Research in my laboratory is focused on understanding the molecular mechanism of DNA repair and mutagenesis in eukaryotes and the roles of these processes in cancer associated with both spontaneous DNA damage and that caused by environmental carcinogens.
The human hereditary disease xeroderma pigmentosum (XP) is characterized by defective DNA repair and an increased predisposition to cancer caused by environmental agents. XP is genetically complex and is represented by multiple unlinked genes. We have used cloned human genes as probes to isolate homologous mouse genes in order to generate mouse mutant models for investigating the molecular pathology of XP, and the relationships between defective DNA repair and cancer predisposition.
We have identified a gene in humans that encodes a novel DNA polymerase (one of multiple such novel polymerases recently discovered) which is involved in the generation of spontaneous mutations in cells. The physiological function(s) of this novel DNA polymerase is presently unknown and is being investigated in mutant mice generated by conventional and conditional knock-out strategies.
The yeast Saccharomyces cerevisiae is a powerful eukaryotic model system because of its genetic and molecular versatility and because yeast genes for DNA repair and mutagenesis are highly conserved in humans. Present studies are focused on understanding newly discovered relationships between DNA repair and functions of the 19S regulatory complex of the proteasome.
