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PMID: 9560388 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Cell cycle arrest in cdc20 mutants of Saccharomyces cerevisiae is independent of Ndc10p and kinetochore function but requires a subset of spindle checkpoint genes.

Genetics ·Vol. 148 ·No. 4 ·1998-04-00 ·Pages 1701-13

Tavormina PA, Burke DJ

Abstract

The spindle checkpoint ensures accurate chromosome segregation by inhibiting anaphase onset in response to altered microtubule function and impaired kinetochore function. In this study, we report that the ability of the anti-microtubule drug nocodazole to inhibit cell cycle progression in Saccharomyces cerevisiae depends on the function of the kinetochore protein encoded by NDC10. We examined the role of the spindle checkpoint in the arrest in cdc20 mutants that arrest prior to anaphase with an aberrant spindle. The arrest in cdc20 defective cells is dependent on the BUB2 checkpoint and independent of the BUB1, BUB3, and MAD spindle checkpoint genes. We show that the lesion recognized by Bub2p is not excess microtubules, and the cdc20 arrest is independent of kinetochore function. We show that Cdc20p is not required for cyclin proteolysis at two points in the cell cycle, suggesting that CDC20 is distinct from genes encoding integral proteins of the anaphase promoting complex.

MeSH Terms
Animals Cdc20 Proteins Cell Cycle/genetics Cell Cycle Proteins/genetics DNA-Binding Proteins/genetics Epistasis, Genetic Fungal Proteins/genetics Gene Expression Regulation, Fungal Genes, Fungal Kinetochores/physiology Microtubules/physiology Rats Saccharomyces cerevisiae/drug effects,genetics,physiology Saccharomyces cerevisiae Proteins Signal Transduction Spindle Apparatus/physiology
Chemicals
BUB2 protein, S cerevisiae CBF2 protein, S cerevisiae CDC20 protein, S cerevisiae Cdc20 Proteins Cell Cycle Proteins DNA-Binding Proteins Fungal Proteins Saccharomyces cerevisiae Proteins
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Tavormina P A
Department of Biology, University of Virginia, Charlottesville 22903, USA.
Burke D J
References (69)
69 references, click to expand
  1. A fission yeast homolog of CDC20/p55CDC/Fizzy is required for recovery from DNA damage and genetically interacts with p34cdc2.
    Mol Cell Biol. 1997 Feb;17(2):742-50 PMID: 9001228
  2. Isolation and characterization of conditional-lethal mutations in the TUB1 alpha-tubulin gene of the yeast Saccharomyces cerevisiae.
    Genetics. 1988 Nov;120(3):681-95 PMID: 3066684
  3. The Schizosaccharomyces pombe spindle checkpoint protein mad2p blocks anaphase and genetically interacts with the anaphase-promoting complex.
    Proc Natl Acad Sci U S A. 1997 Jul 22;94(15):7965-70 PMID: 9223296
  4. The S. pombe cdc16 gene is required both for maintenance of p34cdc2 kinase activity and regulation of septum formation: a link between mitosis and cytokinesis?
    EMBO J. 1993 Jul;12(7):2697-704 PMID: 8334988
  5. SKP1 connects cell cycle regulators to the ubiquitin proteolysis machinery through a novel motif, the F-box.
    Cell. 1996 Jul 26;86(2):263-74 PMID: 8706131
  6. The A- and B-type cyclins of Drosophila are accumulated and destroyed in temporally distinct events that define separable phases of the G2-M transition.
    EMBO J. 1990 Aug;9(8):2563-72 PMID: 2142452
  7. Anaphase is initiated by proteolysis rather than by the inactivation of maturation-promoting factor.
    Cell. 1993 Jul 2;73(7):1393-402 PMID: 8391932
  8. Identification of a mid-anaphase checkpoint in budding yeast.
    J Cell Biol. 1997 Jan 27;136(2):345-54 PMID: 9015305
  9. Genetic and biochemical interactions between an essential kinetochore protein, Cbf2p/Ndc10p, and the CDC34 ubiquitin-conjugating enzyme.
