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Differential susceptibility of yeast S and M phase CDK complexes to inhibitory tyrosine phosphorylation.

Publication ,  Journal Article
Keaton, MA; Bardes, ESG; Marquitz, AR; Freel, CD; Zyla, TR; Rudolph, J; Lew, DJ
Published in: Curr Biol
July 17, 2007

BACKGROUND: Several checkpoint pathways employ Wee1-mediated inhibitory tyrosine phosphorylation of cyclin-dependent kinases (CDKs) to restrain cell-cycle progression. Whereas in vertebrates this strategy can delay both DNA replication and mitosis, in yeast cells only mitosis is delayed. This is particularly surprising because yeasts, unlike vertebrates, employ a single family of cyclins (B type) and the same CDK to promote both S phase and mitosis. The G2-specific arrest could be explained in two fundamentally different ways: tyrosine phosphorylation of cyclin/CDK complexes could leave sufficient residual activity to promote S phase, or S phase-promoting cyclin/CDK complexes could somehow be protected from checkpoint-induced tyrosine phosphorylation. RESULTS: We demonstrate that in Saccharomyces cerevisiae, several cyclin/CDK complexes are protected from inhibitory tyrosine phosphorylation, allowing Clb5,6p to promote DNA replication and Clb3,4p to promote spindle assembly, even under checkpoint-inducing conditions that block nuclear division. In vivo, S phase-promoting Clb5p/Cdc28p complexes were phosphorylated more slowly and dephosphorylated more effectively than were mitosis-promoting Clb2p/Cdc28p complexes. Moreover, we show that the CDK inhibitor (CKI) Sic1p protects bound Clb5p/Cdc28p complexes from tyrosine phosphorylation, allowing the accumulation of unphosphorylated complexes that are unleashed when Sic1p is degraded to promote S phase. The vertebrate CKI p27(Kip1) similarly protects Cyclin A/Cdk2 complexes from Wee1, suggesting that the antagonism between CKIs and Wee1 is evolutionarily conserved. CONCLUSIONS: In yeast cells, the combination of CKI binding and preferential phosphorylation/dephosphorylation of different B cyclin/CDK complexes renders S phase progression immune from checkpoints acting via CDK tyrosine phosphorylation.

Duke Scholars

Published In

Curr Biol

DOI

ISSN

0960-9822

Publication Date

July 17, 2007

Volume

17

Issue

14

Start / End Page

1181 / 1189

Location

England

Related Subject Headings

  • ras-GRF1
  • Tyrosine
  • Thiazolidines
  • Spindle Apparatus
  • Saccharomyces cerevisiae Proteins
  • Saccharomyces cerevisiae
  • S Phase
  • Protein-Tyrosine Kinases
  • Protein Tyrosine Phosphatases
  • Phosphorylation
 

Citation

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MLA
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Keaton, M. A., Bardes, E. S. G., Marquitz, A. R., Freel, C. D., Zyla, T. R., Rudolph, J., & Lew, D. J. (2007). Differential susceptibility of yeast S and M phase CDK complexes to inhibitory tyrosine phosphorylation. Curr Biol, 17(14), 1181–1189. https://doi.org/10.1016/j.cub.2007.05.075
Keaton, Mignon A., Elaine S. G. Bardes, Aron R. Marquitz, Christopher D. Freel, Trevin R. Zyla, Johannes Rudolph, and Daniel J. Lew. “Differential susceptibility of yeast S and M phase CDK complexes to inhibitory tyrosine phosphorylation.Curr Biol 17, no. 14 (July 17, 2007): 1181–89. https://doi.org/10.1016/j.cub.2007.05.075.
Keaton MA, Bardes ESG, Marquitz AR, Freel CD, Zyla TR, Rudolph J, et al. Differential susceptibility of yeast S and M phase CDK complexes to inhibitory tyrosine phosphorylation. Curr Biol. 2007 Jul 17;17(14):1181–9.
Keaton, Mignon A., et al. “Differential susceptibility of yeast S and M phase CDK complexes to inhibitory tyrosine phosphorylation.Curr Biol, vol. 17, no. 14, July 2007, pp. 1181–89. Pubmed, doi:10.1016/j.cub.2007.05.075.
Keaton MA, Bardes ESG, Marquitz AR, Freel CD, Zyla TR, Rudolph J, Lew DJ. Differential susceptibility of yeast S and M phase CDK complexes to inhibitory tyrosine phosphorylation. Curr Biol. 2007 Jul 17;17(14):1181–1189.
Journal cover image

Published In

Curr Biol

DOI

ISSN

0960-9822

Publication Date

July 17, 2007

Volume

17

Issue

14

Start / End Page

1181 / 1189

Location

England

Related Subject Headings

  • ras-GRF1
  • Tyrosine
  • Thiazolidines
  • Spindle Apparatus
  • Saccharomyces cerevisiae Proteins
  • Saccharomyces cerevisiae
  • S Phase
  • Protein-Tyrosine Kinases
  • Protein Tyrosine Phosphatases
  • Phosphorylation