The long term goal of
our research program is to elucidate the molecular mechanisms of DNA
adduct-induced chemical carcinogenesis. Aromatic amines are well-known
environmental human carcinogens and their DNA adduct formation has been
confirmed in various human tissues. Arylamine adducts in DNA exist in
three well-defined conformations: stacked (S), external B-type (B), and
wedge (W). The conformation depends on the location of the carcinogen
moiety in the DNA molecule, and the population ratios of the types under
physiological conditions are sequence-dependent. We are currently working
to define adduct conformation and examine their specific effects on repair
and replication. To meet this challenge, we employ SPR, DSC, NMR, and CD
procesures, a powerful suite of biophysical methodologies. The results
will help us gain a better grasp on the protein-DNA interactions involved
in human NER and trans-lesion synthesis, which have important implications
for resolving the molecular details of cancer etiology. Undergraduate
student is expected to be participated in preparation and NMR/CD
characterization of a specific arylamine adduct.
