THE BRCA2 GENE-PRODUCT FUNCTIONALLY INTERACTS WITH P53 AND RAD51

Germ-line mutations in the human BRCA2 gene confer susceptibility to b reast cancer. Efforts to elucidate its function have revealed a putati ve transcriptional activation domain and in vitro interaction with the DNA repair protein RAD51. Other studies have indicated that RAD51 phy sically associates with the p53 tumor suppressor protein. Here we show that the BRCA2 gene product is a 460-kDa nuclear phosphoprotein, whic h forms in vivo complexes with both p53 and RAD51, Moreover, exogenous BRCA2 expression in cancer cells inhibits p53's transcriptional activ ity, and RAD51 coexpression enhances BRCA2's inhibitory effects. These findings demonstrate that BRCA2 physically and functionally interacts with two key components of cell cycle control and DNA repair pathways . Thus, BRCA2 likely participates with p53 and RAD51 in maintaining ge nome integrity.