Cell Cycle Control and Mitosis

  • Randy Strich


The mitotic cell cycle is designed to produce two cells, each containing a faithfully duplicated nuclear genome and a complete compliment of cytoplasmic organelles such as mitochondria. Given the fundamental importance of this process to the normal growth and development of all organisms, it is not surprising that the basic structure of the cell cycle has been conserved in all eucaryotes from yeast to man. This chapter focuses on the regulatory aspects governing cell cycle progression.


Restriction Point Cell Cycle Control CELl CYClE Origin Recognition Complex CELl CYClE CONTROl 
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  1. 1.
    Pardee AB: G1 events and regulation of cell proliferation. Science 1989, 246: 603–608.PubMedCrossRefGoogle Scholar
  2. 2.
    Hartwell L: Genetic control of cell division cycle in yeast. II. Genes controlling DNA replication and its initiation. J Mol Biol 1971, 59: 183–194.PubMedCrossRefGoogle Scholar
  3. 3.
    Masui Y, Markert C: Cytoplasmic control of nuclear behavior during meiotic maturation of frog oocytes. J Exp Zool 1971, 177: 129–146.PubMedCrossRefGoogle Scholar
  4. 4.
    Foe VE, Odell GM, Edgar BA: Cell Cycle Reguation in Early Development. In The Development of Drosophila melanogaster. Edited by Bate M, Martinez Arias A. Cold Spring Harbor, NY: Cold Spring Harbor Laboratory Press; 1993: 149–300.Google Scholar
  5. 5.
    Foe VE: Mitotic domains reveal early commitment of cells in Drosophila embryos. Development 1989, 107: 1–22.PubMedGoogle Scholar
  6. 6.
    Graves BJ, Schubiger G: Cell cycle changes during growth and differentiation of imaginal leg discs in Drosophila melanogaster. Dev Biol 1982, 93: 104–110.Google Scholar
  7. 7.
    Pines J: Cyclins and cyclin-dependent kinases: take your partners. TIBS 1993, 18: 195–197.PubMedGoogle Scholar
  8. 8.
    Lew DJ, Dulic V, Reed SI: Isolation of three novel human cyclins by rescue of G1 cyclin (On) function in yeast. Cell 1991, 66: 1197–1206.PubMedCrossRefGoogle Scholar
  9. Koff A, Cross F, Fisher A, et al.: Human cyclin E, a new cyclin that interacts with two members of the CDC2 gene family. Cell 1991, 66:1217–1228.Google Scholar
  10. 10.
    Walker DH, Maller JL: Role for cyclin A in the dependence of mitosis on completion of DNA replication. Nature 1991, 354: 314–317.PubMedCrossRefGoogle Scholar
  11. Draetta G, Luca F, Westendorf J, et al.: Cdc2 protein kinase is complexed with both cyclin A and B: evidence for proteolytic inactivation of MPF. Cell 1989, 56:829–838.Google Scholar
  12. 12.
    Xiong Y, Zhang H, Beach D: D-type cyclins associated with multiple protein kinases and the DNA replication and repair factor PCNA. Cell 1992, 71: 505–514.PubMedCrossRefGoogle Scholar
  13. 13.
    Hofmann F, Livingston DM: Differential effects of CDK2 and CDK3 on the control of pRb and E2F function during G1 exit. Genes Dev 1996, 10: 851–861.PubMedCrossRefGoogle Scholar
  14. Yamasaki L, Jacks T, Bronson R, et al.: Tumor induction and tissue atrophy in mice lacking E2F-1. Cell 1996, 85:537–548.Google Scholar
  15. 15.
    Stinchcomb D, Maim C, Davis R: Centromeric DNA from Saccharomcyes cerevisiae. J Mol Biol 1982, 158: 157–179.CrossRefGoogle Scholar
  16. 16.
    Bell SP, Stillman B: ATP-dependent recognition of eukaryotic origins of DNA replication by a multiprotein complex. Nature 1992, 357: 128–134.PubMedCrossRefGoogle Scholar
  17. Rowles A, Chong JP, Brown L, et al.: Interaction between the origin recognition complex and the replication licensing system in Xenopus. Cell 1996, 87:287–296.Google Scholar
  18. Gossen M, Pak DT, Hansen SK, et al.: A Drosophila homolog of the yeast origin recognition complex. Science 1995, 270:1674–1677.Google Scholar
