The function of RAD52 N-terminal domain is essential for viability of BRCA-deficient cells.
Nucleic Acids Res
; 48(22): 12778-12791, 2020 12 16.
Article
em En
| MEDLINE
| ID: mdl-33275133
ABSTRACT
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias da Mama
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Rad51 Recombinase
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Proteína Rad52 de Recombinação e Reparo de DNA
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Reparo de DNA por Recombinação
Limite:
Female
/
Humans
Idioma:
En
Revista:
Nucleic Acids Res
Ano de publicação:
2020
Tipo de documento:
Article