Skip to main content
The Journal of Cell Biology logoLink to The Journal of Cell Biology
. 1996 Jan 1;132(1):111–123. doi: 10.1083/jcb.132.1.111

The Saccharomyces cerevisiae spindle pole body duplication gene MPS1 is part of a mitotic checkpoint

PMCID: PMC2120695  PMID: 8567717

Abstract

M-phase checkpoints inhibit cell division when mitotic spindle function is perturbed. Here we show that the Saccharomyces cerevisiae MPS1 gene product, an essential protein kinase required for spindle pole body (SPB) duplication (Winey et al., 1991; Lauze et al., 1995), is also required for M-phase check-point function. In cdc31-2 and mps2-1 mutants, conditional failure of SPB duplication results in cell cycle arrest with high p34CDC28 kinase activity that depends on the presence of the wild-type MAD1 checkpoint gene, consistent with checkpoint arrest of mitosis. In contrast, mps1 mutant cells fail to duplicate their SPBs and do not arrest division at 37 degrees C, exhibiting a normal cycle of p34CDC28 kinase activity despite the presence of a monopolar spindle. Double mutant cdc31-2, mps1-1 cells also fail to arrest mitosis at 37 degrees C, despite having SPB structures similar to cdc31-2 single mutants as determined by EM analysis. Arrest of mitosis upon microtubule depolymerization by nocodazole is also conditionally absent in mps1 strains. This is observed in mps1 cells synchronized in S phase with hydroxyurea before exposure to nocodazole, indicating that failure of checkpoint function in mps1 cells is independent of SPB duplication failure. In contrast, hydroxyurea arrest and a number of other cdc mutant arrest phenotypes are unaffected by mps1 alleles. We propose that the essential MPS1 protein kinase functions both in SPB duplication and in a mitotic checkpoint monitoring spindle integrity.

Full Text

The Full Text of this article is available as a PDF (1.6 MB).

