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PMID: 20403323 Published · ppublish English Journal Article Research Support, N.I.H., Extramural

Periodic cyclin-Cdk activity entrains an autonomous Cdc14 release oscillator.

Cell ·Vol. 141 ·No. 2 ·2010-04-16 ·Pages 268-79

Lu Y, Cross FR

Abstract

One oscillation of Cyclin-dependent kinase (Cdk) activity, largely driven by periodic synthesis and destruction of cyclins, is tightly coupled to a single complete eukaryotic cell division cycle. Tight linkage of different steps in diverse cell-cycle processes to Cdk activity has been proposed to explain this coupling. Here, we demonstrate an intrinsically oscillatory module controlling nucleolar release and resequestration of the Cdc14 phosphatase, which is essential for mitotic exit in budding yeast. We find that this Cdc14 release oscillator functions at constant and physiological cyclin-Cdk levels, and is therefore independent of the Cdk oscillator. However, the frequency of the release oscillator is regulated by cyclin-Cdk activity. This observation together with its mechanism suggests that the intrinsically autonomous Cdc14 release cycles are locked at once-per-cell-cycle through entrainment by the Cdk oscillator in wild-type cells. This concept may have broad implications for the structure and evolution of eukaryotic cell-cycle control.

MeSH Terms
Cdh1 Proteins Cell Cycle Proteins/metabolism Cell Nucleolus/metabolism Cyclin B/metabolism Cyclins/metabolism Mitosis Models, Biological Protein Kinases/metabolism Protein Serine-Threonine Kinases Protein Tyrosine Phosphatases/metabolism Saccharomyces cerevisiae/cytology,metabolism Saccharomyces cerevisiae Proteins/metabolism
Chemicals
CDC14 protein, S cerevisiae CLB2 protein, S cerevisiae Cdh1 Proteins Cell Cycle Proteins Cyclin B Cyclins Saccharomyces cerevisiae Proteins Protein Kinases Protein Serine-Threonine Kinases CDC5 protein, S cerevisiae Protein Tyrosine Phosphatases
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Lu Ying
The Rockefeller University, 1230 York Avenue, New York, New York 10065, USA.
Cross Frederick R
References (59)
59 references, click to expand
  1. Downregulation of PP2A(Cdc55) phosphatase by separase initiates mitotic exit in budding yeast.
    Cell. 2006 May 19;125(4):719-32 PMID: 16713564
  2. Phosphorylation by cyclin B-Cdk underlies release of mitotic exit activator Cdc14 from the nucleolus.
    Science. 2004 Jul 23;305(5683):516-9 PMID: 15273393
  3. Cfi1 prevents premature exit from mitosis by anchoring Cdc14 phosphatase in the nucleolus.
    Nature. 1999 Apr 29;398(6730):818-23 PMID: 10235265
  4. Exit from mitosis in budding yeast: biphasic inactivation of the Cdc28-Clb2 mitotic kinase and the role of Cdc20.
    Mol Cell. 2000 Mar;5(3):501-11 PMID: 10882135
  5. A microfluidic device for temporally controlled gene expression and long-term fluorescent imaging in unperturbed dividing yeast cells.
    PLoS One. 2008 Jan 23;3(1):e1468 PMID: 18213377
  6. A Bub2p-dependent spindle checkpoint pathway regulates the Dbf2p kinase in budding yeast.
    EMBO J. 1999 May 4;18(9):2424-34 PMID: 10228157
  7. G1-specific cyclins of S. cerevisiae: cell cycle periodicity, regulation by mating pheromone, and association with the p34CDC28 protein kinase.
    Cell. 1990 Jul 27;62(2):225-37 PMID: 2142620
  8. On the Origin of Species by Means of Natural Selection, or the Preservation of Favoured Races in the Struggle for Life.
    Br Foreign Med Chir Rev. 1860 Apr;25(50):367-404 PMID: 30164232
  9. Orchestrating anaphase and mitotic exit: separase cleavage and localization of Slk19.
    Nat Cell Biol. 2001 Sep;3(9):771-7 PMID: 11533655
  10. The role of the polo kinase Cdc5 in controlling Cdc14 localization.
    Mol Biol Cell. 2003 Nov;14(11):4486-98 PMID: 14551257
  11. Regulation of Cdc28 cyclin-dependent protein kinase activity during the cell cycle of the yeast Saccharomyces cerevisiae.
