Roles of 5-Methylcytosine in the Photochemistry of DNA

University Of California-San Francisco, San Francisco CA

Investigators

Abstract

The goals of this research are twofold. First, efforts will be made to isolate and characterize a number of photoproducts believed to be relevant to achieving a chemical understanding of UVB-induced DNA damage. Cyclobutane dimers, Dewar adducts and (6-4) adducts of 5-methylcytosine with thiamine and cytosine will be sought. Second, it will be determined if the various products isolated in experiments related to goal one are also formed within the context of DNA and in the environment of a cell nucleus. Calf thymus DNA and nuclei and wheat DNA and nuclei will be used for this portion of the work. With this award, the Organic and Macromolecular Chemistry Program is supporting the research efforts of Dr. Martin D. Shetlar of the Department of Pharmaceutical Chemistry at the University of California, San Francisco. Professor Shetlar will focus his work on finding out what happens to mammalian and plant DNA after it absorbs ultraviolet light. In particular, the work focuses on the role of the minor base 5-methylcytosine in mediating damage induced by the absorption of ultraviolet light. The research could have a broader impact in helping to understand the role that UV-induced lesions in DNA might play in the induction of skin cancer and other unwanted biological effects.