It is well established that DNA damage results from a variety of endogenous and exogenous sources. As a result, a variety of lesions are introduced disrupting the integrity of DNA. Oxidative damage of DNA has been implicated in disease development, particularly cancer.  To better understand the underlying mechanisms of these biological processes, oxidative damage to DNA and DNA-protein complexes will be evaluated.  Upon selective generation of the C3'-thymidinyl radical under anaerobic conditions, damage products are generated which can be identified using matrix-assisted laser desorption time-of-flight mass spectroscopy and high-performance liquid chromatography. The results obtained indicate that the distribution of damage products is minimally affected by DNA structure, while the stereoselectivity of �repair� relies heavily on the local environment surrounding the site of radical formation.  The methodology developed here will be used to determine the interplay between DNA structure and protein DNA-interactions as they relate to oxidative damage generation.

C3'-DNA damage: Impact of DNA structure on the formation of oxidative damage products

244th National Meeting (2012)

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