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The function of RAD52 N-terminal domain is essential for viability of BRCA-deficient cells
Journal article   Open access   Peer reviewed

The function of RAD52 N-terminal domain is essential for viability of BRCA-deficient cells

Kritika Hanamshet and Alexander V Mazin
Nucleic acids research, v 48(22), pp 12778-12791
16 Dec 2020
DOI: https://doi.org/10.1093/nar/gkaa1145
PMID: 33275133
Featured in Collection :   UN Sustainable Development Goals @ Drexel
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https://doi.org/10.1093/nar/gkaa1145View
Published, Version of Record (VoR)CC BY V4.0,  Open

Abstract

BRCA1 Protein - genetics BRCA2 Protein - genetics Breast Neoplasms - genetics Breast Neoplasms - pathology Cell Line, Tumor DNA Damage - genetics DNA, Single-Stranded - genetics Female Gene Expression Regulation, Neoplastic - genetics Gene Knockout Techniques Humans Mutation - genetics Protein Binding - genetics Rad51 Recombinase - genetics Rad52 DNA Repair and Recombination Protein - genetics Recombinational DNA Repair - genetics
RAD52 is a member of the homologous recombination pathway that is important for survival of BRCA-deficient cells. Inhibition of RAD52 leads to lethality in BRCA-deficient cells. However, the exact mechanism of how RAD52 contributes to viability of BRCA-deficient cells remains unknown. Two major activities of RAD52 were previously identified: DNA or RNA pairing, which includes DNA/RNA annealing and strand exchange, and mediator, which is to assist RAD51 loading on RPA-covered ssDNA. Here, we report that the N-terminal domain (NTD) of RAD52 devoid of the potential mediator function is essential for maintaining viability of BRCA-deficient cells owing to its ability to promote DNA/RNA pairing. We show that RAD52 NTD forms nuclear foci upon DNA damage in BRCA-deficient human cells and promotes DNA double-strand break repair through two pathways: homology-directed repair (HDR) and single-strand annealing (SSA). Furthermore, we show that mutations in the RAD52 NTD that disrupt these activities fail to maintain viability of BRCA-deficient cells.

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17 citations in Web of Science
14 citations in Scopus

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Web of Science research areas
Biochemistry & Molecular Biology
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