One of the unique features of eukaryotic organisms is the ability to go through meiosis, the process that yields gametes for sexual reproduction. Meiosis is precisely regulated: meiosis is generally restricted to particular tissues, types of cells, or environments. The object of this proposal is to understand how cells of the yeast, Saccharomyces cerevisiae, exit the mitotic cycle and enter meiosis. This decision is determined both by the mating type locus (MAT) and by nutritional signals. Meiosis is restricted to a particular type of cell, the a/alpha cell, that expresses the two MAT alleles, MATa and MATalpha. a/alpha cells enter meiosis only in response to nutritional limitation. The RME1 gene (regulator of meiosis) encodes an inhibitor of meiosis. RME1 is transcriptionally repressed by the combination of one MATa product and one MAT alpha product. Accordingly, repression of RME1 permits a/alpha cells to enter meiosis in response to starvation. The main question now is the mechanism through which RME1 product inhibits meiosis. The answer has three parts: when, in meiosis, RME1 product acts, what the target genes are whose expression or products are inhibited by RME1 protein, and how RME1 protein interacts with its targets to exert inhibition. Present studies address features of the RME1 protein, such as primary sequence, biochemical activities, and subcellular localization. This information will provide clues about RME1 product activity.
The specific aims of this proposal are to identify the meiotic events and target genes that are inbitited by RME1 product, to determine how target gene activity is regulated, and to determine the mechanism through which RME1 product governs target gene activity. These studies will be accomplished through approaches of molecular and classical genetics. This work will elucidate the regulation of a fundamental biological process at the molecular level.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
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Microbial Physiology and Genetics Subcommittee 2 (MBC)
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Columbia University (N.Y.)
Schools of Medicine
New York
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Subramanian, Shoba; Woolford, Carol A; Desai, Jigar V et al. (2012) cis- and trans-acting localization determinants of pH response regulator Rim13 in Saccharomyces cerevisiae. Eukaryot Cell 11:1201-9
Morohashi, Nobuyuki; Nakajima, Kumiko; Kurihara, Daichi et al. (2007) A nucleosome positioned by alpha2/Mcm1 prevents Hap1 activator binding in vivo. Biochem Biophys Res Commun 364:583-8
Boysen, Jacob H; Mitchell, Aaron P (2006) Control of Bro1-domain protein Rim20 localization by external pH, ESCRT machinery, and the Saccharomyces cerevisiae Rim101 pathway. Mol Biol Cell 17:1344-53
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Mitchell, Aaron P (2003) Updated view of Cryptococcus neoformans mating type and virulence. Infect Immun 71:4829-30
Lamb, Teresa M; Mitchell, Aaron P (2003) The transcription factor Rim101p governs ion tolerance and cell differentiation by direct repression of the regulatory genes NRG1 and SMP1 in Saccharomyces cerevisiae. Mol Cell Biol 23:677-86
Shimizu, Mitsuhiro; Takahashi, Keiko; Lamb, Teresa M et al. (2003) Yeast Ume6p repressor permits activator binding but restricts TBP binding at the HOP1 promoter. Nucleic Acids Res 31:3033-7
Blumental-Perry, Anna; Li, Weishi; Simchen, Giora et al. (2002) Repression and activation domains of RME1p structurally overlap, but differ in genetic requirements. Mol Biol Cell 13:1709-21

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