One of the unique features of eukaryotes is the ability to go through meiosis, a specialized division that yields gametes for sexual reproduction. The ability to enter meiosis is precisely regulated: it is generally restricted to particular tissues, types of cells, or environments. The objective of this proposal is to determine the mechanism by which cells of the yeast Saccharomyces cerevisiae decide to enter meiosis. The signals that activate meiosis, starvation in the absence of glucose and the determinants of a/alpha cell type, converge to stimulate expression of the IME1 gene. The IME1 product (Ime1p) then stimulates expression of the large set of early meiotic genes which are required for more specific meiotic events. Ime1p is not homologous to other proteins of known function, but has a novel tyrosine-rich transcriptional activation domain. Prior studies have identified three gene products that are required for Ime1p to activate early meiotic genes: Rim11p, Rim15p, and Ume6p. Rim11p is a constitutively-expressed protein kinase that phosphorylates Ime1p. Rim15p is a glucose-repressible protein kinase. Ume6p is a constitutively-expressed DNA binding protein that functions as a repressor in the absence of Ime1p, and as a transcriptional activator in the presence of Ime1p. Dr. Mitchell seeks to test the hypothesis that phosphorylation by Rim11p permits Ime1p to convert Ume6p to an activator through regulated physical interaction.
The specific aims are to determine the requirements for Ime1p-Ume6p interaction and function, to determine how nitrogen starvation and meiotic DNA synthesis stimulate the Ime1p-dependent activation pathway, and to determine how Ime1p, Rim11p, and Ume6p exert effects on different classes of target genes.
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