Functional Study of the Human BRCA2 Tumor Suppressor
Annual summary rept. 1 Aug 2002-31 Jul 2005
DANA-FARBER CANCER INST BOSTON MA
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My research is focused on the BRCA2 protein, whose mutations have been implicated in the development of breast, ovarian, male breast, prostate, pancreatic cancers and Fanconi anemia. It is intended to elucidate some of the biological functions of BRCA2 andor regulation of its in vivo function through generationutilization of new reagents and identification of new BRCA2 interacting proteins. During the years of grant support, I generated an array of BRCA2 antibodies and identifiedcloned a novel protein, PALB2, as a major nuclear partner and localizer of BRCA2. I have established that PALB2 is required for BRCA2 nuclear presence and its functions in homologous recombinational repair of double-strand breaks and intra-S phase damage checkpoint control. Importantly, BRCA2PALB2 interaction is disrupted by multiple cancer-associated BRCA2 mutations. My results indicate that PALB2 is essential for the tumor suppressing functions of BRCA2 and may be a new tumor suppressor gene in its own right.
- Medicine and Medical Research