The Tomkinson laboratory is interested in the interlinked pathways of DNA replication, DNA repair and genetic recombination, which function together to maintain genomic stability in eukaryotes. Defects in these pathways can lead to a decrease in cell viability, an increase in the frequency of carcinogenesis and an increase in the transmission of altered genetic information to the next generation. We have chosen to focus on eukaryotic DNA joining enzymes, DNA ligases, since mutations in the DNA ligase genes of prokaryotes and lower eukaryotes cause genetic instability. Three DNA ligase genes have been identified in the human genome. Since DNA joining is an essential common step in DNA replication, genetic recombination and most DNA repair pathways, the study of DNA ligases has and will continue to provide insights into the molecular mechanisms of these different DNA transactions. A major goal of these studies is to determine the cellular roles of the different mammalian DNA ligases and to use these enzymes as probes to elucidate the molecular mechanisms of replication, repair and recombination pathways.
