Research in our group explores mechanisms of DNA repair and the consequences for carcinogenesis. Our research employs a broad range of investigations, ranging from fundamental biochemical studies and proteomics through cellular biology, to genetically engineered mouse models having impaired pathways of repair and mutagenesis.
Biochemical Mechanisms of DNA Crosslink Repair
Some research in the laboratory examines the biochemical mechanism of repair of cross-links between DNA strands. Chemicals that produce cross-links are particularly destructive of genome function, and so they are widely used in cancer chemotherapy.
DNA Polymerase zeta (REV3L)
Our group has generated mouse models with specific deficiencies in DNA polymerase zeta. These models reveal that the enzyme is critical for maintaining chromosome stability and limiting tumorigenesis.
|Rev3L deletion in p53 mutant mice leads to increased cancer incidence and shortened lifespan.|
DNA Polymerase theta (POLQ)
Our scientists have also identified and are studying the function of other DNA processing enzymes. We have found that the specialized DNA polymerase POLQ plays a major role in defending cells against x-rays and other agents that cause DNA strand breaks.
|Micronuclei, consisting of broken chromosomes, form frequently in POLQ-deficient cells.|
DNA Polymerase nu (POLN)
The POLN enzyme also has unique properties and can bypass complex lesions. We are studying POLN knockout mice, and proteins interacting with POLN.
|Testis section from POLN knockout mouse.|
DNA Helicase HELQ
We have also identified a DNA helicase, called HELQ, which functions in repair of damaged DNA by cooperating with recombination proteins. Defects in HELQ cause sensitivity to DNA interstrand crosslinking agents.