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.
J.M. Buis, J. Cheek, E. Kalliri, J.B. Broderick , "Characterization of an Active Spore Photoproduct Lyase, an Enzyme in the Radical SAM Superfamily." J. Biol. Chem. 2006, 381(36), 25994 - 26003.
Tilak Chandra, Sunshine C. Silver, Egidijus Zilinskas, Eric M. Shepard, William E. Broderick, and Joan B. Broderick, "Spore Photoproduct Lyase Catalyzes Specific Repair of the 5R but not the 5S Spore Photoproduct." J. Am. Chem. Soc. 2009, 131, 2420-2421.
Tilak Chandra, William E. Broderick, and Joan B. Broderick, "Chemoselective Deprotection of Triethylsilyl Ethers." Nucleotides, Nucleosides, and Nucleic Acids 2009, 28, 1016 – 1029.
Sunshine C. Silver, Tilak Chandra, Egidijus Zilinskas, Shourjo Ghose, William E. Broderick, and Joan B. Broderick, "Complete stereospecific repair of a synthetic dinucleoside spore photoproduct by spore photoproduct lyase." J. Biol. Inorg. Chem. 2010, 15(6), 943-955.
Tilak Chandra, William E. Broderick, and Joan B. Broderick, "An Efficient Deprotection of N-trimethylsilylethoxymethyl (SEM) Groups from Dinucleosides and Dinucleotides." Nucleotides, Nucleosides, and Nucleic Acids 2010 29, 132-143.
Biochemistry, Bioinorganic, Biophysical, Inorganic