The long-term objectives are to understand the genetic and molecular regulation of genome stability and DNA recombination. Mitotic recombination occurs primarily in response to DNA damage and can directly repair DNA damage. Recombination between repeated sequences is important for both generating and maintaining sequence diversity. Recombination between repeats must be regulated as it has the potential to cause lethal rearrangements. Recombination between repeats is recognized as an important mechanism of mutation in human diseases and is correlated with tumor growth. The genetic regulation of mitotic recombination will be studied using Saccharomyces cerevisiae as a model system. The proposed experiments investigate the number of pathways of mitotic recombination between repeats.
The specific aims of the proposal are: 1) An examination of the role of RAD genes which are involved in DNA repair in specific recombination events in mitosis. 2) Characterization of novel mutants which suppress mitotic recombination. 3) Examination of the molecular events in repeat recombination using a substrate to test different models of pairing in double-strand break stimulated recombination. 4) Study of the role of the excision repair gene RAD1 in meiotic recombination. 5) Study of novel mutations that are synthetically lethal in a hpr1 strain to identity genes involved in mitotic recombination. 6) Purity and characterize the biochemical activities of the HPR1 protein. Absence of the HPR1 protein results in increased mitotic recombination.
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