Abstract
Mitotic exit integrates the reversal of the phosphorylation events initiated by mitotic kinases with a controlled cytokinesis event that cleaves the cell in two. The mitotic exit network (MEN) of budding yeast regulates both processes, whereas the fission yeast equivalent, the septum initiation network (SIN), controls only the execution of cytokinesis. The components and architecture of the SIN and MEN are highly conserved1. At present, it is assumed that the functions of the core SIN–MEN components are restricted to their characterized roles at the end of mitosis. We now show that the NDR (nuclear Dbf2-related) kinase component of the fission yeast SIN, Sid2–Mob1, acts independently of the other known SIN components in G2 phase of the cell cycle to control the timing of mitotic commitment. Sid2–Mob1 promotes mitotic commitment by directly activating the NIMA (Never In Mitosis)-related kinase Fin1. Fin1’s activation promotes its own destruction, thereby making Fin1 activation a transient feature of G2 phase. This spike of Fin1 activation modulates the activity of the Pom1/Cdr1/Cdr2 geometry network towards Wee1.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$209.00 per year
only $17.42 per issue
Rent or buy this article
Prices vary by article type
from$1.95
to$39.95
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Simanis, V. Events at the end of mitosis in the budding and fission yeasts. J. Cell Sci. 116, 4263–4275 (2003).
Krien, M. et al. A NIMA homologue promotes chromatin condensation in fission yeast. J. Cell Sci. 111, 967–976 (1998).
Ye, X. S. et al. The NIMA protein kinase is hyperphosphorylated and activated downstream of p34cdc2/cyclin B: coordination of two mitosis promoting kinases. EMBO J. 14, 986–994 (1995).
Lehmann, A. & Toda, T. Fission yeast Skp1 is required for spindle morphology and nuclear membrane segregation at anaphase. FEBS Lett. 566, 77–82 (2004).
Mah, A. S. et al. Substrate specificity analysis of protein kinase complex Dbf2–Mob1 by peptide library and proteome array screening. BMC Biochem. 6 22, http://dx.doi.org/10.1186/1471-2091-6-22 (2005).
Chen, C. T. et al. The SIN kinase Sid2 regulates cytoplasmic retention of the S. pombe Cdc14-like phosphatase Clp1. Curr. Biol. 18, 1594–1599 (2008).
Meitinger, F. et al. Phosphorylation-dependent regulation of the F-BAR protein Hof1 during cytokinesis. Genes Dev. 25, 875–888 (2011).
Fantes, P. A. Isolation of cell-size mutants of a fission yeast by a new selective method—characterization of mutants and implications for division control mechanisms. J. Bacteriol. 146, 746–754 (1981).
Nurse, P. & Thuriaux, P. Regulatory genes-controlling mitosis in the fission yeast Schizosaccharomyces pombe. Genetics 96, 627–637 (1980).
Russell, P. & Nurse, P. Negative regulation of mitosis by wee1+, a gene encoding a protein-kinase homolog. Cell 49, 559–567 (1987).
Kanoh, J. & Russell, P. The protein kinase Cdr2, related to Nim1/Cdr1 mitotic inducer, regulates the onset of mitosis in fission yeast. Mol. Biol. Cell 9, 3321–3334 (1998).
Breeding, C. S. et al. The cdr2+ gene encodes a regulator of G(2)/M progression and cytokinesis in Schizosaccharomyces pombe. Mol. Biol. Cell 9, 3399–3415 (1998).
Martin, S. G. & Berthelot-Grosjean, M. Polar gradients of the DYRK-family kinase Pom1 couple cell length with the cell cycle. Nature 459, 852–856 (2009).
Moseley, J. B., Mayeux, A., Paoletti, A. & Nurse, P. A spatial gradient coordinates cell size and mitotic entry in fission yeast. Nature 459, 857–860 (2009).
Mitchison, J. M. & Nurse, P. Growth in cell length in the fission yeast Schizosaccharomyces pombe. J. Cell Sci. 75, 357–376 (1985).
Sparks, C. A., Morphew, M. & McCollum, D. Sid2p, a spindle pole body kinase that regulates the onset of cytokinesis. J. Cell Biol. 146, 777–790 (1999).
Cerutti, L. & Simanis, V. Asymmetry of the spindle pole bodies and Spg1pGAP segregation during mitosis in fission yeast. J. Cell Sci. 112, 2313–2321 (1999).
Guertin, D. A., Chang, L., Irshad, F., Gould, K. L. & McCollum, D. The role of Sid1p kinase and Cdc14p in regulating the onset of cytokinesis in fission yeast. EMBO J. 19, 1803–1815 (2000).
