We study these questions in genetically-targeted mice using a variety of molecular and biochemical techniques. Specific projects underway in the lab include studying the importance of the BLM and Exo1 proteins in regulating how DNA double-strand breaks are processed. We are also using mouse models and structural biology approaches to test how the BRCA1 tumor suppressor functions at the molecular level. The importance of ubiquitylation in the DNA damage response is another theme, especially focusing on the activity of the SUMO-targeted ubiquitin ligase, RNF4. Finally, through our active partnership with colleagues at the Rutgers Cancer Institute of New Jersey, we are using data from whole-genome sequencing approaches to study how individual mutations in human cancer patients affect DNA repair.