We are investigating the unique metabolic events associated with meiotic recombination and the repair of chromosomes following exposure to DNA damaging events in the budding yeast Saccharomyces cerevisiae. Many genes necessary for the repair of DNA double strand breaks (DSB) are also required for the successful completion of meiosis, suggesting that these processes have similar molecular mechanisms. The RAD52 gene plays a prominent role in meiosis and in repair of DSB's and is under active investigation. An additional yeast gene, RNC1, has been cloned and sequenced in the lab and shown to influence recombination and repair in a RAD52-dependent manner. Recent work has focused on: 1. biochemical study of nuclease protein purified from overexpressing E. coli and yeast cells; 2. the physiological effects of expression of mutant nuclease enzymes with altered GTPase activities in wild-type and repair-deficient yeast cells; 3. characterization of several recently identified yeast genes whose expression is lethal in rad52-deleted strains (yeast strains which cannot repair DSB's); 4. analysis of a newly identified class of mutant yeast cells which are deficient in DSB repair and/or mitotic recombination.
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