title: Polymorphisms of canine BRCA2 BRC repeats affecting interaction with RAD51.
abstract: Mutations in the breast cancer susceptibility gene BRCA2 leading to the failure of interactions with the recombinase RAD51 are associated with an increased risk of cancer in humans. This interaction depends on the eight BRC repeat (BRC1-8) sequences in BRCA2. We previously reported that canine BRC3 has two polymorphisms (T1425P and K1435R) influencing the interaction with RAD51, and 1435R was identified in mammary tumor dog samples. In this study, we investigated the sequence variations of BRC3 and 4 in 236 dogs of five breeds. Allele frequencies of 1425P and 1435R were 0.063 and 0.314, respectively, and there was no other polymorphism in the sequenced region. A mammalian two-hybrid assay using BRC3-4 sequences demonstrated that 1425P allele reduced the binding strength with RAD51 but 1435R had no effect. These results may provide an insight into the functions of not only individual but also multiple BRC repeats of BRCA2 in dogs.
authors: Department of Veterinary Nursing and Technology, School of Veterinary Science, Nippon Veterinary and Life Science University.
authors: Kazuhiko
authors: K
authors: Ochiai
authors: Toshina
authors: T
authors: Ishiguro-Oonuma
authors: Yasunaga
authors: Y
authors: Yoshikawa
authors: Chihiro
authors: C
authors: Udagawa
authors: Yuiko
authors: Y
authors: Kato
authors: Masami
authors: M
authors: Watanabe
authors: Makoto
authors: M
authors: Bonkobara
authors: Masami
authors: M
authors: Morimatsu
authors: Toshinori
authors: T
authors: Omi
mesh_terms: D000818:Animals; D024682:BRCA2 Protein / Q000235:genetics* / Q000378:metabolism; D004285:Dogs; D005787:Gene Frequency; D024522:Genes, BRCA2; D056726:Genetic Association Studies; D057809:HEK293 Cells; D006801:Humans; D011110:Polymorphism, Genetic; D011485:Protein Binding; D051135:Rad51 Recombinase / Q000378:metabolism*
chemical_list: D024682:BRCA2 Protein; D051135:Rad51 Recombinase