    Mol Cell Biol. 1995 Sep;15(9):4835-42 PMID: 7651401
  10. A 20S complex containing CDC27 and CDC16 catalyzes the mitosis-specific conjugation of ubiquitin to cyclin B.
    Cell. 1995 Apr 21;81(2):279-88 PMID: 7736580
  11. A MAP kinase-dependent spindle assembly checkpoint in Xenopus egg extracts.
    Cell. 1994 Nov 4;79(3):475-86 PMID: 7954813
  12. The spindle-assembly checkpoint: aiming for a perfect mitosis, every time.
    Trends Cell Biol. 1996 Jun;6(6):228-34 PMID: 15157461
  13. TPR proteins required for anaphase progression mediate ubiquitination of mitotic B-type cyclins in yeast.
    Mol Biol Cell. 1996 May;7(5):791-801 PMID: 8744951
  14. Identification of essential components of the S. cerevisiae kinetochore.
    Cell. 1993 May 21;73(4):761-74 PMID: 8500169
  15. Mutations of the fizzy locus cause metaphase arrest in Drosophila melanogaster embryos.
    Development. 1993 Jan;117(1):359-76 PMID: 8223258
  16. The yeast TEM1 gene, which encodes a GTP-binding protein, is involved in termination of M phase.
    Mol Cell Biol. 1994 Nov;14(11):7476-82 PMID: 7935462
  17. Anaphase initiation in Saccharomyces cerevisiae is controlled by the APC-dependent degradation of the anaphase inhibitor Pds1p.
    Genes Dev. 1996 Dec 15;10(24):3081-93 PMID: 8985178
  18. Genes involved in sister chromatid separation are needed for B-type cyclin proteolysis in budding yeast.
    Cell. 1995 Apr 21;81(2):269-78 PMID: 7736579
  19. Macromolecule synthesis in temperature-sensitive mutants of yeast.
    J Bacteriol. 1967 May;93(5):1662-70 PMID: 5337848
  20. Microinjection of mitotic cells with the 3F3/2 anti-phosphoepitope antibody delays the onset of anaphase.
    J Cell Biol. 1995 Jun;129(5):1195-204 PMID: 7775567
  21. A simple and efficient procedure for transformation of yeasts.
    Biotechniques. 1992 Jul;13(1):18-20 PMID: 1503765
  22. 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
  23. Exit from mitosis is regulated by Drosophila fizzy and the sequential destruction of cyclins A, B and B3.
    EMBO J. 1995 Oct 2;14(19):4827-38 PMID: 7588612
  24. Mutations in the homologous ZDS1 and ZDS2 genes affect cell cycle progression.
    Mol Cell Biol. 1996 Oct;16(10):5254-63 PMID: 8816438
  25. Identification of subunits of the anaphase-promoting complex of Saccharomyces cerevisiae.
    Science. 1996 Nov 15;274(5290):1201-4 PMID: 8895471
  26. The cyclosome, a large complex containing cyclin-selective ubiquitin ligase activity, targets cyclins for destruction at the end of mitosis.
    Mol Biol Cell. 1995 Feb;6(2):185-97 PMID: 7787245
  27. The requirements for protein synthesis and degradation, and the control of destruction of cyclins A and B in the meiotic and mitotic cell cycles of the clam embryo.
    J Cell Biol. 1992 Feb;116(3):707-24 PMID: 1530948
  28. Tetratrico peptide repeat interactions: to TPR or not to TPR?
    Trends Biochem Sci. 1995 Jul;20(7):257-9 PMID: 7667876
  29. A novel mammalian protein, p55CDC, present in dividing cells is associated with protein kinase activity and has homology to the Saccharomyces cerevisiae cell division cycle proteins Cdc20 and Cdc4.
