Analysis of the indispensable RAD51 cofactor BRCA2 in Naganishia liquefaciens, a Basidiomycota yeast

Life Sci Alliance. 2023 Nov 28;7(2):e202302342. doi: 10.26508/lsa.202302342. Print 2024 Feb.

Abstract

The BRCA2 tumor suppressor plays a critical role in homologous recombination by regulating RAD51, the eukaryotic homologous recombinase. We identified the BRCA2 homolog in a Basidiomycota yeast, Naganishia liquefaciens BRCA2 homologs are found in many Basidiomycota species but not in Ascomycota species. Naganishia BRCA2 (Brh2, for BRCA2 homolog) is about one-third the size of human BRCA2. Brh2 carries three potential BRC repeats with two oligonucleotide/oligosaccharide-binding domains. The homolog of DSS1, a small acidic protein serving as an essential partner of BRCA2 was also identified. The yeast two-hybrid assay shows the interaction of Brh2 with both Rad51 and Dss1. Unlike human BRCA2, Brh2 is not required for normal cell growth, whereas loss of Dss1 results in slow growth. The loss of Brh2 caused pronounced sensitivity to UV and ionizing radiation, and their HR ability, as assayed by gene-targeting efficiency, is compromised. These phenotypes are indistinguishable from those of the rad51 mutant, and the rad51 brh2 double mutant. Naganishia Brh2 is likely the BRCA2 ortholog that functions as an indispensable auxiliary factor for Rad51.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • BRCA2 Protein / genetics
  • Basidiomycota* / genetics
  • Basidiomycota* / metabolism
  • DNA Repair
  • DNA-Binding Proteins / metabolism
  • Fungal Proteins / metabolism
  • Humans
  • Rad51 Recombinase / genetics
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae Proteins* / metabolism
  • Ustilago* / genetics
  • Ustilago* / metabolism

Substances

  • DNA-Binding Proteins
  • Rad51 Recombinase
  • Fungal Proteins
  • RAD51 protein, human
  • BRCA2 protein, human
  • BRCA2 Protein
  • RAD51 protein, S cerevisiae
  • Saccharomyces cerevisiae Proteins

Supplementary concepts

  • Naganishia liquefaciens