Novel Mechanisms for DNA Damage and Repair
Repair of UV-induced DNA damage is central to the prevention of a number of adverse conditions such as melanoma, but in most cases the mechanism of such DNA repair is not well understood at a molecular level. Under normal cellular conditions, the major DNA photoproducts of UV irradiation are cyclobutane pyrimidine dimers (TT, CT, and CC dimers) and 6,4-photoproducts, while 5-thyminyl-5,6-dihydrothymine is a minor product. This typically minor UV photoproduct becomes the major UV photoproduct under certain conditions, however, including the conditions that exist in bacterial spores (thus the common name is spore photoproduct, SP). Remarkably, the formation of spore photoproduct is correlated with the unusually high resistance of bacterial spores to UV irradiation, and this resistance arises in part from the novel DNA repair enzyme that repairs SP. The overall goals of this project include investigating the mechanism by which the repair enzyme, SP lyase, recognizes and repairs SP. In addition, we are interested in probing the mechanism by which SP is formed at the expense of cyclobutane pyrimidine dimers.
Biochemistry, Bioinorganic, Biophysical, Inorganic