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A MAP kinase-dependent actin checkpoint ensures proper spindle orientation in fission yeast

Nature volume 412, pages 352–355 (2001)Cite this article

Abstract

The accurate segregation of chromosomes at mitosis depends on a correctly assembled bipolar spindle that exerts balanced forces on each sister chromatid1,2. The integrity of mitotic chromosome segregation is ensured by the spindle assembly checkpoint (SAC) that delays mitosis in response to defective spindle organisation or failure of chromosome attachment2,3. Here we describe a distinct mitotic checkpoint in the fission yeast, Schizosaccharomyces pombe, that monitors the integrity of the actin cytoskeleton and delays sister chromatid separation, spindle elongation and cytokinesis until spindle poles have been properly oriented. This mitotic delay is imposed by a stress-activated mitogen-activated protein (MAP) kinase pathway but is independent of the anaphase-promoting complex (APC)4,5.

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Figure 1: Latrunculin B induces a mitotic delay.
Figure 2: Mitotic actin checkpoint delays the separation of sister chromatids.
Figure 3: The mitotic actin checkpoint is independent of the SAC and the APC.
Figure 4: The mitotic actin checkpoint is dependent on the stress-activated Sty1 MAP kinase pathway.

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References

  1. Nicklas, R. B. How cells get the right chromosomes. Science 275, 632–637 (1997).

    CAS  PubMed  Google Scholar 

  2. Amon, A. The spindle checkpoint. Curr. Opin. Genet. Dev. 9, 69–75 (1999).

    CAS  PubMed  Google Scholar 

  3. Hardwick, K. G. et al. Lesions in many different spindle components activate the spindle checkpoint in the budding yeast Saccharomyces cerevisiae. Genetics 152, 509–518 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  4. Zachariae, W. & Nasmyth, K. Whose end is destruction: cell division and the anaphase-promoting complex. Genes Dev. 13, 2039–2058 (1999).

    CAS  PubMed  Google Scholar 

  5. Yanagida, M. et al. Control of metaphase-anaphase progression by proteolysis: cyclosome function regulated by the protein kinase A pathway, ubiquitination and localization. Phil. Trans. R. Soc. Lond. B 354, 1559–1569 (1999).

    CAS  Google Scholar 

  6. Marks, J. M. & Hyams, J. S. Localisation of F actin through the cell division cycle of Schizosaccharomyces pombe. Eur. J. Cell Biol. 39, 27–32 (1985).

    Google Scholar 

  7. Spector, I., Shochet, N. R., Kashman, Y. & Groweiss, A. Latrunculins: novel marine toxins that disrupt microfilament organization in cultured cells. Science 219, 493–495 (1983).

    ADS  CAS  PubMed  Google Scholar 

  8. Hagan, I. M. & Hyams, J. S. Forces acting on the fission yeast anaphase spindle. Cell. Motil. Cytoskeleton 34, 69–75 (1996).

    CAS  PubMed  Google Scholar 

  9. Mallavarapu, A., Sawin, K. & Mitchison, T. A switch in microtubule dynamics at the onset of anaphase B in the mitotic spindle of Schizosaccharomyces pombe. Curr. Biol. 9, 1423–1426 (1999).

    CAS  PubMed  Google Scholar 

  10. Nabeshima, K. et al. Dynamics of centromeres during metaphase-anaphase transition in fission yeast: Dis1 is implicated in force balance in metaphase bipolar spindle. Mol. Biol. Cell 9, 3211–3225 (1998).

    CAS  PubMed  PubMed Central  Google Scholar 

  11. Ishiguro, J. & Kobayashi, W. An actin point-mutation neighboring the ‘hydrophobic plug’ causes defects in the maintenance of cell polarity and septum organization in the fission yeast Schizosaccharomyces pombe. FEBS Lett. 392, 237–241 (1996).

    CAS  PubMed  Google Scholar 

  12. Birkenbihl, R. P. & Subramani, S. The rad21 gene product of Schizosaccharomyces pombe is a nuclear, cell cycle-regulated phosphoprotein. J. Biol. Chem. 270, 7703–7711 (1995).

    CAS  PubMed  Google Scholar 

  13. Tomonaga, T. et al. Characterization of fission yeast cohesin: essential anaphase proteolysis of Rad21 phosphorylated in the S phase. Genes Dev. 14, 2757–2770 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  14. Chen, R. H., Waters, J. C., Salmon, E. D. & Murray, A. W. Association of spindle assembly checkpoint component XMAD2 with unattached kinetochores. Science 274, 242–246 (1996).

    ADS  CAS  PubMed  Google Scholar 

  15. He, X., Patterson, T. E. & Sazer, S. The Schizosaccharomyces pombe spindle checkpoint protein Mad2p blocks anaphase and genetically interacts with the anaphase-promoting complex. Proc. Natl Acad. Sci. USA 94, 7965–7970 (1997).