    Mol Cell Biol. 1994 May;14(5):3350-63 PMID: 7513050
  30. The centromere: hub of chromosomal activities.
    Science. 1995 Dec 8;270(5242):1591-4 PMID: 7502067
  31. Association of spindle assembly checkpoint component XMAD2 with unattached kinetochores.
    Science. 1996 Oct 11;274(5285):242-6 PMID: 8824188
  32. The Spg1p GTPase is an essential, dosage-dependent inducer of septum formation in Schizosaccharomyces pombe.
    Genes Dev. 1997 Jun 15;11(12):1519-34 PMID: 9203579
  33. The Drosophila cell cycle gene fizzy is required for normal degradation of cyclins A and B during mitosis and has homology to the CDC20 gene of Saccharomyces cerevisiae.
    J Cell Biol. 1995 May;129(3):725-37 PMID: 7730407
  34. Pds1p, an inhibitor of anaphase in budding yeast, plays a critical role in the APC and checkpoint pathway(s).
    J Cell Biol. 1996 Apr;133(1):99-110 PMID: 8601617
  35. S. cerevisiae genes required for cell cycle arrest in response to loss of microtubule function.
    Cell. 1991 Aug 9;66(3):507-17 PMID: 1651171
  36. Checkpoint genes required to delay cell division in response to nocodazole respond to impaired kinetochore function in the yeast Saccharomyces cerevisiae.
    Mol Cell Biol. 1995 Dec;15(12):6838-44 PMID: 8524250
  37. Checkpoints: controls that ensure the order of cell cycle events.
    Science. 1989 Nov 3;246(4930):629-34 PMID: 2683079
  38. Structure and function of kinetochores in budding yeast.
    Annu Rev Cell Dev Biol. 1995;11:471-95 PMID: 8689566
  39. Kinetochore localization of murine Bub1 is required for normal mitotic timing and checkpoint response to spindle damage.
    Cell. 1997 May 30;89(5):727-35 PMID: 9182760
  40. Aberrantly segregating centromeres activate the spindle assembly checkpoint in budding yeast.
    J Cell Biol. 1996 Apr;133(1):75-84 PMID: 8601615
  41. Molecular cloning of a cDNA with a novel domain present in the tre-2 oncogene and the yeast cell cycle regulators BUB2 and cdc16.
    Oncogene. 1995 Sep 21;11(6):1139-48 PMID: 7566974
  42. Relationship of actin and tubulin distribution to bud growth in wild-type and morphogenetic-mutant Saccharomyces cerevisiae.
    J Cell Biol. 1984 Mar;98(3):934-45 PMID: 6365931
  43. A zinc finger protein, essential for chromosome segregation, constitutes a putative DNA binding subunit of the Saccharomyces cerevisiae kinetochore complex, Cbf3.
    EMBO J. 1994 Nov 1;13(21):5203-11 PMID: 7957085
  44. Mad1p, a phosphoprotein component of the spindle assembly checkpoint in budding yeast.
    J Cell Biol. 1995 Nov;131(3):709-20 PMID: 7593191
  45. GFP tagging of budding yeast chromosomes reveals that protein-protein interactions can mediate sister chromatid cohesion.
    Curr Biol. 1996 Dec 1;6(12):1599-608 PMID: 8994824
  46. Kinetochore chemistry is sensitive to tension and may link mitotic forces to a cell cycle checkpoint.
    J Cell Biol. 1995 Aug;130(4):929-39 PMID: 7642708
  47. Yeast Hct1 is a regulator of Clb2 cyclin proteolysis.
    Cell. 1997 Aug 22;90(4):683-93 PMID: 9288748
  48. NDC10: a gene involved in chromosome segregation in Saccharomyces cerevisiae.
    J Cell Biol. 1993 May;121(3):503-12 PMID: 8486732
  49. Identification of a human mitotic checkpoint gene: hsMAD2.
    Science. 1996 Oct 11;274(5285):246-8 PMID: 8824189
  50. Two genes required for the binding of an essential Saccharomyces cerevisiae kinetochore complex to DNA.
    Proc Natl Acad Sci U S A. 1995 Dec 19;92(26):12026-30 PMID: 8618837
  51. Closing the cell cycle circle in yeast: G2 cyclin proteolysis initiated at mitosis persists until the activation of G1 cyclins in the next cycle.
