Isw2 and Ino80 Complexes Regulate the Ribosomal DNA Locus and DNA Break Repair Choice

Abstract

To achieve the high degree of compaction required to fit the eukaryotic genome into a nucleus, DNA has evolved to be organized in a structure referred to as chromatin. Chromatin involves the tight interaction of DNA with histone octamers known as nucleosomes. Because this association between DNA and nucleosomes inhibits DNA-dependent processes, chromatin structure is carefully regulated to facilitate transcription of RNAs from the DNA template, repair of DNA damage, and replication of the genome. ATP-dependent chromatin remodeling factors use the energy of ATP hydrolysis to modify specific features of chromatin structure. In this dissertation, I focus on elucidating biological functions of the Saccharomyces cerevisiae remodeling factors Isw2 and Ino80. I show that these complexes are targeted to the yeast ribosomal DNA locus, where they modify local chromatin structure and regulate replication initiation from this genomic locus and changes of the size of the highly repetitive rDNA array. In addition, I show evidence supporting possible roles for Isw2 and Ino80 in regulating the balance between two mechanisms of repair of DNA double strand breaks. In sum, my work establishes novel functions for these chromatin remodeling factors at a uniquely repetitive and important part of the eukaryotic genome and in a process that is crucial for genome stability.