The overall objective of our research program is to understand the genetic mechanisms that govern meiotic development. Our approach is to determine the structure, function, and regulation of selected meiosis-specific genes required for recombination and chromosome segregation, and to use these genes to uncover critical regulatory functions that specify the orderly progression of meiotic events. Of long-range interest is the relationship between meiotic and mitotic cell division controls, and the extent to which they interact. The unicellular eucaryote, Saccharomyces cerevisiae, is utilized as a model system.
The specific aims emphasize: 1) the functions of prototype meiosis-specific SPO (sporulation-defective) genes in controlling exchange and segregation, 2) the mechanism by which UME (unscheduled meiotic expression) loci, repress these genes during mitotic division and govern their time of expression during meiosis, 3) the genetic basis of return-to-growth and irreversible commitment to meiosis, and their roles in the overall coordination of meiotic events, and, 4) identification and isolation of new positive and negative regulators controlling the progression of meiotic events. Overexpressed cloned SPO and UME genes and new mutant alleles will be examined phenotypically to test specific models of their function. The synthesis and stability of their meiosis-specific transcripts and protein products will be determined during mitosis and meiosis. The interactions of the altered genes with other genes required for meiotic development and known CDC (cell division cycle) genes will be assayed by epistasis and suppressor analysis. Meiosis plays a central role in the sexual reproduction of nearly all eukaryotes. The major genetic events that occur during its two cell divisions are critical for generating genetic diversity and producing offspring with normal chromosome numbers. Our studies should help uncover the strategies used to coordinate a complex series of events affecting chromosome behavior into a successful developmental pathway. Analysis of the mechanisms that govern cell division and differentiation, and the factors essential for exchange and segregation should also contribute significantly to understanding the basis of malignancy and of diseases associated with instability and abnormal chromosome transmission.
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