Structural biology of DNA repair and genome maintenance
DNA damage arising from exposure to environmental toxins and cellular metabolites thwarts DNA replication and leads to genome instability, cell death, and diseases including cancer. Our laboratory uses the tools of structural biology and biochemistry to investigate molecular mechanisms of proteins involved in repairing DNA damage and maintaining replication fork progression. We primarily use X-ray crystallography as a starting point to understand how these proteins recognize and manipulate DNA structure to carry out their particular functions.
Current work focuses on base excision repair of DNA alkylation damage by DNA glycosylases, repair of stalled replication forks by structure-specific DNA translocases, and the coordination of DNA unwinding and synthesis during eukaryotic replication.
The long-term goals are to understand the fundamental processes underlying genome maintenance and to develop new therapeutic strategies that target genetic diseases.