MOLECULAR MECHANISMS OF GENETIC RECOMBINATION

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The long-term objection of the research proposed here is to understand the molecular mechanisms of homologous recombination and of base-mismatch repair in DNA, and the mechanisms that control these processes. These objectives are approached biochemically by studying the enzymes promoting recombination and repair, and genetically by studying mutant organisms altered in these processes. The research is focused on the RecBCD pathway of recombination in Escherichia coli, meiotic recombination in schizosaccharomyces pombe, and mismatch repair in S. Pombe. Specific aims of the research in E. coli are to 1) determine the physical change of RecBCD enzyme at Chi sites, and 2) elucidate the mechanism of DNA unwinding by RecBCD enzyme. Specific aims of the research in S. pombe are to 1) analyze meiotic recombination-deficient (rec) mutants, the re genes and their products, 2) search for recombination intermediates, using a physical assay, and determine the rec gene requirements for their formation, and 3) determine the roles of exonuclease I and additional components in mismatch repair. Recombination is important for generating diversity at both the organismal and cellular levels. Aberrancies of recombination generate chromosomal rearrangements, such as deletions and translocations. Chromosomal rearrangements are associated with, and may be a 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. Mismatch repair-deficiencies are associated with several types of cancer. Identifying the components of mismatch repair may lead to early diagnosis and prevention of cancer.