School of Veterinary Nursing and Technology, Faculty of Veterinary Science, Nippon Veterinary and Life Science University, Tokyo, Japan.
Laboratory of Laboratory Animal Science and Medicine, Department of Disease Control, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Japan.
Vet Comp Oncol. 2020 Jun;18(2):247-255. doi: 10.1111/vco.12542. Epub 2019 Sep 13.
RAD51 forms a complex with BRCA2 and plays a central role in the DNA damage response pathway that is associated with homologous recombination. The structures of RAD51 and its homologues are highly conserved from prokaryotes to higher eukaryotes. Although a large number of BRCA2 mutations have been reported, there are only a few reports on the mutations of RAD51, which have been shown in humans and dogs. However, several mutations of canine RAD51 were identified from mammary gland tumour tissues in a recent study. Some of these mutations seem to have an influence on the homo-oligomerization or interaction with "Partner and localizer of BRCA2" (PALB2). In this study, we cloned the canine PALB2 homologue and investigated the effect on its interaction with the RAD51 mutants to evaluate the alteration in the function of RAD51 mutants. The A209S and T225S mutants of RAD51 show an attenuation of the interaction between RAD51 and PALB2. These results indicate that the canine RAD51 mutations can potentially alter the homologous recombination pathways in response to DNA damage in dogs.
RAD51 与 BRCA2 形成复合物,在与同源重组相关的 DNA 损伤反应途径中发挥核心作用。RAD51 及其同源物的结构在从原核生物到高等真核生物中高度保守。尽管已经报道了大量的 BRCA2 突变,但只有少数关于 RAD51 突变的报道,这些突变在人类和狗中都有发现。然而,在最近的一项研究中,从乳腺肿瘤组织中鉴定出了几种犬 RAD51 的突变。其中一些突变似乎对同源寡聚化或与“BRCA2 伙伴和定位器”(PALB2)的相互作用有影响。在这项研究中,我们克隆了犬 PALB2 同源物,并研究了其对 RAD51 突变体相互作用的影响,以评估 RAD51 突变体功能的改变。RAD51 的 A209S 和 T225S 突变体显示 RAD51 与 PALB2 之间相互作用的减弱。这些结果表明,犬 RAD51 突变可能会改变狗对 DNA 损伤的同源重组途径。