Regulation of chromatin structure in genome stability

Thesis (Ph.D.)--University of Washington, 2016-03In eukaryotic cells, DNA is tightly packaged into chromatin. Because chromatin is inhibitory to DNA-binding proteins, it must be modified so that necessary DNA-protein interactions can occur. Chromatin structure can be modified or altered by chromatin regulators. One class of chromatin regulators is the ATP-dependent chromatin remodeling factor family. Chromatin remodeling enzymes utilize ATP hydrolysis to alter chromatin structure and thus affect many DNA-dependent processes. Mutations in these complexes can cause disease and cell death, signifying their importance. Here I use Saccharomyces cerevisiae as a model organism to characterize the roles of chromatin structure and remodeling factors in essential biological processes. In this study, I show that budding yeast remodeling factors Isw2 and Ino80 act in opposition to checkpoint activators and promote accessibility of chromatin during replication stress. I also suggest novel roles for these enzymes in telomere homeostasis and rRNA transcriptional regulation. Finally, I show that nucleosome occupancy is a novel parameter for origin activities and that a chromatin regulator is likely responsible for establishing occupancy at origins. Taken together my work demonstrates the importance of chromatin regulation in cellular mechanisms that are crucial for genome integrity