Biological Chemistry and Molecular Pharmacology
Vertebrate cells employ intricate mechanisms to duplicate their genomes and guard against DNA damage. Xenopus laevis frog egg extracts have an extraordinary capacity to recapitulate these processes in the test tube, allowing us to elucidate the underlying mechanisms. Using this system, we study how the replicative DNA helicase unwinds DNA (Fu et al., Cell, 2011), how it is unloaded from chromatin during replication termination (Dewar et al., Nature 2015), and how its re-loading is prevented to limit replication to a single round per cell cycle (Havens et al., Mol Cell, 2009). Using DNA templates containing chemically defined DNA lesions, we also examine the mechanism of replication-coupled repair, including DNA interstrand cross-link repair (Raschle et al., Cell, 2008) and DNA protein cross-link repair (Duxin et al., Cell 2014). In the last few years, we have begun to study replication and repair at the single molecule level (Yardimci et al., Nature, 2012; Graham et al., Mol Cell, 2016). Finally, we examine how defects in replication-associated repair cause Fanconi anemia and other cancer pre-disposition syndromes (Long et al., Mol. Cell 2014; Knipscheer et al., Science 2009).
We use ensemble and single molecule approaches in frog egg extracts to study mechanisms of DNA replication and DNA repair.
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