Skip to main content
PMC home page
Genetics logoLink to Genetics
. 2000 Jun;155(2):623–631. doi: 10.1093/genetics/155.2.623

Slm9, a novel nuclear protein involved in mitotic control in fission yeast.

J Kanoh 1, P Russell 1
PMCID: PMC1461091  PMID: 10835386

Abstract

In the fission yeast Schizosaccharomyces pombe, as in other eukaryotic cells, Cdc2/cyclin B complex is the key regulator of mitosis. Perhaps the most important regulation of Cdc2 is the inhibitory phosphorylation of tyrosine-15 that is catalyzed by Wee1 and Mik1. Cdc25 and Pyp3 phosphatases dephosphorylate tyrosine-15 and activate Cdc2. To isolate novel activators of Cdc2 kinase, we screened synthetic lethal mutants in a cdc25-22 background at the permissive temperature (25 degrees ). One of the genes, slm9, encodes a novel protein of 807 amino acids. Slm9 is most similar to Hir2, the histone gene regulator in budding yeast. Slm9 protein level is constant and Slm9 is localized to the nucleus throughout the cell cycle. The slm9 disruptant is delayed at the G(2)-M transition as indicated by cell elongation and analysis of DNA content. Inactivation of Wee1 fully suppressed the cell elongation phenotype caused by the slm9 mutation. The slm9 mutant is defective in recovery from G(1) arrest after nitrogen starvation. The slm9 mutant is also UV sensitive, showing a defect in recovery from the cell cycle arrest after UV irradiation.

