Multiple possible sites of BRAC2 interacting with DNA repair protein RAD51

✍ Scribed by Toyomasa Katagiri; Hiroko Saito; Akira Shinohara; Hideyuki Ogawa; Nanao Kamada; Yusuke Nakamura; Yoshio Miki

• Publisher: John Wiley and Sons
• Year: 1998
• Tongue: English
• Weight: 167 KB
• Volume: 21
• Category: Article
• ISSN: 1045-2257
• DOI: 10.1002/(sici)1098-2264(199803)21:3<217::aid-gcc5>3.0.co;2-2

✦ Synopsis

To investigate the biological consequences of aberrant BRCA2 protein during mammary carcinogenesis, we attempted to identify proteins that normally interact with BRCA2. By using a yeast two-hybrid system with a hybrid protein that contained residues 639-1,508 of BRCA2 protein fused to the GAL4 DNA-binding domain, we isolated five independent cDNA clones that encoded parts of RAD51 protein, a human homolog of bacterial RecA. In vitro experiments using anti-RAD51 antibody confirmed interaction of BRCA2 with RAD51. The RAD51-binding region of BRCA2 detected in the present study was distinct from the region reported recently. Further studies using smaller portions of BRCA2 defined at least two additional RAD51-binding domains, residues 982-1,066 and 1,139-1,266. Our results suggest that BRCA2 can interact with RAD51 through multiple sites of BRCA2 and that control of mitotic and meiotic recombination and/or of genomic integrity through binding to RAD51 may be a crucial mechanism by which BRCA2 suppresses abnormal proliferation of mammary cells.