Endogenous free radicals and environmental agents such as ionizing radiation induce DNA double-strand breaks. The repair of these breaks is crucial for the maintenance of genome stability. Two distinct pathways help eliminate DNA double-strand breaks. In homologous recombination (HR), the repair of a broken DNA molecule requires an intact homologous duplex to direct the process. Alternatively, a pathway known as non-homologous DNA end joining (NHEJ) simply rejoins the ends of the broken DNA molecule. Our research efforts focus on delineating the mechanism of homology-directed repair of DNA double-strand breaks in the yeast Saccharomyces cerevisiae and humans.