Multisite Phosphorylation of the Sum1 Transcriptional Repressor by S-Phase Kinases Controls Exit from Meiotic Prophase in Yeast.

Authors

Daniel Corbi, Department of Biochemistry and Molecular Biology, Thomas Jefferson University
Sham Sunder, Department of Biochemistry and Molecular Biology, Thomas Jefferson University
Michael Weinreich, Laboratory of Genome Integrity and Tumorigenesis, Van Andel Research Institute
Aikaterini Skokotas, Rosemont College
Erica S Johnson, Department of Biochemistry and Molecular Biology, Thomas Jefferson UniversityFollow
Edward Winter, Department of Biochemistry and Molecular Biology, Thomas Jefferson UniversityFollow

Document Type

Article

Publication Date

6-15-2014

Comments

This article has been peer reviewed. It was published in: Molecular and Cellular Biology.

Volume 34, Issue 12, June 2014, Pages 2249-2263.

The published version is available at http://mcb.asm.org/content/34/12/2249.long.

Copyright © 2014, American Society for Microbiology.

Abstract

Activation of the meiotic transcription factor Ndt80 is a key regulatory transition in the life cycle of Saccharomyces cerevisiae because it triggers exit from pachytene and entry into meiosis. The NDT80 promoter is held inactive by a complex containing the DNA-binding protein Sum1 and the histone deacetylase Hst1. Meiosis-specific phosphorylation of Sum1 by the protein kinases Cdk1, Ime2, and Cdc7 is required for NDT80 expression. Here, we show that the S-phase-promoting cyclin Clb5 activates Cdk1 to phosphorylate most, and perhaps all, of the 11 minimal cyclin-dependent kinase (CDK) phospho-consensus sites (S/T-P) in Sum1. Nine of these sites can individually promote modest levels of meiosis, yet these sites function in a quasiadditive manner to promote substantial levels of meiosis. Two Cdk1 sites and an Ime2 site individually promote high levels of meiosis, likely by preparing Sum1 for phosphorylation by Cdc7. Chromatin immunoprecipitation reveals that the phosphorylation sites are required for removal of Sum1 from the NDT80 promoter. We also find that Sum1, but not its partner protein Hst1, is required to repress NDT80 transcription. Thus, while the phosphorylation of Sum1 may lead to dissociation from DNA by influencing Hst1, it is the presence of Sum1 on DNA that determines whether NDT80 will be expressed.

Recommended Citation

Corbi, Daniel; Sunder, Sham; Weinreich, Michael; Skokotas, Aikaterini; Johnson, Erica S; and Winter, Edward, "Multisite Phosphorylation of the Sum1 Transcriptional Repressor by S-Phase Kinases Controls Exit from Meiotic Prophase in Yeast." (2014). Department of Biochemistry and Molecular Biology Faculty Papers. Paper 79.
https://jdc.jefferson.edu/bmpfp/79

PubMed ID

24710277