Selected References

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

  1. Andreassen P. R., Margolis R. L. Microtubule dependency of p34cdc2 inactivation and mitotic exit in mammalian cells. J Cell Biol. 1994 Nov;127(3):789–802. doi: 10.1083/jcb.127.3.789. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Balczon R., Bao L., Zimmer W. E., Brown K., Zinkowski R. P., Brinkley B. R. Dissociation of centrosome replication events from cycles of DNA synthesis and mitotic division in hydroxyurea-arrested Chinese hamster ovary cells. J Cell Biol. 1995 Jul;130(1):105–115. doi: 10.1083/jcb.130.1.105. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Baum P., Yip C., Goetsch L., Byers B. A yeast gene essential for regulation of spindle pole duplication. Mol Cell Biol. 1988 Dec;8(12):5386–5397. doi: 10.1128/mcb.8.12.5386. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Byers B., Goetsch L. Behavior of spindles and spindle plaques in the cell cycle and conjugation of Saccharomyces cerevisiae. J Bacteriol. 1975 Oct;124(1):511–523. doi: 10.1128/jb.124.1.511-523.1975. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Forsburg S. L., Nurse P. Cell cycle regulation in the yeasts Saccharomyces cerevisiae and Schizosaccharomyces pombe. Annu Rev Cell Biol. 1991;7:227–256. doi: 10.1146/annurev.cb.07.110191.001303. [DOI] [PubMed] [Google Scholar]
  6. Gard D. L., Hafezi S., Zhang T., Doxsey S. J. Centrosome duplication continues in cycloheximide-treated Xenopus blastulae in the absence of a detectable cell cycle. J Cell Biol. 1990 Jun;110(6):2033–2042. doi: 10.1083/jcb.110.6.2033. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Hadwiger J. A., Wittenberg C., Mendenhall M. D., Reed S. I. The Saccharomyces cerevisiae CKS1 gene, a homolog of the Schizosaccharomyces pombe suc1+ gene, encodes a subunit of the Cdc28 protein kinase complex. Mol Cell Biol. 1989 May;9(5):2034–2041. doi: 10.1128/mcb.9.5.2034. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Hardwick K. G., Murray A. W. Mad1p, a phosphoprotein component of the spindle assembly checkpoint in budding yeast. J Cell Biol. 1995 Nov;131(3):709–720. doi: 10.1083/jcb.131.3.709. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Hartwell L. H., Weinert T. A. Checkpoints: controls that ensure the order of cell cycle events. Science. 1989 Nov 3;246(4930):629–634. doi: 10.1126/science.2683079. [DOI] [PubMed] [Google Scholar]
  10. Hoyt M. A., Totis L., Roberts B. T. S. cerevisiae genes required for cell cycle arrest in response to loss of microtubule function. Cell. 1991 Aug 9;66(3):507–517. doi: 10.1016/0092-8674(81)90014-3. [DOI] [PubMed] [Google Scholar]
  11. Hutter K. J., Eipel H. E. Microbial determinations by flow cytometry. J Gen Microbiol. 1979 Aug;113(2):369–375. doi: 10.1099/00221287-113-2-369. [DOI] [PubMed] [Google Scholar]
  12. Irniger S., Piatti S., Michaelis C., Nasmyth K. Genes involved in sister chromatid separation are needed for B-type cyclin proteolysis in budding yeast. Cell. 1995 Apr 21;81(2):269–278. doi: 10.1016/0092-8674(95)90337-2. [DOI] [PubMed] [Google Scholar]
  13. Jacobs C. W., Adams A. E., Szaniszlo P. J., Pringle J. R. Functions of microtubules in the Saccharomyces cerevisiae cell cycle. J Cell Biol. 1988 Oct;107(4):1409–1426. doi: 10.1083/jcb.107.4.1409. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Jordan M. A., Thrower D., Wilson L. Effects of vinblastine, podophyllotoxin and nocodazole on mitotic spindles. Implications for the role of microtubule dynamics in mitosis. J Cell Sci. 1992 Jul;102(Pt 3):401–416. doi: 10.1242/jcs.102.3.401. [DOI] [PubMed] [Google Scholar]
  15. Kelly T. J., Martin G. S., Forsburg S. L., Stephen R. J., Russo A., Nurse P. The fission yeast cdc18+ gene product couples S phase to START and mitosis. Cell. 1993 Jul 30;74(2):371–382. doi: 10.1016/0092-8674(93)90427-r. [DOI] [PubMed] [Google Scholar]
  16. King R. W., Jackson P. K., Kirschner M. W. Mitosis in transition. Cell. 1994 Nov 18;79(4):563–571. doi: 10.1016/0092-8674(94)90542-8. [DOI] [PubMed] [Google Scholar]
  17. Langan T. A., Gautier J., Lohka M., Hollingsworth R., Moreno S., Nurse P., Maller J., Sclafani R. A. Mammalian growth-associated H1 histone kinase: a homolog of cdc2+/CDC28 protein kinases controlling mitotic entry in yeast and frog cells. Mol Cell Biol. 1989 Sep;9(9):3860–3868. doi: 10.1128/mcb.9.9.3860. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Lauzé E., Stoelcker B., Luca F. C., Weiss E., Schutz A. R., Winey M. Yeast spindle pole body duplication gene MPS1 encodes an essential dual specificity protein kinase. EMBO J. 1995 Apr 18;14(8):1655–1663. doi: 10.1002/j.1460-2075.1995.tb07154.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Li J. J., Deshaies R. J. Exercising self-restraint: discouraging illicit acts of S and M in eukaryotes. Cell. 1993 Jul 30;74(2):223–226. doi: 10.1016/0092-8674(93)90413-k. [DOI] [PubMed] [Google Scholar]