    ADS  CAS  PubMed  PubMed Central  Google Scholar 

  16. Funabiki, H. et al. Cut2 proteolysis required for sister-chromatid separation in fission yeast. Nature 381, 438–441 (1996).

    ADS  CAS  PubMed  Google Scholar 

  17. Uhlmann, F. et al. Cleavage of cohesin by the CD clan protease separin triggers anaphase in yeast. Cell 103, 375–386 (2000).

    CAS  PubMed  Google Scholar 

  18. Moreno, S., Hayles, J. & Nurse, P. Regulation of p34cdc2 protein kinase during mitosis. Cell 58, 361–372 (1989).

    CAS  PubMed  Google Scholar 

  19. Alfa, C. E., Ducommun, B., Beach, D. & Hyams, J. S. Distinct nuclear and spindle pole body population of cyclin-cdc2 in fission yeast. Nature 347, 680–682 (1990).

    ADS  CAS  PubMed  Google Scholar 

  20. Shiozaki, K. & Russell, P. Conjugation, meiosis, and the osmotic stress response are regulated by Spc1 kinase through Atf1 transcription factor in fission yeast. Genes Dev. 10, 2276–2288 (1996).

    CAS  PubMed  Google Scholar 

  21. Wilkinson, M. G. et al. The Atf1 transcription factor is a target for the Sty1 stress activated MAP kinase pathway in fission yeast. Genes Dev. 10, 2289–2301 (1996).

    CAS  PubMed  Google Scholar 

  22. Millar, J. B. A., Buck, V. & Wilkinson, M. G. Pyp1 and Pyp2 PTPases dephosphorylate an osmosensing MAP kinase controlling cell size at division in fission yeast. Genes Dev. 9, 2117–2130 (1995).

    CAS  PubMed  Google Scholar 

  23. Shiozaki, K. & Russell, P. Cell cycle control linked to extracellular environment by MAP kinase pathway in fission yeast. Nature 378, 739–743 (1995).

    ADS  CAS  PubMed  Google Scholar 

  24. Ohkura, H., Hagan, I. M. & Glover, D. M. The conserved Schizosaccharomyces pombe kinase plo1, required to form a bipolar spindle, the actin ring, and septum, can drive septum formation in G1 and G2 cells. Genes Dev. 9, 1059–1073 (1995).

    CAS  PubMed  Google Scholar 

  25. Tanaka, K. et al. The role of Plo1 kinase in mitotic commitment and septation in Schizosaccharomyces pombe. EMBO J. 20, 1259–1270 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  26. Knoblich, J. A. Mechanisms of asymmetric cell division during animal development. Curr. Opin. Cell Biol. 9, 833–841 (1997).

    CAS  PubMed  Google Scholar 

  27. Lu, B., Jan, L. Y. & Jan, Y. N. Asymmetric cell division: lessons from flies and worms. Curr. Opin. Genet. Dev. 8, 392–399 (1998).

    CAS  PubMed  Google Scholar 

  28. Yamashita, M., Yoshikuni, M., Hirai, T., Fukada, S. & Nagahama, Y. A monoclonal antibody against the PSTAIR sequence of p34cdc2 catalytic subunit of maturation-promoting factor and key regulator of the cell cycle. Dev. Growth Differ. 33, 617–624 (1991).

    CAS  Google Scholar 

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Acknowledgements

We thank V. Amin and K. Adams for technical assistance; F. Uhlmann and K. Nasmyth for communicating results before publication; and T. Matsumoto, S. Subramani and M. Yanagida for strains and reagents. We also thank V. Buck, L. Johnston, S. Jensen and D. Mulhivill for comments and critical reading of the manuscript, and members of the Hyams and Millar laboratories for their encouragement and support. This work was supported by a Wellcome Trust grant to J.S.H. and by a MRC grant to J.B.A.M.

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Author notes

  1. Yannick Gachet, Sylvie Tournier and Jonathan B. A. Millar: These authors contributed equally to this work

Authors and Affiliations

  1. Department of Biology, University College London, Gower Street, London, WC1E 6B, UK

    Yannick Gachet & Jeremy S. Hyams

  2. Division of Yeast Genetics, National Institute for Medical Research, The Ridgeway, Mill Hill, London, NW7 1AA, UK

    Sylvie Tournier & Jonathan B. A. Millar

Authors
  1. Yannick Gachet
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  2. Sylvie Tournier
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  3. Jonathan B. A. Millar
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  4. Jeremy S. Hyams
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Corresponding author

Correspondence to Jonathan B. A. Millar.

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Gachet, Y., Tournier, S., Millar, J. et al. A MAP kinase-dependent actin checkpoint ensures proper spindle orientation in fission yeast. Nature 412, 352–355 (2001). https://doi.org/10.1038/35085604

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