Functional testing of breast cancer susceptibility genes

Rationale: The breast cancer susceptibility genes BRCA1 and BRCA2 encode proteins which enable mammalian cells to repair DNA double strand breaks (DSBs) via homologous recombination (HR). Tp53 is mutated in Li-Fraumeni patients with a high incidence of mammary carcinoma. The Tp53 gene product p53 monitors the fidelity of HR in addition to its growth-regulatory functions. Moreover, recent data suggest that activity changes of other DSB repair factors (ATM, Chk2, Rad51, Rad54, Xrcc2, Xrcc3, Lig4) also play a role during the development of both familial and sporadic forms of mammary carcinoma. Methods: Successful D…