Mutagenesis and DNA repair
We have determined the structures of a number of chemical lesions in DNA, including two important lesions, O(6)-methyl guanine (View paper) and 8-oxoguanine (View paper). We were able to analyse the data to elucidate structural basis of specific mutations caused by chemical damage to DNA at the molecular level. We have also investigated the origin of the recognition of mismatched and mutagenic bases by DNA repair enzymes. With Prof. Laurence Pearl we elucidated the structural basis of specific base-excision repair by uracil-DNA glycosylase (UDGase) (View paper) and the related enzyme MUG (View paper). UDGase is of interest as a target for antiviral therapy. These essential enzymes reverse the damage that is caused to DNA by oxidation of cytosine bases. Remarkably they recognize the absence of just a single methyl group on the nucleobase to initiate excision repair. This work has implications in cancer and ageing.