  20. Li R., Murray A. W. Feedback control of mitosis in budding yeast. Cell. 1991 Aug 9;66(3):519–531. doi: 10.1016/0092-8674(81)90015-5. [DOI] [PubMed] [Google Scholar]
  21. Luca F. C. Does degradation lead to segregation? Curr Biol. 1993 Oct 1;3(10):716–718. doi: 10.1016/0960-9822(93)90078-3. [DOI] [PubMed] [Google Scholar]
  22. Maniotis A., Schliwa M. Microsurgical removal of centrosomes blocks cell reproduction and centriole generation in BSC-1 cells. Cell. 1991 Nov 1;67(3):495–504. doi: 10.1016/0092-8674(91)90524-3. [DOI] [PubMed] [Google Scholar]
  23. Mazia D. The chromosome cycle and the centrosome cycle in the mitotic cycle. Int Rev Cytol. 1987;100:49–92. doi: 10.1016/s0074-7696(08)61698-8. [DOI] [PubMed] [Google Scholar]
  24. Navas T. A., Zhou Z., Elledge S. J. DNA polymerase epsilon links the DNA replication machinery to the S phase checkpoint. Cell. 1995 Jan 13;80(1):29–39. doi: 10.1016/0092-8674(95)90448-4. [DOI] [PubMed] [Google Scholar]
  25. Nicklas R. B., Ward S. C. Elements of error correction in mitosis: microtubule capture, release, and tension. J Cell Biol. 1994 Sep;126(5):1241–1253. doi: 10.1083/jcb.126.5.1241. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Nurse P. Ordering S phase and M phase in the cell cycle. Cell. 1994 Nov 18;79(4):547–550. doi: 10.1016/0092-8674(94)90539-8. [DOI] [PubMed] [Google Scholar]
  27. Oakley B. R., Oakley C. E., Yoon Y., Jung M. K. Gamma-tubulin is a component of the spindle pole body that is essential for microtubule function in Aspergillus nidulans. Cell. 1990 Jun 29;61(7):1289–1301. doi: 10.1016/0092-8674(90)90693-9. [DOI] [PubMed] [Google Scholar]
  28. Poch O., Schwob E., de Fraipont F., Camasses A., Bordonné R., Martin R. P. RPK1, an essential yeast protein kinase involved in the regulation of the onset of mitosis, shows homology to mammalian dual-specificity kinases. Mol Gen Genet. 1994 Jun 15;243(6):641–653. doi: 10.1007/BF00279573. [DOI] [PubMed] [Google Scholar]
  29. Rieder C. L., Alexander S. P. The attachment of chromosomes to the mitotic spindle and the production of aneuploidy in newt lung cells. Prog Clin Biol Res. 1989;318:185–194. [PubMed] [Google Scholar]
  30. Rieder C. L., Schultz A., Cole R., Sluder G. Anaphase onset in vertebrate somatic cells is controlled by a checkpoint that monitors sister kinetochore attachment to the spindle. J Cell Biol. 1994 Dec;127(5):1301–1310. doi: 10.1083/jcb.127.5.1301. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Saka Y., Fantes P., Sutani T., McInerny C., Creanor J., Yanagida M. Fission yeast cut5 links nuclear chromatin and M phase regulator in the replication checkpoint control. EMBO J. 1994 Nov 15;13(22):5319–5329. doi: 10.1002/j.1460-2075.1994.tb06866.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Saka Y., Yanagida M. Fission yeast cut5+, required for S phase onset and M phase restraint, is identical to the radiation-damage repair gene rad4+. Cell. 1993 Jul 30;74(2):383–393. doi: 10.1016/0092-8674(93)90428-s. [DOI] [PubMed] [Google Scholar]
  33. Schild D., Ananthaswamy H. N., Mortimer R. K. An endomitotic effect of a cell cycle mutation of Saccharomyces cerevisiae. Genetics. 1981 Mar-Apr;97(3-4):551–562. doi: 10.1093/genetics/97.3-4.551. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Sluder G., Miller F. J., Cole R., Rieder C. L. Protein synthesis and the cell cycle: centrosome reproduction in sea urchin eggs is not under translational control. J Cell Biol. 1990 Jun;110(6):2025–2032. doi: 10.1083/jcb.110.6.2025. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Weinert T. A., Hartwell L. H. Cell cycle arrest of cdc mutants and specificity of the RAD9 checkpoint. Genetics. 1993 May;134(1):63–80. doi: 10.1093/genetics/134.1.63. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Weinert T. A., Hartwell L. H. The RAD9 gene controls the cell cycle response to DNA damage in Saccharomyces cerevisiae. Science. 1988 Jul 15;241(4863):317–322. doi: 10.1126/science.3291120. [DOI] [PubMed] [Google Scholar]
  37. Weinert T. A., Kiser G. L., Hartwell L. H. Mitotic checkpoint genes in budding yeast and the dependence of mitosis on DNA replication and repair. Genes Dev. 1994 Mar 15;8(6):652–665. doi: 10.1101/gad.8.6.652. [DOI] [PubMed] [Google Scholar]
  38. Winey M., Goetsch L., Baum P., Byers B. MPS1 and MPS2: novel yeast genes defining distinct steps of spindle pole body duplication. J Cell Biol. 1991 Aug;114(4):745–754. doi: 10.1083/jcb.114.4.745. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from The Journal of Cell Biology are provided here courtesy of The Rockefeller University Press

RESOURCES