Research/Areas of Interest:
DNA repair, DNA damage tolerance, molecular biology, Drosophila genetics, aging, mutagenesis
Education
- PhD, Massachusetts Institute of Technology, Cambridge, United States, 2001
- BA, University of Colorado Boulder, Boulder, United States, 1994
Biography
The McVey laboratory studies molecular mechanisms of DNA repair, recombination, and DNA damage tolerance using Drosophila melanogaster as a model system. The wealth of tools available in the Drosophila system allows us to make rapid progress towards identifying conserved proteins and pathways that impact on DNA stability and genome evolution.
One focus in the lab probes the mechanisms by which cells repair DNA double-strand breaks, with an emphasis on alternative end joining. Alternative end joining is error-prone and is frequently used by cancer cells, making it a potential therapeutic target. We have proposed a novel model for alternative end joining and identified DNA polymerase theta as a key player in this type of break repair. Current efforts in the lab are focused on testing this model and determining how polymerase theta acts with other proteins to promote alternative end joining. This work is funded by the National Science Foundation.
We are also interested in ways that cells tolerate damage when copying their DNA. Decades of research in many labs have identified three primary strategies: (1) bypassing DNA damage using mutagenic translesion polymerases, (2) repriming DNA replication downstream of the damage, and (3) switching to an undamaged template for copying. We have shown that fruit flies use translesion synthesis as their primary strategy in tissues undergoing rapid cell division, similar to some cancer cells. The goal of current projects in the lab is to elucidate how damage tolerance is regulated in these tissues and the consequences of inhibition of translesion synthesis. This work is funded by the National Institutes of Health.
We also have a number of recent or ongoing collaborative projects:
- Mechanisms by which the obligate anaerobic bacterium Parabacteroides distasonis promotes healthspan and lifespan in Drosophila (in collaboration with the Crott lab at Boston University, funded by the National Institute on Aging)
- How the antidepressant sertraline causes oxidative DNA damage that can be ameliorated with vitamin C supplementation (in collaboration with the Levin lab at Tufts)
- Using DNA damage as a biomarker of stress in wild birds (in collaboration with the Romero lab at Tufts)
One focus in the lab probes the mechanisms by which cells repair DNA double-strand breaks, with an emphasis on alternative end joining. Alternative end joining is error-prone and is frequently used by cancer cells, making it a potential therapeutic target. We have proposed a novel model for alternative end joining and identified DNA polymerase theta as a key player in this type of break repair. Current efforts in the lab are focused on testing this model and determining how polymerase theta acts with other proteins to promote alternative end joining. This work is funded by the National Science Foundation.
We are also interested in ways that cells tolerate damage when copying their DNA. Decades of research in many labs have identified three primary strategies: (1) bypassing DNA damage using mutagenic translesion polymerases, (2) repriming DNA replication downstream of the damage, and (3) switching to an undamaged template for copying. We have shown that fruit flies use translesion synthesis as their primary strategy in tissues undergoing rapid cell division, similar to some cancer cells. The goal of current projects in the lab is to elucidate how damage tolerance is regulated in these tissues and the consequences of inhibition of translesion synthesis. This work is funded by the National Institutes of Health.
We also have a number of recent or ongoing collaborative projects:
- Mechanisms by which the obligate anaerobic bacterium Parabacteroides distasonis promotes healthspan and lifespan in Drosophila (in collaboration with the Crott lab at Boston University, funded by the National Institute on Aging)
- How the antidepressant sertraline causes oxidative DNA damage that can be ameliorated with vitamin C supplementation (in collaboration with the Levin lab at Tufts)
- Using DNA damage as a biomarker of stress in wild birds (in collaboration with the Romero lab at Tufts)