Research in the Rusche lab focuses on chromatin and its impact on gene expression, genome stability, and chromosome function. One area of research focuses on Sir2 proteins (sirtuins), which deacetylate histones to repress transcription. Because sirtuins require NAD+ for activity, they are proposed to link the processes they regulate with nutrient availability. We are investigating how the functions of yeast sirtuins have shifted over the course of evolution to enable species to develop distinct responses to nutrient stress. Another area of research focuses on the nucleosome-binding protein Sir3, which partners with Sir2. We are reconstructing the steps by which Sir3 evolved through gene duplication from the conserved replication protein Orc1. For our studies, we employ yeasts as model organisms, taking advantage of the powerful classical genetic and contemporary comparative genomic approaches available in these species.