RAD51 paralogs limit the retention of Ku80 at the sites of DNA breaks. Thus, our data extend the role of this family of proteins to the earliest event of double strand break repair.