The canine RAD51 mutation leads to the attenuation of interaction with PALB2

被引:4
|
作者
Uemura, Mitsuki [1 ]
Ochiai, Kazuhiko [1 ]
Morimatsu, Masami [2 ]
Michishita, Masaki [3 ]
Onozawa, Eri [1 ]
Azakami, Daigo [4 ]
Uno, Yumiko [1 ]
Yoshikawa, Yasunaga [5 ]
Sasaki, Takanori [6 ]
Watanabe, Masami [6 ]
Omi, Toshinori [1 ]
机构
[1] Nippon Vet & Life Sci Univ, Fac Vet Sci, Sch Vet Nursing & Technol, Tokyo, Japan
[2] Hokkaido Univ, Grad Sch Vet Med, Dept Dis Control, Lab Lab Anim Sci & Med, Sapporo, Hokkaido 0600818, Japan
[3] Nippon Vet & Life Sci Univ, Fac Vet Sci, Dept Vet Pathol, Tokyo, Japan
[4] Tokyo Univ Agr & Technol, Fac Agr, Lab Vet Clin Oncol, Tokyo, Japan
[5] Kitasato Univ, Sch Vet Med, Lab Vet Biochem, Aomori, Japan
[6] Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Urol, Okayama, Japan
关键词
BRCA2; cancer-associated single nucleotide polymorphisms (SNPs); DNA double-strand breaks (DSB); homologous recombination (HR); mammary gland tumour; HOMOLOGOUS RECOMBINATION; BRCA2; EXPRESSION; RESIDUE; DNA;
D O I
10.1111/vco.12542
中图分类号
S85 [动物医学(兽医学)];
学科分类号
0906 ;
摘要
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.
引用
收藏
页码:247 / 255
页数:9
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