Grallert, A., Krapp, A., Bagley, S., Simanis, V. & Hagan, I. M. Recruitment of NIMA kinase shows that maturation of the S. pombe spindle-pole body occurs over consecutive cell cycles and reveals a role for NIMA in modulating SIN activity. Genes Dev. 18, 1007–1021 (2004).
Grallert, A. & Hagan, I. M. Schizosaccharomyces pombe NIMA-related kinase Fin1, regulates spindle formation and an affinity of Polo for the SPB. EMBO J. 21, 3096–3107 (2002).
Petersen, J. & Hagan, I. M. Polo kinase links the stress pathway to cell cycle control and tip growth in fission yeast. Nature 435, 507–512 (2005).
Sveiczer, A., Novak, B. & Mitchison, J. M. The size control of fission yeast revisited. J. Cell Sci. 109, 2947–2957 (1996).
Pines, J. & Rieder, C. L. Re-staging mitosis: a contemporary view of mitotic progression. Nature Cell Biol. 3, E3–E6 (2001).
Moreno, S., Hayles, J. & Nurse, P. Regulation of p34cdc2 protein-kinase during mitosis. Cell 58, 361–372 (1989).
Creanor, J. & Mitchison, J. M. Reduction of perturbations in leucine incorporation in synchronous cultures of Schizosaccharomyces pombe made by elutriation. J. General Microbiol. 112, 385–388 (1979).
Hagan, I. & Yanagida, M. The product of the spindle formation gene sad1+ associates with the fission yeast spindle pole body and is essential for viability. J. Cell Biol. 129, 1033–1047 (1995).
Petersen, J., Paris, J., Willer, M., Philippe, M. & Hagan, I. M. The S. pombe aurora related kinase Ark1 associates with mitotic structures in a stage dependent manner and is required for chromosome segregation. J. Cell Sci. 114, 4371–4384 (2001).
Hagan, I. M. & Asycough, K. R. in Protein localisation by fluorescence microscopy (ed. Allan, V. J.) 179–206 (Oxford Univ. Press, 2000).
Knutsen, J. H. et al. Cell-cycle analysis of fission yeast cells by flow cytometry. PLoS ONE 6, e17175 (2011).
Van Driessche, B., Tafforeau, L., Hentges, P., Carr, A. M. & Vandenhaute, J. Additional vectors for PCR-based gene tagging in Saccharomyces cerevisiae and Schizosaccharomyces pombe using nourseothricin resistance. Yeast 22, 1061–1068 (2005).
Simanis, V. & Nurse, P. The cell-cycle control gene cdc2+ of ssion yeast encodes a 13 protein-kinase potentially regulated by phosphorylation. Cell 45, 261–268 (1986).
Acknowledgements
We thank T. Toda (CRUK London Research Institute, UK), S. Martin (University of Lausanne, Switzerland), P. Nurse (Crick Institute, London, UK), D. McCollum (University of Massachusetts, USA) for strains, K. Gull (Oxford University, UK) for TAT1 antibody, T. Carr (GDSC, UK) for plasmids and B. Hodgson (Paterson Insitute) for FACs analysis. This work was supported by Cancer Research UK (CRUK) grant number C147/A6058 and Swiss National Science Foundation support to V.S.
Author information
Authors and Affiliations
Contributions
A.G. and I.M.H. conceived the study. A.G. did all of the experimentation with the exception of the mass spectrometry. Y.C. and D.L.S. did the mass spectrometry. V.S. provided essential advice and strains for the analysis of SIN function. A.G. and I.M.H. wrote the manuscript with comments and advice from V.S.
Corresponding authors
Ethics declarations
Competing interests
The authors declare no competing financial interests.
Supplementary information
Supplementary Information
Supplementary Information (PDF 1203 kb)
Supplementary Table 1
Supplementary Information (XLSX 32 kb)
Rights and permissions
About this article
Cite this article
Grallert, A., Connolly, Y., Smith, D. et al. The S. pombe cytokinesis NDR kinase Sid2 activates Fin1 NIMA kinase to control mitotic commitment through Pom1/Wee1. Nat Cell Biol 14, 738–745 (2012). https://doi.org/10.1038/ncb2514
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/ncb2514
This article is cited by
-
How do fission yeast cells grow and connect growth to the mitotic cycle?
Current Genetics (2017)
-
Dynamic phosphorylation of HP1α regulates mitotic progression in human cells
Nature Communications (2014)