Expression of human BRCA2 in Saccharomyces cerevisiae complements the loss of RAD52 in double-strand break repair.
BRCA2
Double-strand break
Homologous recombination repair
Ionizing radiation
Rad52
Saccharomyces cerevisiae
Journal
Current genetics
ISSN: 1432-0983
Titre abrégé: Curr Genet
Pays: United States
ID NLM: 8004904
Informations de publication
Date de publication:
Dec 2023
Dec 2023
Historique:
received:
09
10
2023
accepted:
31
10
2023
revised:
30
10
2023
pubmed:
7
11
2023
medline:
7
11
2023
entrez:
7
11
2023
Statut:
ppublish
Résumé
BRCA2 is a tumor-suppressor gene that is normally expressed in the breast and ovarian tissue of mammals. The BRCA2 protein mediates the repair of double-strand breaks (DSBs) using homologous recombination, which is a conserved pathway in eukaryotes. Women who express missense mutations in the BRCA2 gene are predisposed to an elevated lifetime risk for both breast cancer and ovarian cancer. In the present study, the efficiency of human BRCA2 (hBRCA2) in DSB repair was investigated in the budding yeast Saccharomyces cerevisiae. While budding yeast does not possess a true BRCA2 homolog, they have a potential functional homolog known as Rad52, which is an essential repair protein involved in mediating homologous recombination using the same mechanism as BRCA2 in humans. Therefore, to examine the functional overlap between Rad52 in yeast and hBRCA2, we expressed the wild-type hBRCA2 gene in budding yeast with or without Rad52 and monitored ionizing radiation resistance and DSB repair efficiency. We found that the expression of hBRCA2 in rad52 mutants increases both radiation resistance and DSB repair frequency compared to cells not expressing BRCA2. Specifically, BRCA2 improved the protection against ionizing radiation by at least 1.93-fold and the repair frequency by 6.1-fold. In addition, our results show that homology length influences repair efficiency in rad52 mutant cells, which impacts BRCA2 mediated repair of DSBs. This study provides evidence that S. cerevisiae could be used to monitor BRCA2 function, which can help in understanding the genetic consequences of BRCA2 variants and how they may contribute to cancer progression.
Identifiants
pubmed: 37934232
doi: 10.1007/s00294-023-01278-y
pii: 10.1007/s00294-023-01278-y
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
301-308Informations de copyright
© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.
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