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.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
2R01GM039531-10
Application #
2022198
Study Section
Special Emphasis Panel (ZRG5-EVR (01))
Project Start
1988-02-03
Project End
2001-01-31
Budget Start
1997-02-01
Budget End
1998-01-31
Support Year
10
Fiscal Year
1997
Total Cost
Indirect Cost
Name
Columbia University (N.Y.)
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
167204994
City
New York
State
NY
Country
United States
Zip Code
10032
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
Morohashi, Nobuyuki; Yamamoto, Yuichi; Kuwana, Shunsuke et al. (2006) Effect of sequence-directed nucleosome disruption on cell-type-specific repression by alpha2/Mcm1 in the yeast genome. Eukaryot Cell 5:1925-33
Barwell, Karen J; Boysen, Jacob H; Xu, Wenjie et al. (2005) Relationship of DFG16 to the Rim101p pH response pathway in Saccharomyces cerevisiae and Candida albicans. Eukaryot Cell 4:890-9
Xu, Wenjie; Smith Jr, Frank J; Subaran, Ryan et al. (2004) Multivesicular body-ESCRT components function in pH response regulation in Saccharomyces cerevisiae and Candida albicans. Mol Biol Cell 15:5528-37
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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