MEIOTIC INTERACTIONS OF THE RECA HOMOLOGUE DMCL

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Homologous recombination is required during meiosis to promote accurate segregation of homologous chromosomes at the first meiotic division. Several proteins have been identified that are required for MEIOTIC RECOMBINATION in the yeast Saccharomyces, but the specific role of these proteins in recombination is largely unknown. The long term goals of this work are to determine the molecular mechanism of meiotic recombination and the way in which meiotic cells ensure that recombination is complete before undergoing division. This study focuses on one meiotic protein, Dmc1, that is required for meiotic recombination. Thy homology of Dmc1 to the E. coli RecA protein suggests Dmc1 plays a pivotal role in recombination. RecA is required for recombination and REPAIR OF DNA DAMAGE in E. coli. Purified RecA promotes the central reaction in recombination: the formation of homologous joints between two DNA molecules. Dmc1 protein will be purified and characterized to determine what activities it shares with RecA. The formation of recombination products requires numerous enzymatic activities in addition to those displayed by RecA. Some or all of the proteins required for meiotic recombination may form a multiprotein complex. There is existing cytological evidence that large complexes form during meiotic recombination. In addition, two recombination proteins that are related to Dmc1, have been shown to bind other recombination proteins. Fluorescence microscopy, immunoassay, and genetic selection will be used to identify proteins that form complexes with Dmc1 during recombination. Time-course and mutational analyses will be used to characterize the pathway of recombination complex assembly. Dmc1 also plays a role in the control of the meiotic CELL CYCLE. Mutants cells that lack Dmc1 arrest in meiosis. The mechanisms that causes cell cycle arrest in the absence of Dmc1 will be characterized genetically by isolation of genetic suppressor that fail to arrest. These experiments will yield results relevant to the etiology of birth defects and cancer and may also suggest ways to improve cancer therapy.