RAD51 paralog function in replicative DNA damage and tolerance

Rein, Hayley L, Bernstein, Kara A and Baldock, Robbie ORCID: 0000-0002-4649-2966 (2021) RAD51 paralog function in replicative DNA damage and tolerance. Current Opinion in Genetics and Development, 71. pp. 86-91. doi:10.1016/j.gde.2021.06.010

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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.

Item Type:	Article
Article Type:	Article
Additional Information:	Special Issue
Subjects:	Q Science > Q Science (General) Q Science > QH Natural history > QH426 Genetics
Divisions:	Schools and Research Institutes > School of Education and Science
Research Priority Areas:	Place, Environment and Community
Depositing User:	Robbie Baldock
Date Deposited:	10 Aug 2021 13:30
Last Modified:	31 Aug 2023 08:57
URI:	https://eprints.glos.ac.uk/id/eprint/10049

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