著者
Yasunaga YOSHIKAWA Masami MORIMATSU Kazuhiko OCHIAI Toshina ISHIGURO-OONUMA Ryo MORIOKA Kento OKUDA Koichi ORINO
出版者
JAPANESE SOCIETY OF VETERINARY SCIENCE
雑誌
Journal of Veterinary Medical Science (ISSN:09167250)
巻号頁・発行日
pp.21-0006, (Released:2021-03-16)

Mammary tumors are the most common tumors in women and non-spayed female dogs. One of the reasons for mammary tumors is mutations of the tumor suppressor gene, BRCA2. BRCA2 participates in homologous recombination repair by interacting with the RAD51 recombinase. BRCA2 has two RAD51-binding domains, consisting of BRC repeats and the C-terminal RAD51-binding domain, respectively. Although several studies have addressed the function of the C-terminal RAD51-binding domain of human BRCA2, the amino acid sequences required for the RAD51-interaction activity remain unclear. In this study, the C-terminal RAD51-binding domains of canine and human BRCA2 were compared; the canine domain displayed a weaker interaction with RAD51. This difference was attributed to the C-terminal portion of the domain via a comparison between canine and human domains. Furthermore, peptides shorter than those previously reported displayed RAD51-interacting activity, and a core motif of this domain consisting of 25 amino acids was identified. Since a mutation (S3323N) was reported in the core motif of this domain, the effect of this mutation was evaluated. The mutant exhibited similar RAD51-binding activity as that of the wild-type protein, suggesting that the mutation was functionally neutral. These data suggested that the C-terminal portion of the BRCA2 C-terminal RAD51-binding domain influenced its RAD51-interaction activity, and a minimum core motif of 25 amino acids was identified in this domain. These data may help clarify BRCA2 function, as well as the tumorigenic effects of BRCA2 mutation.

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Identification of the core motif of the BRCA2 C-terminal RAD51-binding domain by comparing canine and human BRCA2. https://t.co/oRTmPGJfh5
Identification of the core motif of the BRCA2 C-terminal RAD51-binding domain by comparing canine and human BRCA2. https://t.co/oRTmPGrEpx
identification of the core motif of the BRCA2 C-terminal RAD51-binding domain by comparing canine and human BRCA2. One of the reasons for #mammary_tumors is mutations of the tumor suppressor gene, BRCA2. https://t.co/ucJ1oetabt

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