Interactions between canine RAD51 and full length or truncated BRCA2 BRC repeats.
In humans, mutations in the gene for the breast cancer susceptibility protein BRCA2 affect its interactions with the recombinase RAD51 and are associated with an increased risk of cancer. This interaction occurs through a series of eight BRC repeat sequences in BRCA2. A mammalian two-hybrid assay using individual BRC repeats demonstrated that BRC6 did not bind to RAD51, whereas there was strong (BRC1, 2 and 4), intermediate (BRC8), or weak (BRC3, 5 and 7) binding of other BRC repeats to RAD51. In serial deletion mutation experiments, binding strengths were increased when the C-terminal BRC repeat was removed from BRC1-8, BRC1-5 and BRC1-3. These results may provide an insight into the effects of missense or truncation mutations in BRCA2 in canine tumours.
Division for Animal Research Resources, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima 770-8503, Japan.
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Ochiai
Laboratory of Veterinary Biochemistry, School of Veterinary Medicine, Kitasato University, Aomori 034-8628, Japan.
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Yoshikawa
Department of Biological Resources, Integrated Centre for Science, Ehime University, Shitsukawa, Toon City, Ehime 791-0295, Japan.
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Oonuma
Institute for Genetic Medicine, Hokkaido University, Sapporo 060-0815, Japan.
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Tomioka
Department of Veterinary Physiology, Faculty of Agriculture, Iwate University, Morioka 020-8550, Japan; United Graduate School of Veterinary Science, Gifu University, Yanagido, 1-1, Gifu 501-1193, Japan.
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Hashizume
Institute for Genetic Medicine, Hokkaido University, Sapporo 060-0815, Japan. Electronic address: mmorimat@igm.hokudai.ac.jp.
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Morimatsu
D000818:Animals; D024682:BRCA2 Protein / Q000235:genetics* / Q000378:metabolism; D004283:Dog Diseases / Q000201:enzymology / Q000235:genetics*; D004285:Dogs; D005260:Female; D024522:Genes, BRCA2; D015674:Mammary Neoplasms, Animal / Q000201:enzymology / Q000235:genetics*; D020125:Mutation, Missense; D051135:Rad51 Recombinase / Q000378:metabolism*; D020079:Terminal Repeat Sequences
D024682:BRCA2 Protein; D051135:Rad51 Recombinase