We focus on genome stability and chromosome metabolism using the yeast, Saccharomyces cerevisiae, which has served as a cornerstone in current understanding of eukaryotic genetics. Because genome organization, enzymatic processes, and genetic controls are often closely related in yeast and humans, our results are often directly applicable to human disease. Central to our studies are recombination between homologous and related DNAs, errors in replication leading to mutations via slipage between tandem or distant repeats, identification of spontaneous and genotoxicant-sensitive at-risk sequences in the genome, the impact of mismatch repair on recombination and mutation, abnormal chromosome segregation (anueploidy) in mitosis and meiosis, DNA repair, and cell signaling in response to DNA damage.

We have applied our findings to developing methods for isolating and characterizing human genes. In one approach, human expressed genes are isolated that perturb chromosome metabolism in yeast or bacteria, thereby providing the means to functionally characterize human genes. Our studies on recombinational repair of DNA double-strand breaks has yielded a new approach for the direct high-fidelity isolation of large segments of specific human DNA fragments and entire genes as yeast artificial chromosomes.