Functional Analysis of Breast Cancer Susceptibility Gene BRCA2

摘要

Germline mutations in the BRCA2 gene lead to an increased lifetime risk for breast and ovarian cancer, and pancreatic, prostate, and male breast cancers. Although the BRCA2 protein has been reported to play a role in DNA repair, the normal cellular function of the BRCA2 gene is still mostly unknown. In this report, we demonstrate that cellular levels of BRCA2 protein are diminished following UV irradiation, suggesting that regulation of BRCA2 during DNA repair is complex. In work based on a previous collaborative observation, we also explore a potential interaction between BRCA2 and Braf35 proteins and provide evidence that this interaction does not occur in cells. Additionally, we show that among the human homologs of the RecA family of DNA repair proteins, BRCA2 binds exclusively to Rad5 1. Regulation of BRCA2 expression by p53 was assessed and BRCA2 levels were found to be unaffected by p53. We also report the construction of a series of epitope-tagged BRCA2 constructs that will be used to identify potential BRCA2-interacting proteins. These efforts will help provide a more complete picture of the normal cellular role of the BRCA2 gene.