Skip Navigation

Publication Detail

Title: RAD51 paralog function in replicative DNA damage and tolerance.

Authors: Rein, Hayley L; Bernstein, Kara A; Baldock, Robert A

Published In Curr Opin Genet Dev, (2021 Dec)

Abstract: RAD51 paralog gene mutations are observed in both hereditary breast and ovarian cancers. Classically, defects in RAD51 paralog function are associated with homologous recombination (HR) deficiency and increased genomic instability. Several recent investigative advances have enabled characterization of non-canonical RAD51 paralog function during DNA replication. Here we discuss the role of the RAD51 paralogs and their associated complexes in integrating a robust response to DNA replication stress. We highlight recent discoveries suggesting that the RAD51 paralogs complexes mediate lesion-specific tolerance of replicative stress following exposure to alkylating agents and the requirement for the Shu complex in fork restart upon fork stalling by dNTP depletion. In addition, we describe the role of the BCDX2 complex in restraining and promoting fork remodeling in response to fluctuating dNTP pools. Finally, we highlight recent work demonstrating a requirement for RAD51C in recognizing and tolerating methyl-adducts. In each scenario, RAD51 paralog complexes play a central role in lesion recognition and bypass in a replicative context. Future studies will determine how these critical functions for RAD51 paralog complexes contribute to tumorigenesis.

PubMed ID: 34311385 Exiting the NIEHS site

MeSH Terms: DNA; DNA Damage/genetics; DNA Repair*/genetics; DNA Replication/genetics; Rad51 Recombinase*/genetics; Rad51 Recombinase*/metabolism

Back
to Top