RT Journal Article
SR Electronic
T1 RAD51 promotes non-homologous genetic rearrangements that are prevented by 53BP1
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 768788
DO 10.1101/768788
A1 Josée Guirouilh-Barbat
A1 Wei Yu
A1 Loelia Babin
A1 Elisa Yaniz Galende
A1 Tatiana Popova
A1 Ayeong So
A1 Chloé Lescale
A1 Marc-Henri Stern
A1 Erika Brunet
A1 Ludovic Deriano
A1 Bernard S. Lopez
YR 2019
UL http://biorxiv.org/content/early/2019/09/14/768788.abstract
AB Homologous recombination (HR), which requires long sequence homologies, is considered a high fidelity mechanism, preserving genome stability. In contrast, we show here that the central HR players RAD51 or BRCA2, promote genetic instability, fostering translocations and capture of ectopic chromosomal sequences when joining distant DNA breaks. Surprisingly, these events do not involve sequence homologies. Moreover, our data reveal that 53BP1 protects against RAD51-mediated non-homologous genetic rearrangements. Finally, analysis of a large panel of breast tumors revealed that BRCA2 proficiency is associated with increased frequency of capture of non-homologous sequences at junctions of structural variants (translocations, duplications, inversions, deletions). These data reveal that HR proteins (RAD51, BRCA2) possess the intrinsic capacity to generate genetic instability through sequence homology-independent processes, and that 53BP1 protects against it. We propose that BRCA2/RAD51-mediated genome instability occurs in the course of sequence homology search for HR.