TY - JOUR
T1 - Polymorphisms of canine BRCA2 BRC repeats affecting interaction with RAD51
AU - Ochiai, Kazuhiko
AU - Ishiguro-Oonuma, Toshina
AU - Yoshikawa, Yasunaga
AU - Udagawa, Chihiro
AU - Kato, Yuiko
AU - Watanabe, Masami
AU - Bonkobara, Makoto
AU - Morimatsu, Masami
AU - Omi, Toshinori
N1 - Publisher Copyright:
© 2015 Biomedical Research Foundation. All rights reserved.
PY - 2015
Y1 - 2015
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84927763869&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84927763869&partnerID=8YFLogxK
U2 - 10.2220/biomedres.36.155
DO - 10.2220/biomedres.36.155
M3 - Article
C2 - 25876666
AN - SCOPUS:84927763869
SN - 0388-6107
VL - 36
SP - 155
EP - 158
JO - Biomedical Research
JF - Biomedical Research
IS - 2
ER -
