New insights into the biological function of BRCA2 from its structural interactions

Excerpt

Around 50% of all familial breast and ovarian cancers are due to mutations in BRCA1 and BRCA2. Germline mutations in the BRCA2 gene are associated with an increased susceptibility to breast cancer (in both males and females) and they also confer an increased risk of early onset ovarian, prostate, and pancreatic cancer. The biological function of BRCA2 in the cell is still uncertain, although there is increasing evidence for a role in the repair of DNA by homologous recombination. BRCA2 and RAD51 (a homolog of the baterial recombination protein RecA) both co-localise to nuclear foci thought to be sites of DNA damage and repair and these nuclear foci fail to form in BRCA2 deficient cells. Loss of BRCA2 leads to error prone repair of double strand DNA breaks and in dividing cells can lead to chromosomal abberations and loss of genetic information. Compelling evidence of a more direct role for BRCA2 in DNA repair is provided by two recent studies investigating some of the protein's structural interactions. …