The Biological Implications of Damage to DNA Incorporating an 8-Oxodeoxyguanine:Cytosine Basepair

Abstract

DNA damage produced by free radicals is probably the most frequent lesion encountered by cells (Wallace, S.S., Environmental and Molecular Mutagenesis 12, 431–477, 1988 (1)). One of the most common effects is the formation of 7-hydro-8-oxodeoxyguanine due to oxygen radicals interacting with the normal guanine base. Such chemical changes appear to be important in mutagenesis, cancer and aging. We have used computer simulation techniques to model the effect of inclusion of such a modified base within a duplex strand of DNA. We find that such modifications can be stabilized within a normal sequence. The conformation of the modified base relative to the sugar residue depends on many local interactions not accessible to the isolated nucleoside. We have also studied the essential dynamics of both normal and modified sequences and show that there are only subtle changes to the dynamics on inclusion of such a modification.