A New Mechanism for the Breast Cancer Gene BRCA1

Using the proteomic peptide library approach, we have identified a new functional domain involved in the development of breast cancer. The BRCA1 breast cancer gene contains a tandem pair of BRCT domains that function together a unit to bind to specific phosphorylated proteins involved in detection and repair of DNA damage. Eighty percent of women who inherit mutant forms of the BRCA1 protein develop breast cancer and 65% develop ovarian cancer. Many of these mutations eliminate the phosphopeptides-binding function of the tandem BRCT domains, preventing propogation of the DNA damage signal. The result is that DNA damage is not repaired before the onset of the next cell cycle, causing the accumulation of additional mutations, and ultimately causing cancer. Absence of BRCA1 activity is detrimental to healthy cells. However, disruption of the tandem BRCT domains of BRCA1 that the lab has identified may allow tumor cells to be more susceptible to anti-cancer drugs.