The functions of breast cancer susceptibility gene 1 (BRCA1) product and its associated proteins

About half of the familial breast cancer cases are found to bear mutations in the breast cancer susceptibility gene 1 (BRCA1). The majority of BRCA1 m utations produce a truncated protein and BRCA1-associated breast tumors exh ibit a number of defined tumor phenotypes, The function of BRCA1 has been e xamined in gene knockout mice in which the nullizygous mice die early in ut ero, but this lethality can be partially rescued by a nullizygous p53 mutat ion. Wild-type BRCA1 protein binds to a number of cellular proteins, includ ing DNA repair protein Rad51, tumor suppressor p53, RNA polymerase II holoe nzyme, RNA helicase A, CtBP-interacting protein, c-myc, BRCA1-associated RI NG domain protein (BARD1), BRCA2 protein, etc, These proteins likely mediat e the involvement of BRCA1 in DNA repair, transcriptional transactivation, and cell cycle control. Overall, BRCA1 protein may act as a converging vehi cle for cell regulatory proteins to associate with. Therefore, mutations in BRCA1 may affect the composition of these complexes on which dysregulation of cellular functions with eventual development of malignancy is expected.