Full Text

The Full Text of this article is available as a PDF (274.5 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Aligue R., Akhavan-Niak H., Russell P. A role for Hsp90 in cell cycle control: Wee1 tyrosine kinase activity requires interaction with Hsp90. EMBO J. 1994 Dec 15;13(24):6099–6106. doi: 10.1002/j.1460-2075.1994.tb06956.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bentley N. J., Holtzman D. A., Flaggs G., Keegan K. S., DeMaggio A., Ford J. C., Hoekstra M., Carr A. M. The Schizosaccharomyces pombe rad3 checkpoint gene. EMBO J. 1996 Dec 2;15(23):6641–6651. [PMC free article] [PubMed] [Google Scholar]
  3. Boddy M. N., Furnari B., Mondesert O., Russell P. Replication checkpoint enforced by kinases Cds1 and Chk1. Science. 1998 May 8;280(5365):909–912. doi: 10.1126/science.280.5365.909. [DOI] [PubMed] [Google Scholar]
  4. Breeding C. S., Hudson J., Balasubramanian M. K., Hemmingsen S. M., Young P. G., Gould K. L. The cdr2(+) gene encodes a regulator of G2/M progression and cytokinesis in Schizosaccharomyces pombe. Mol Biol Cell. 1998 Dec;9(12):3399–3415. doi: 10.1091/mbc.9.12.3399. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Chalfie M., Tu Y., Euskirchen G., Ward W. W., Prasher D. C. Green fluorescent protein as a marker for gene expression. Science. 1994 Feb 11;263(5148):802–805. doi: 10.1126/science.8303295. [DOI] [PubMed] [Google Scholar]
  6. Choe J., Schuster T., Grunstein M. Organization, primary structure, and evolution of histone H2A and H2B genes of the fission yeast Schizosaccharomyces pombe. Mol Cell Biol. 1985 Nov;5(11):3261–3269. doi: 10.1128/mcb.5.11.3261. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Coleman T. R., Tang Z., Dunphy W. G. Negative regulation of the wee1 protein kinase by direct action of the nim1/cdr1 mitotic inducer. Cell. 1993 Mar 26;72(6):919–929. doi: 10.1016/0092-8674(93)90580-j. [DOI] [PubMed] [Google Scholar]
  8. Degols G., Russell P. Discrete roles of the Spc1 kinase and the Atf1 transcription factor in the UV response of Schizosaccharomyces pombe. Mol Cell Biol. 1997 Jun;17(6):3356–3363. doi: 10.1128/mcb.17.6.3356. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Degols G., Shiozaki K., Russell P. Activation and regulation of the Spc1 stress-activated protein kinase in Schizosaccharomyces pombe. Mol Cell Biol. 1996 Jun;16(6):2870–2877. doi: 10.1128/mcb.16.6.2870. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Dimova D., Nackerdien Z., Furgeson S., Eguchi S., Osley M. A. A role for transcriptional repressors in targeting the yeast Swi/Snf complex. Mol Cell. 1999 Jul;4(1):75–83. doi: 10.1016/s1097-2765(00)80189-6. [DOI] [PubMed] [Google Scholar]
  11. Enoch T., Nurse P. Mutation of fission yeast cell cycle control genes abolishes dependence of mitosis on DNA replication. Cell. 1990 Feb 23;60(4):665–673. doi: 10.1016/0092-8674(90)90669-6. [DOI] [PubMed] [Google Scholar]
  12. Fantes P. Epistatic gene interactions in the control of division in fission yeast. Nature. 1979 May 31;279(5712):428–430. doi: 10.1038/279428a0. [DOI] [PubMed] [Google Scholar]
  13. Featherstone C., Russell P. Fission yeast p107wee1 mitotic inhibitor is a tyrosine/serine kinase. Nature. 1991 Feb 28;349(6312):808–811. doi: 10.1038/349808a0. [DOI] [PubMed] [Google Scholar]
  14. Gould K. L., Nurse P. Tyrosine phosphorylation of the fission yeast cdc2+ protein kinase regulates entry into mitosis. Nature. 1989 Nov 2;342(6245):39–45. doi: 10.1038/342039a0. [DOI] [PubMed] [Google Scholar]
  15. Grimm C., Kohli J., Murray J., Maundrell K. Genetic engineering of Schizosaccharomyces pombe: a system for gene disruption and replacement using the ura4 gene as a selectable marker. Mol Gen Genet. 1988 Dec;215(1):81–86. doi: 10.1007/BF00331307. [DOI] [PubMed] [Google Scholar]
  16. 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. 1998 Dec;9(12):3321–3334. doi: 10.1091/mbc.9.12.3321. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Lee M. S., Enoch T., Piwnica-Worms H. mik1+ encodes a tyrosine kinase that phosphorylates p34cdc2 on tyrosine 15. J Biol Chem. 1994 Dec 2;269(48):30530–30537. [PubMed] [Google Scholar]
  18. Lopez-Girona A., Furnari B., Mondesert O., Russell P. Nuclear localization of Cdc25 is regulated by DNA damage and a 14-3-3 protein. Nature. 1999 Jan 14;397(6715):172–175. doi: 10.1038/16488. [DOI] [PubMed] [Google Scholar]
