The adduction of DNA by mutagenic chemicals represents the initiating step in chemical carcinogenesis. Our laboratory seeks to understand how mutagenic chemicals perturb DNA structure and conformation, and how this alters the biological processing of DNA during replication and repair. NMR spectroscopy is used to delineate molecular conformations and dynamics in solution. X-ray crystallography monitors the structures of protein-DNA complexes related to replication and repair. Structural data is correlated with biochemical data obtained in vitro and site-specific mutagenesis data obtained using bacterial and mammalian cells, to develop structure-activity relationships.
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