Valine 1532 of human BRC repeat 4 plays an important role in the interaction between BRCA2 and RAD51

► Analysis of the functions of BRC repeat 4 of BRCA2 between mammalian species. ► The V1532I substitution in human BRC4 strengthens its interaction with RAD51. ► V1532I interferes with RAD51 oligomerization more than wild-type BRC4. ► The V1532F mutant in breast cancer patients reduces interaction with RAD51. The breast cancer susceptibility protein BRCA2 is essential for recombinational DNA repair. BRCA2 specifically binds to RAD51 via eight BRC repeat motifs and delivers RAD51 to double-stranded DNA breaks. In this study, a mammalian two-hybrid assay and competitive ELISA showed that the interaction between BRC repeat 4 (BRC4) and RAD51 was strengthened by the substitution of a single BRC4 amino acid from valine to isoleucine (V1532I). However, the cancer-associated V1532F mutant exhibited very weak interaction with RAD51. This study used a comparative analysis of BRC4 between animal species to identify V1532 as an important residue that interacts with RAD51. cRAD51physically interacts with cRAD51 by two hybrid(View interaction) fBRC4physically interacts with cRAD51 by two hybrid (View interaction) cBRC4physically interacts with cRAD51 by two hybrid (View interaction) hBRC4physically interacts with hBRC4 and hRAD51 by competition binding (View Interaction 1, 2) hBRC4physically interacts with cRAD51 by two hybrid (View interaction) hBRC4binds to hRAD51 by enzyme linked immunosorbent assay (View interaction)