    Microbiol Mol Biol Rev. 1998 Dec;62(4):1191-243 PMID: 9841670
  12. Enigmatic variations: divergent modes of regulating eukaryotic DNA replication.
    Mol Cell. 2003 Nov;12(5):1067-75 PMID: 14636567
  13. Destruction of the CDC28/CLB mitotic kinase is not required for the metaphase to anaphase transition in budding yeast.
    EMBO J. 1993 May;12(5):1969-78 PMID: 8491189
  14. Mitotic exit in the absence of separase activity.
    Mol Biol Cell. 2009 Mar;20(5):1576-91 PMID: 19144818
  15. Phase locking induces scale-free topologies in networks of coupled oscillators.
    PLoS One. 2008 Jul 09;3(7):e2644 PMID: 18612423
  16. RNAi of mitotic cyclins in Drosophila uncouples the nuclear and centrosome cycle.
    Curr Biol. 2008 Feb 26;18(4):245-54 PMID: 18291653
  17. Separase, polo kinase, the kinetochore protein Slk19, and Spo12 function in a network that controls Cdc14 localization during early anaphase.
    Cell. 2002 Jan 25;108(2):207-20 PMID: 11832211
  18. A mechanism for coupling exit from mitosis to partitioning of the nucleus.
    Cell. 2000 Jul 7;102(1):21-31 PMID: 10929710
  19. Cdc14 activates cdc15 to promote mitotic exit in budding yeast.
    Curr Biol. 2000 May 18;10(10):615-8 PMID: 10837230
  20. Spatial regulation of the guanine nucleotide exchange factor Lte1 in Saccharomyces cerevisiae.
    J Cell Sci. 2002 Dec 15;115(Pt 24):4977-91 PMID: 12432084
  21. Coherence and timing of cell cycle start examined at single-cell resolution.
    Mol Cell. 2006 Jan 6;21(1):3-14 PMID: 16387649
  22. Cell cycle checkpoints: preventing an identity crisis.
    Science. 1996 Dec 6;274(5293):1664-72 PMID: 8939848
  23. Evidence that a free-running oscillator drives G1 events in the budding yeast cell cycle.
    Nature. 1999 Sep 23;401(6751):394-7 PMID: 10517640
  24. Domains, motifs, and scaffolds: the role of modular interactions in the evolution and wiring of cell signaling circuits.
    Annu Rev Biochem. 2006;75:655-80 PMID: 16756506
  25. Regulation of the localization of Dbf2 and mob1 during cell division of saccharomyces cerevisiae.
    Genes Genet Syst. 2001 Apr;76(2):141-7 PMID: 11434459
  26. Mitotic checkpoint genes in budding yeast and the dependence of mitosis on DNA replication and repair.
    Genes Dev. 1994 Mar 15;8(6):652-65 PMID: 7926756
  27. The phosphatase Cdc14 triggers mitotic exit by reversal of Cdk-dependent phosphorylation.
    Mol Cell. 1998 Dec;2(6):709-18 PMID: 9885559
  28. Saccharomyces cerevisiae cell cycle.
    Bacteriol Rev. 1974 Jun;38(2):164-98 PMID: 4599449
  29. The Swi5 transcription factor of Saccharomyces cerevisiae has a role in exit from mitosis through induction of the cdk-inhibitor Sic1 in telophase.
    Genetics. 1997 Jan;145(1):85-96 PMID: 9017392
  30. The Bub2p spindle checkpoint links nuclear migration with mitotic exit.
    Mol Cell. 2000 Jul;6(1):1-10 PMID: 10949022
  31. The Polo-related kinase Cdc5 activates and is destroyed by the mitotic cyclin destruction machinery in S. cerevisiae.
    Curr Biol. 1998 Apr 23;8(9):497-507 PMID: 9560342
  32. Yeast Hct1 is a regulator of Clb2 cyclin proteolysis.
    Cell. 1997 Aug 22;90(4):683-93 PMID: 9288748
  33. Exit from mitosis is triggered by Tem1-dependent release of the protein phosphatase Cdc14 from nucleolar RENT complex.
    Cell. 1999 Apr 16;97(2):233-44 PMID: 10219244
  34. Destabilized green fluorescent protein for monitoring dynamic changes in yeast gene expression with flow cytometry.
    Yeast. 2000 Oct;16(14):1313-23 PMID: 11015728
  35. Closing mitosis: the functions of the Cdc14 phosphatase and its regulation.
    Annu Rev Genet. 2004;38:203-32 PMID: 15568976
  36. Biological rhythms and the behavior of populations of coupled oscillators.
    J Theor Biol. 1967 Jul;16(1):15-42 PMID: 6035757
  37. Evolution of eukaryotic cell cycle regulation: stepwise addition of regulatory kinases and late advent of the CDKs.
