DNA Damage and Genetic Instability

The focus of the DNA Damage and Genetic Instability program is to understand how covalent modification of DNA by endogenous and environmental agents alters the biological processing of DNA (replication and repair). This interactive group of investigators uses chemical synthesis, structural biology, bioanalytical chemistry, polymerase enzymology, and molecular and cellular biology to achieve these goals. Active areas of research include the synthesis of site-specifically modified oligonucleotides, the mechanism of DNA modification by potential mutagens, the conformations of the carcinogen-containing oligonucleotides, structure of carcinogen-modified DNA bound to Y-family DNA polymerases, the mechanism of lesion bypass by Y-family DNA polymerases, bacterial and mammalian mutagenesis, and DNA-based biomarker development. Specific projects include DNA adducts derived from oxidative damage to lipids (4-hydroxynonenal and malondialdehyde), heterocyclic amines (2-amino-3-methylimidazo[4,5-f]quinoline (IQ)), and alkylating agents (butadiene, vinyl chloride, methylating agents, and aflatoxin B1). A rather unique aspect of this work that distinguishes the Vanderbilt group from other groups working in the area is the availability of site-specifically modified oligonucleotides containing a wide variety of DNA adducts on a scope that is not currently matched anywhere else.

For further detail on research programs focusing on DNA Damage and Genetic Instability, see the individual faculty pages of Egli, Guengerich, Harris, Marnett, Rizzo, and Stone.