Molecular Mechanisms of Genetic Recombination

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The long-term objective of the research proposed here is to understand the molecular mechanisms of homologous genetic recombination. These objectives are approached genetically by studying mutants altered in recombination and physically by analyzing DNA from cells undergoing recombination. The research is focused on meiotic recombination in the fission yeast Schizosaccharomyces pombe, a widely studied model organism with molecular similarities to multicellular eukaryotes, including humans. Specific aims of the research are to 1) determine the genetic regulation of meiotic DNA breakage and repair during meiosis, 2) isolate and analyze new 5. pombe mutants altered in the early and late steps of recombination, and 3) elucidate the mechanism of a novel pathway of meiotic recombination active in the apparent absence of DNA double-strand breaks. Recombination is important for generating diversity at both the organismal and cellular levels, for proper segregation of chromosomes during meiosis, and for repair of DNA double-strand breaks. Aberrancies of recombination generate chromosomal rearrangements, such as translocations, duplications, and deficiencies. These rearrangements are associated with, and in some cases are the cause of, birth defects and cancers. Understanding the molecular mechanism of recombination is important in determining the causes of these diseases and possibly preventing them.