Abstract
The genome of a cell is continuously subject to damage. By-products from cell metabolism, irradiation, chemical agents, and ultraviolet light are all environmental factors that cause lesions that can block replication progression. Although cells have adapted checkpoint mechanisms and repair pathways, repair failure can lead to deletions, translocations, and fusions in the DNA. These genomic rearrangements are commonly found in cancer cells. Double-strand breaks (DSBs) are problematic and the most lethal type of damage if not properly repaired. Recent studies by the Haber lab have shown that repair of broken chromosomes is accompanied by a 1000-fold increase in the rate of mutations compared to the events that spontaneously arise during DNA replication. We are now interested in understanding and comparing how the rate and spectrum of mutations change under different DNA damage conditions, which may subsequently provide some insights about DNA repair mechanisms and cancer formation. In this study, it is shown that mitotic gene conversion is more prone to base-pair deletion, which is accompanied by up to 10-fold increase in single-nucleotide deletion. Most mutations are especially prominent to occur at homonuleotide runs. In addition, this paper will discuss double-stranded break repair mechanisms, as well as studies specifically on gene conversion mutagenesis.