We seek to find new paradigms in the maintenance of the eukaryotic genome. While classical studies on the DNA damage response have focused on DNA, we are now addressing the role of chromatin in genome integrity. There are two major modes of chromatin modification: ATP-dependent chromatin remodeling and histone modification. We are interested in understanding how these chromatin-modifying activities are involved in various aspects of the DNA damage response, and how alterations in these chromatin-modifying activities lead to cancer.
We use the budding yeast as a model system, taking advantage of its powerful genetics and well-developed biochemical tools. Our current research focuses on a novel and evolutionarily conserved class of ATP-dependent chromatin remodeling complexes called the INO80 class. The study of the INO80 complex has led us to two main areas of research in the lab: the DNA damage response, and the regulation of nuclear actin.