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 mutant organisms altered in recombination and biochemically by studying the enzymes promoting recombination and the reactions of DNA during recombination. The research is focused on meiotic recombination in the fission yeast Schizosaccharomyces pombe and on the RecBCD pathway of recombination in the bacterium Escherichia coli. Recombination in both of these situations is associated with the formation and repair of DNA double-strand breaks. Specific aims of the research in S. pombe are to 1) analyze meiotic DNA breaks and determine their role in recombination, 2) isolate and analyze S. pombe mutants altered in the late steps of recombination, and 3) assess the role of recombination in meiotic chromosome segregation. The specific aim of the research in E. coli is to elucidate the mechanism of DNA unwinding from a double-strand end by RecBCD enzyme, a traveling recombination machine. Recombination is important for generating diversity at both the organismal and cellular levels and for the repair of DNA double-strand breaks. Aberrancies of recombination generate chromosomal rearrangements, such as deletions, translocations, and deficiencies. These rearrangements are associated with, and may be a cause of, birth defects and cancers. Understanding the molecular mechanisms of recombination is important in determining the causes of these diseases and possibly preventing them.