Molecular Basis for BRCA2-mediated DNA Repair and Breast Tumor Suppression
Annual summary, 15 Sep 2006-14 Sep 2007
YALE UNIV NEW HAVEN CT
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In eukaryotes, homologous recombination and the homology-directed repair of DNA double-strand breaks are mediated by the RAD51 recombinase. In catalyzing recombination reactions, RAD51 must first form a right-handed helical filament, termed the presynaptic filament, on single-stranded DNA. Emerging evidence indicates that BRCA2 acts a recombination mediator by promoting the assembly of the RAD51 presynaptic filament. BRCA2 binds DNA and associates with RAD51. Our laboratory has established biochemical systems to examine the recombination mediator function of BRCA2. The main focus of my fellowship project is to define the role of DNA binding in this BRCA2 function. The BRCA2 DNA-binding domain DBD represents a highly conserved region within BRCA2-like molecules and harbors a significant portion of tumor-derived missense mutations, underscoring the importance of addressing the functional significance of this BRCA2 domain.
- Genetic Engineering and Molecular Biology
- Medicine and Medical Research