    Curr Biol. 2003 Jan 21;13(2):173-7 PMID: 12546794
  38. Analysis of the mitotic exit control system using locked levels of stable mitotic cyclin.
    Mol Syst Biol. 2009;5:328 PMID: 19920813
  39. From molecular to modular cell biology.
    Nature. 1999 Dec 2;402(6761 Suppl):C47-52 PMID: 10591225
  40. Characterization of four B-type cyclin genes of the budding yeast Saccharomyces cerevisiae.
    Mol Biol Cell. 1992 Jul;3(7):805-18 PMID: 1387566
  41. Centrosome duplication continues in cycloheximide-treated Xenopus blastulae in the absence of a detectable cell cycle.
    J Cell Biol. 1990 Jun;110(6):2033-42 PMID: 2190990
  42. The KEN box: an APC recognition signal distinct from the D box targeted by Cdh1.
    Genes Dev. 2000 Mar 15;14(6):655-65 PMID: 10733526
  43. Global control of cell-cycle transcription by coupled CDK and network oscillators.
    Nature. 2008 Jun 12;453(7197):944-7 PMID: 18463633
  44. Sister chromatid separation and chromosome re-duplication are regulated by different mechanisms in response to spindle damage.
    EMBO J. 1999 May 17;18(10):2707-21 PMID: 10329618
  45. A quantitative model for the cdc2 control of S phase and mitosis in fission yeast.
    Trends Genet. 1996 Sep;12(9):345-50 PMID: 8855663
  46. Phosphorylation of Sic1p by G1 Cdk required for its degradation and entry into S phase.
    Science. 1997 Oct 17;278(5337):455-60 PMID: 9334303
  47. At the heart of the budding yeast cell cycle.
    Trends Genet. 1996 Oct;12(10):405-12 PMID: 8909137
  48. Protein synthesis and the cell cycle: centrosome reproduction in sea urchin eggs is not under translational control.
    J Cell Biol. 1990 Jun;110(6):2025-32 PMID: 2351692
  49. The Polo-like kinase Cdc5p and the WD-repeat protein Cdc20p/fizzy are regulators and substrates of the anaphase promoting complex in Saccharomyces cerevisiae.
    EMBO J. 1998 Mar 2;17(5):1336-49 PMID: 9482731
  50. The effects of molecular noise and size control on variability in the budding yeast cell cycle.
    Nature. 2007 Aug 23;448(7156):947-51 PMID: 17713537
  51. CDC20 and CDH1: a family of substrate-specific activators of APC-dependent proteolysis.
    Science. 1997 Oct 17;278(5337):460-3 PMID: 9334304
  52. Multi-step control of spindle pole body duplication by cyclin-dependent kinase.
    Nat Cell Biol. 2001 Jan;3(1):38-42 PMID: 11146624
  53. Evolution of the cell cycle.
    Philos Trans R Soc Lond B Biol Sci. 1995 Sep 29;349(1329):271-81 PMID: 8577838
  54. APC-dependent proteolysis of the mitotic cyclin Clb2 is essential for mitotic exit.
    Nature. 2002 Aug 1;418(6897):556-62 PMID: 12152084
  55. Multiple levels of cyclin specificity in cell-cycle control.
    Nat Rev Mol Cell Biol. 2007 Feb;8(2):149-60 PMID: 17245415
  56. Cell cycle-dependent transcription in yeast: promoters, transcription factors, and transcriptomes.
    Oncogene. 2005 Apr 18;24(17):2746-55 PMID: 15838511
  57. Synchronization and rhythmic processes in physiology.
    Nature. 2001 Mar 8;410(6825):277-84 PMID: 11258383
  58. Phosphorylation and spindle pole body localization of the Cdc15p mitotic regulatory protein kinase in budding yeast.
    Curr Biol. 2000 Mar 23;10(6):329-32 PMID: 10744974
  59. APC/C-Cdh1-mediated degradation of the Polo kinase Cdc5 promotes the return of Cdc14 into the nucleolus.
    Genes Dev. 2008 Jan 1;22(1):79-90 PMID: 18172166
Article Info
Journal
Cell
Abbr.
Cell
ISSN
1097-4172
DOI
10.1016/j.cell.2010.03.021
Published
2010-04-16
Pages
268-79
Language
English
Region
United States
NLM ID
0413066
PMCID
PMC4549071
Subset
IM
Grants
NIGMS NIH HHS · R01 GM047238 · United States
NIGMS NIH HHS · R01 GM078153 · United States
NIGMS NIH HHS · GM47238 · United States
NIGMS NIH HHS · GM078153 · United States
Corrections
CommentIn
PMID: 20403319
External Links
PubMed source DOI: 10.1016/j.cell.2010.03.021 PMC Full Text View journal details
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