BRCA2 is an Essential Component of the Rad51-Dependent DNA Repair Complex
Final rept. 1 Jul 2001-30 Jun 2002
CALIFORNIA UNIV BERKELEY LAWRENCE BERKELEY LAB
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The BRCA2 gene is associated with hereditary tendency to breast cancer. Mutations in BRCA2 cause a dominantly inherited predisposition to breast cancer. Recent evidence has indicated that BRCA2 protein plays a role in genome stability and in DNA repair mediated by homologous recombination. The BRCA2 protein has been shown to physically interact with Rad5l, the key protein for DNA recombinational repair. In these BRCA2-deficient cells, formation of Rad5l foci is severely impaired. The evidence for the functions of BRCA2 in DNA repair has suggested a new concept for their role in predisposition to breast cancer. BRCA2 consists of two Rad5l-binding domains, eight BRC repeats and a C-terminal region. These eight conserved BRC repeats designated as BRCl to BRC8, located in the central portion of the protein, are encoded by exon 11 and cover nearly a third of the protein. To demonstrate that BRCA2 is an essential component of the Rad5l-dependent DNA repair complex and understand how BRCA2 regulates homologous recombinational repair HRR, we have made construct of BRCl-4, BRC5-8 and BRCl-8 fragments of BRCA2 and to determine how it would affect the complex formation of Rad5l paralogs and in vitro biochemical activities of Rad5l.
- Genetic Engineering and Molecular Biology
- Medicine and Medical Research