GENOME STABILITY IN RAD MUTANTS

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Homologous recombination is an important biological response to DNA damage by radiation and chemicals. However, recombination must be controlled because deleterious genome rearrangements results from recombination between repeated sequences. Observations in several eukaryotic systems have established the recombination between sequences under 250 bp in length is tightly controlled. This is essential for the maintenance of genome stability because the majority of repeated sequences are short. In this laboratory, several radiation sensitivity (RAD) genes have been shown to control recombination between short sequences in the yeast S. cerevisiae, and that this control is distinct from the control of recombination between longer sequences. The further investigation of this selective control is the goal of the proposed research program. Novel deletion and translocation assays will be employed to determine the role of additional RAD genes in the control of short-repeat recombination (SRR). The role of these genes in double- strand break (DSB) processing, heteroduplex formation, and joint molecular formation during SRR will be analyzed with a novel DSB induced gene replacement assay. Together these genetic and physical studies will provide unique insight into how genomic integrity is maintained in the wake of DNA damage.