    Cell. 1994 Jul 1;77(7):1037-50 PMID: 8020094
  52. CDC27Hs colocalizes with CDC16Hs to the centrosome and mitotic spindle and is essential for the metaphase to anaphase transition.
    Cell. 1995 Apr 21;81(2):261-8 PMID: 7736578
  53. Saccharomyces cerevisiae genes required in the absence of the CIN8-encoded spindle motor act in functionally diverse mitotic pathways.
    Mol Biol Cell. 1997 Jun;8(6):1035-50 PMID: 9201714
  54. The Saccharomyces cerevisiae spindle pole body duplication gene MPS1 is part of a mitotic checkpoint.
    J Cell Biol. 1996 Jan;132(1-2):111-23 PMID: 8567717
  55. Abnormal kinetochore structure activates the spindle assembly checkpoint in budding yeast.
    Mol Biol Cell. 1996 Aug;7(8):1195-208 PMID: 8856664
  56. The role of CDC28 and cyclins during mitosis in the budding yeast S. cerevisiae.
    Cell. 1991 Apr 5;65(1):145-61 PMID: 1849457
  57. Budding yeast SKP1 encodes an evolutionarily conserved kinetochore protein required for cell cycle progression.
    Cell. 1996 Jul 26;86(2):275-85 PMID: 8706132
  58. A delay in the Saccharomyces cerevisiae cell cycle that is induced by a dicentric chromosome and dependent upon mitotic checkpoints.
    Mol Cell Biol. 1992 Sep;12(9):3857-64 PMID: 1324407
  59. A shared domain between a spindle assembly checkpoint protein and Ypt/Rab-specific GTPase-activators.
    Trends Biochem Sci. 1997 Jul;22(7):243-4 PMID: 9255064
  60. A chicken-yeast chimeric beta-tubulin protein is incorporated into mouse microtubules in vivo.
    Cell. 1986 Feb 14;44(3):461-8 PMID: 3753663
  61. Three-dimensional analysis and ultrastructural design of mitotic spindles from the cdc20 mutant of Saccharomyces cerevisiae.
    Mol Biol Cell. 1997 Jan;8(1):1-11 PMID: 9017591
  62. The dynamics of chromosome movement in the budding yeast Saccharomyces cerevisiae.
    J Cell Biol. 1989 Dec;109(6 Pt 2):3355-66 PMID: 2689456
  63. The CDC20 gene product of Saccharomyces cerevisiae, a beta-transducin homolog, is required for a subset of microtubule-dependent cellular processes.
    Mol Cell Biol. 1991 Nov;11(11):5592-602 PMID: 1922065
  64. CEP3 encodes a centromere protein of Saccharomyces cerevisiae.
    J Cell Biol. 1995 Mar;128(5):749-60 PMID: 7876302
  65. From DNA damage to cell cycle arrest and suicide: a budding yeast perspective.
    Curr Opin Genet Dev. 1996 Feb;6(1):4-11 PMID: 8791492
  66. The checkpoint delaying anaphase in response to chromosome monoorientation is mediated by an inhibitory signal produced by unattached kinetochores.
    J Cell Biol. 1995 Aug;130(4):941-8 PMID: 7642709
  67. Differential requirements for DNA replication in the activation of mitotic checkpoints in Saccharomyces cerevisiae.
    Mol Cell Biol. 1997 Jun;17(6):3315-22 PMID: 9154830
  68. Isolation and characterization of a gene (CBF2) specifying a protein component of the budding yeast kinetochore.
    J Cell Biol. 1993 May;121(3):513-9 PMID: 8486733
  69. The Saccharomyces cerevisiae kinetochore.
    FEBS Lett. 1996 Jun 24;389(1):70-4 PMID: 8682209
Article Info
Journal
Genetics
Abbr.
Genetics
ISSN
0016-6731
DOI
10.1093/genetics/148.4.1701
Published
1998-04-00
Pages
1701-13
Language
English
Region
United States
NLM ID
0374636
PMCID
PMC1460108
Subset
IM
Grants
NIGMS NIH HHS · GM-40334 · United States
External Links
PubMed source DOI: 10.1093/genetics/148.4.1701 PMC Full Text View journal details
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