DNA Replication, Recombination and Repair; Genome Integrity; Molecular and Cellular Biology; Molecular genetics; Protein Function and Structure
In my laboratory, we are interested in the general problem of maintaining genome stability. To this end, we focus on two distinct aspects of genome stability: 1) the roles of mismatch (MMR) proteins in multiple pathways for DNA repair and 2) the manner in which regulation of dNTP pools, through the regulation of ribonucleotide reductase (RNR) activity, impacts genome integrity.
1) MMR proteins recognize many different types of DNA lesions and then target the lesion for the appropriate repair pathway. We are interested in the mechanism(s) by which recognition of a lesion is translated into the appropriate DNA repair pathway, using the yeast Saccharomyces cerevisiae as a model system. Is it through differential protein-nucleic acid or protein-protein interactions? To address these questions as well as the regulation of DNA repair pathway selection, we use a combination of genetic, biochemical and biophysical approaches.
2) RNR activity modulates the level of dNTPs that are available in a cell at a given time. Higher levels of dNTPs lead to higher mutation rates. We are interested in the various ways in which misregulated dNTP pools might affect cellular metabolism and affect the stability of the genome.