The objective of the proposed research is to use yeast as a genetically tractable model to elucidate molecular mechanisms of cell cycle control. Specifically genetic strategies will be employed (1) to determine how cyclin-dependent kinases effect cell cycle transitions, (2) to analyze the regulation of cell morphogenesis and (3) DNA replication, (4) to elucidate molecular mechanisms of cell cycle checkpoints and (5) to determine the molecular basis for hormonal control of the cell cycle. The primary approach to be employed is to identify important loci by mutational analysis, clone the relevant wild-type genes and then to analyze the encoded products at the molecular level. In other experiments, the products of known loci will be tested for interaction both genetically and physically. The importance of this work to health issues lies in the high degree of conservation between yeast and human cells on matters pertinent to cell division and cell proliferation. It is likely that advances made through the unique ability to manipulate yeast genetically will have an impact on understanding of human diseases of cell proliferation such as cancer and ultimately on therapeutic approaches.
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