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Albert M. ChehProfessor - E-mail - Curriculum vitae My research focuses on the mechanisms by which polycyclic aromatic
hydrocarbon diol epoxides (PAH DEs, major carcinogenic components of
cigarette smoke) damage DNA and initiate mutagenesis and carcinogenesis.
Recently we have focused on the behavior of members of the novel Y-family
of bypass DNA polymerases when they encounter PAH DE addition products
(adducts) in DNA. We identify the types of mistakes (misincorporations)
made by these polymerases as they bypass PAH DE adducts, to help elucidate
the mechanisms of early steps in PAH DE carcinogenesis. We study the
behavior of the enzymes at different stereoisomeric adducts to shed
light on the nature of the enzyme active sites and the enzymatic mechanisms
leading to misincorporation. This work is being done in close collaboration
with the Laboratory of Bioorganic Chemistry, NIDDK, NIH. Another research
area has been the development of rapid methods for determining the
spectrum of DNA mutations produced by carcinogens. We correlate these
mutational spectra with the degree of carcinogenicity exhibited by
different PAH diol epoxides. |