David T. Long, "The role of homologous recombination and BRCA1 in DNA crosslink repair"
Dec 06, 2012 (Thu) | 12:00 PM -2:00 PM
Clark Center Auditorium, 318 Campus Drive : Stanford, CA
Abstract: Components of the DNA damage response have been linked to various genetic disorders that are typified by hypersensitivity to DNA damaging agents and cancer predisposition. One such disease, Fanconi anemia (FA), has extensive genetic overlap with hereditary breast cancer syndromes (BRCA). Like FA cells, many breast cancers are sensitive to DNA interstrand cross-links (ICLs), suggesting the two diseases involve overlapping repair defects. ICLs are extremely toxic lesions whose repair involves the formation of a DNA double-strand break (DSB). Using Xenopus egg extracts, I showed that ICL-generated breaks are repaired by homologous recombination. These results established the first system that recapitulates homology-directed repair of a DSB in vitro. Recently, I used this system to investigate one of the more enigmatic recombination factors, BRCA1. Surprisingly, I found that BRCA1 performs a novel function during ICL repair that is distinct from its established role in recombination. These studies establish Xenopus egg extracts as a powerful tool to elucidate the mechanisms whereby DNA damage leads to genomic instability and cancer.
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