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Molecular and Cellular Biology, January 2005, p. 440-450, Vol. 25, No. 1
0270-7306/05/$08.00+0     doi:10.1128/MCB.25.1.440-450.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Glucose Inhibits Meiotic DNA Replication through SCF^Grr1p-Dependent Destruction of Ime2p Kinase

Kedar Purnapatre, Misa Gray, Sarah Piccirillo, and Saul M. Honigberg^*

Division of Cell Biology and Biophysics, School of Biological Sciences, University of Missouri—Kansas City, Kansas City, Missouri

Received 17 August 2004/ Returned for modification 16 September 2004/ Accepted 27 September 2004

In the budding yeast Saccharomyces cerevisiae, the cell division cycle and sporulation are mutually exclusive cell fates; glucose, which stimulates the cell division cycle, is a potent inhibitor of sporulation. Addition of moderate concentrations of glucose (0.5%) to sporulation medium did not inhibit transcription of two key activators of sporulation, IME1 and IME2, but did increase levels of Sic1p, a cyclin-dependent kinase inhibitor, resulting in a block to meiotic DNA replication. The effects of glucose on Sic1p levels and DNA replication required Grr1p, a component of the SCF^Grr1p ubiquitin ligase. Sic1p is negatively regulated by Ime2p kinase, and several observations indicate that glucose inhibits meiotic DNA replication through SCF^Grr1p-mediated destruction of this kinase. First, Ime2p was destabilized in the presence of glucose, and this turnover required Grr1p, a second component of SCF^Grr1p, Cdc53p, and an SCF^Grr1p-associated E2 enzyme, Cdc34p. Second, Ime2p-ubiquitin conjugates were detected under conditions of rapid Ime2p turnover, and conjugation of Ime2p to ubiquitin required GRR1. Third, a mutant form of Ime2p (Ime2^PEST), in which a putative Grr1p-interacting sequence was deleted, was more stable than wild-type Ime2p. Finally, expression of the IME2^PEST allele bypassed the block to meiotic DNA replication caused by 0.5% glucose. In addition, Grr1p is required for later events in sporulation independently of its role in Ime2p turnover.

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* Corresponding author. Mailing address: Division of Cell Biology and Biophysics, University of Missouri—Kansas City, 5007 Rockhill Rd., Kansas City, MO 64110. Phone: (816) 235-2578. Fax: (816) 235-6553. E-mail: honigbergs{at}umkc.edu.

Present address: Ranbaxy Research Laboratories, Gurgaon 122001, Haryana, India.

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Molecular and Cellular Biology, January 2005, p. 440-450, Vol. 25, No. 1
0022-538X/05/$08.00+0     doi:10.1128/MCB.25.1.440-450.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

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