Role of Histone Modifications in DNA Double Strand Break Repair in Yeast

University Of Alaska Anchorage Campus, Anchorage AK

Investigators

Abstract

The goal of this research is to further our understanding of how covalent histone modifications facilitate the process of DNA repair. One of the early signals of certain types of DNA damage is phosphorylation of histone H2A at the site of the lesion, testifying to an important role of chromatin structure in the detection of damage and/or its repair. Histone acetylation has been shown to facilitate transcription and recombination in many different species, presumably via chromatin decondensation as well as targeting of factors that recognize acetylated nucleosomes. It is hypothesized that histone acetylation will have an analogous role(s) in facilitating DNA repair. This project will use a combination of genetics and in vivo chromatin analysis in the yeast S. cerevisiae to directly test the roles of combinatorial histone H2A modifications in the process of double strand break (DSB) repair. The project has two specific aims: 1. To determine the roles of specific C-terminal and N-terminal residues of histone H2A in DSB repair in vivo. 2. To identify and characterize other modifications of histone H2A required for DSB repair. In addition to increasing our knowledge of the relationships between different histone modifications and DNA repair, a critical aspect of this project is to provide educational research opportunities to graduate and undergraduate students at the University of Alaska-Anchorage. The experiments described in this proposal represent research projects for Ph.D., M.S., and B.S. students, and the budget includes direct support for a graduate student. Also, this laboratory has a unique opportunity to draw Alaska Natives into the fields of basic cell and molecular biology.