Analysis of changes in genome structure by homologous recombination.

摘要

Changes in genome structure often occur during cancer or evolution. These alterations can be initiated by DNA double-strand breaks (DSBs) that misrepair through nonallelic homologous recombination (NAHR). NAHR can generate many types of rearrangements, including deletions, duplications, inversions, translocations, with the possibility of altering gene expression of the organism. In this study, I am interested in understanding how NAHR between dispersed repetitive sequences operates. In Chapter 2, I develop a novel assay to measure all the outcomes of a genome-wide NAHR competition between Saccharomyces cerevisiae Ty retrotransposon elements. In Chapter 3 and 4, I investigate how sequence identity, chromosomal position, and repair pathway influences the NAHR competition. In Chapter 5, I examine how well NAHR competes with allelic HR. My findings, detailed in the following chapters, impact a number of distinct fields including homologous recombination and genome evolution.