Michelle Hamm, University of Richmond, Richmond, VA
8-oxo-2'-deoxyguanosione (OdG) is an abundant DNA lesion that has been linked to cancer and ageing. It can be removed from double stranded DNA when in a base pair to dC by Fpg and hOgg, two repair glycosylases found in E. coli and humans, respectively. In order to gain insight in to the means of OdG recognition by these two enzymes, we synthesized or purchased three analogues of OdG and tested their activity with Fpg and hOgg. Theses analogues included 8-thio-2'-deoxyguansoine (SdG), 7-methyl-8-oxo-2'-deoxyguanosine (MdG) and 7-deaza-2'-deoxyguanosine (AdG). We found all three were active with both enzymes indicating broad substrate specificity and suggesting that both enzymes recognize their substrate, at least in part, by the absence of a ring parallel lone pair at C8.