  19. Lundgren K., Walworth N., Booher R., Dembski M., Kirschner M., Beach D. mik1 and wee1 cooperate in the inhibitory tyrosine phosphorylation of cdc2. Cell. 1991 Mar 22;64(6):1111–1122. doi: 10.1016/0092-8674(91)90266-2. [DOI] [PubMed] [Google Scholar]
  20. Maeda T., Watanabe Y., Kunitomo H., Yamamoto M. Cloning of the pka1 gene encoding the catalytic subunit of the cAMP-dependent protein kinase in Schizosaccharomyces pombe. J Biol Chem. 1994 Apr 1;269(13):9632–9637. [PubMed] [Google Scholar]
  21. Matsumoto S., Yanagida M. Histone gene organization of fission yeast: a common upstream sequence. EMBO J. 1985 Dec 16;4(13A):3531–3538. doi: 10.1002/j.1460-2075.1985.tb04113.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Millar J. B., Buck V., Wilkinson M. G. Pyp1 and Pyp2 PTPases dephosphorylate an osmosensing MAP kinase controlling cell size at division in fission yeast. Genes Dev. 1995 Sep 1;9(17):2117–2130. doi: 10.1101/gad.9.17.2117. [DOI] [PubMed] [Google Scholar]
  23. Millar J. B., Lenaers G., Russell P. Pyp3 PTPase acts as a mitotic inducer in fission yeast. EMBO J. 1992 Dec;11(13):4933–4941. doi: 10.1002/j.1460-2075.1992.tb05600.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Millar J. B., McGowan C. H., Lenaers G., Jones R., Russell P. p80cdc25 mitotic inducer is the tyrosine phosphatase that activates p34cdc2 kinase in fission yeast. EMBO J. 1991 Dec;10(13):4301–4309. doi: 10.1002/j.1460-2075.1991.tb05008.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. O'Connell M. J., Raleigh J. M., Verkade H. M., Nurse P. Chk1 is a wee1 kinase in the G2 DNA damage checkpoint inhibiting cdc2 by Y15 phosphorylation. EMBO J. 1997 Feb 3;16(3):545–554. doi: 10.1093/emboj/16.3.545. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Rhind N., Russell P. Mitotic DNA damage and replication checkpoints in yeast. Curr Opin Cell Biol. 1998 Dec;10(6):749–758. doi: 10.1016/s0955-0674(98)80118-x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Rothstein R. J. One-step gene disruption in yeast. Methods Enzymol. 1983;101:202–211. doi: 10.1016/0076-6879(83)01015-0. [DOI] [PubMed] [Google Scholar]
  28. Russell P., Nurse P. Negative regulation of mitosis by wee1+, a gene encoding a protein kinase homolog. Cell. 1987 May 22;49(4):559–567. doi: 10.1016/0092-8674(87)90458-2. [DOI] [PubMed] [Google Scholar]
  29. Russell P., Nurse P. cdc25+ functions as an inducer in the mitotic control of fission yeast. Cell. 1986 Apr 11;45(1):145–153. doi: 10.1016/0092-8674(86)90546-5. [DOI] [PubMed] [Google Scholar]
  30. Sherwood P. W., Tsang S. V., Osley M. A. Characterization of HIR1 and HIR2, two genes required for regulation of histone gene transcription in Saccharomyces cerevisiae. Mol Cell Biol. 1993 Jan;13(1):28–38. doi: 10.1128/mcb.13.1.28. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Shiozaki K., Russell P. Cell-cycle control linked to extracellular environment by MAP kinase pathway in fission yeast. Nature. 1995 Dec 14;378(6558):739–743. doi: 10.1038/378739a0. [DOI] [PubMed] [Google Scholar]
  32. Spector M. S., Raff A., DeSilva H., Lee K., Osley M. A. Hir1p and Hir2p function as transcriptional corepressors to regulate histone gene transcription in the Saccharomyces cerevisiae cell cycle. Mol Cell Biol. 1997 Feb;17(2):545–552. doi: 10.1128/mcb.17.2.545. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Wu L., Russell P. Nim1 kinase promotes mitosis by inactivating Wee1 tyrosine kinase. Nature. 1993 Jun 24;363(6431):738–741. doi: 10.1038/363738a0. [DOI] [PubMed] [Google Scholar]
  34. Wu L., Russell P. Roles of Wee1 and Nim1 protein kinases in regulating the switch from mitotic division to sexual development in Schizosaccharomyces pombe. Mol Cell Biol. 1997 Jan;17(1):10–17. doi: 10.1128/mcb.17.1.10. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Wu L., Shiozaki K., Aligue R., Russell P. Spatial organization of the Nim1-Wee1-Cdc2 mitotic control network in Schizosaccharomyces pombe. Mol Biol Cell. 1996 Nov;7(11):1749–1758. doi: 10.1091/mbc.7.11.1749. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Young P. G., Fantes P. A. Schizosaccharomyces pombe mutants affected in their division response to starvation. J Cell Sci. 1987 Oct;88(Pt 3):295–304. doi: 10.1242/jcs.88.3.295. [DOI] [PubMed] [Google Scholar]

Articles from Genetics are provided here courtesy of Oxford University Press

RESOURCES