https://ror.org/0112mx960 Institute of Innovative Research, Tokyo Institute of Technology, Yokohama, Japan.
https://ror.org/0112mx960 Institute of Innovative Research, Tokyo Institute of Technology, Yokohama, Japan
Life Sci Alliance. 2023 Nov 28;7(2). doi: 10.26508/lsa.202302342. Print 2024 Feb.
The 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, BRCA2 homologs are found in many Basidiomycota species but not in Ascomycota species. BRCA2 (Brh2, for CA2 omolog) 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 mutant, and the double mutant. Brh2 is likely the BRCA2 ortholog that functions as an indispensable auxiliary factor for Rad51.
肿瘤抑制因子在同源重组中起着关键作用，通过调节 RAD51（真核同源重组酶）来实现。我们在一种担子菌酵母中鉴定出 BRCA2 同源物，该同源物存在于许多担子菌物种中，但不存在于子囊菌物种中。BRCA2（Brh2，CA2 同源物）大约是人类 BRCA2 的三分之一大小。Brh2 带有三个潜在的 BRC 重复序列和两个寡核苷酸/寡糖结合域。还鉴定出 DSS1 的同源物，DSS1 是一种作为 BRCA2 必需伴侣的小酸性蛋白。酵母双杂交实验表明 Brh2 与 Rad51 和 Dss1 相互作用。与人类 BRCA2 不同，Brh2 不是正常细胞生长所必需的，而 Dss1 的缺失会导致生长缓慢。Brh2 的缺失导致对 UV 和电离辐射的敏感性显著增加，并且其 HR 能力（如通过基因靶向效率测定）受损。这些表型与 突变体和 双突变体的表型无法区分。Brh2 可能是 BRCA2 的同源物，作为 Rad51 不可或缺的辅助因子发挥作用。