  19. 19.
    Liang C, Weinreich M, Stillman B: ORC and Cdc6p interact and determine the frequency of initiation of DNA replication in the genome. Cell 1995, 81: 667–676.PubMedCrossRefGoogle Scholar
  20. 20.
    Piatti S, Lengauer C, Nasmyth K: Cdc6 is an unstable protein whose de novo synthesis in G1 is important for the onset of S-phase and for preventing a ‘reductional’ anaphase in the budding yeast Saccharomyces cerevisiae. EMBO J 1995, 14: 3788–3799.Google Scholar
  21. 21.
    Madine MA, Khoo CY, Mills AD, Laskey RA: MCM3 complex required for cell cycle regulation of DNA replication in vertebrate cells. Nature 1995, 375: 421–424.PubMedCrossRefGoogle Scholar
  22. 22.
    Dahmann C, Diffley JF, Nasmyth KA: S-phase-promoting cyclin-dependent kinases prevent re-replication by inhibiting the transition of replication origins to a prereplicative state. Curr Biol 1995, 5: 1257–1269.PubMedCrossRefGoogle Scholar
  23. 23.
    Adachi Y, Laemmli UK: Study of the cell cycle-depen- dent assembly of the DNA pre-replication centres in Xenopus egg extracts. EMBO J 1994, 13: 4153–4164.PubMedGoogle Scholar
  24. 24.
    Vernos I, Karsenti E: Motors involved in spindle assembly and chromosome segregation. Curr Opin Cell Biol 1996, 8: 4–9.PubMedCrossRefGoogle Scholar
  25. 25.
    Enos AP, Morris NR: Mutation of a gene that encodes a kinesin-like protein blocks nuclear division in A. nidulans. Cell 1990, 60: 1019–1027.CrossRefGoogle Scholar
  26. Yen TJ, Li G, Schaar BT, et al.: CENP-E is a putative kinetochore motor that accumulates just before mitosis. Nature 1992, 359:536–539.Google Scholar
  27. 27.
    Sawin KE, Mitchison TJ: Mutations in the kinesin-like protein Eg5 disrupting localization to the mitotic spindle. Proc Natl Acad Sci USA 1995, 92: 4289–4293.PubMedCrossRefGoogle Scholar
  28. 28.
    Booher RN, Alfa CE, Hyams JS, Beach DH: The fission yeast cdc2/cdc13/sucl protein kinase: regulation of catalytic activity and nuclear localization. Cell1989, 58: 485–497.Google Scholar
  29. Kobayashi H, Stewert E, Poon R, et al.: Identification of the domains in cyclin A required for binding to, and activation of, p34cdc2 and p32cDK2 protein kinase subunits. Mol Biol Cell 1992, 3:1279–1294.Google Scholar
  30. Dowdy SF, Hinds PW, Louie K, et al.: Physical interaction of the retinoblastoma protein with human D cyclins. Cell 1993, 73:499–511.Google Scholar
  31. 31.
    Solomon MJ, Harper JW, Shuttleworth J: CAK, the p34cdc2 activating kinase, contains a protein identical or closely related to p40MOl5 EMBO J 1993, 12: 3133–3142.PubMedGoogle Scholar
  32. 32.
    Fisher RP, Morgan DO: A novel cyclin associates with M015/CDK7 to form the CDK-activating kinase. Cell 1994, 78: 713–724.PubMedCrossRefGoogle Scholar
  33. 33.
    Sutton A, Freiman R: The Caklp protein kinase is required at Gl/S and G2/M in the budding yeast cell cycle. Genetics 1997, 147: 57–71.PubMedGoogle Scholar
  34. Larochelle S, Pandur J, Fisher RP, et al.: CDK7 is essential for mitosis and for I CDK-activating kinase activity. Genes Dev 1998, 12:370–381.Google Scholar
  35. 35.
    Russell P, Nurse P: Negative regulation of mitosis by weel+, a gene encoding a protein kinase homolog. Cell 1987, 49: 559–567.PubMedCrossRefGoogle Scholar
  36. Igarashi M, Nagata A, Jinno S, et al.: Weel(+)-like gene in human cells. Nature 1991, 353:80–83.Google Scholar
  37. 37.
    Russell P, Nurse P: Cdc25+ functions as an inducer in the mitotic control of fission yeast. Cell 1986, 45: 145–153.PubMedCrossRefGoogle Scholar
  38. Hoffmann I, Clarke PR, Marcote MJ, et al.: Phosphorylation and activation of human cdc25-C by cdc2-cyclin B and its involvement in the self-amplification of MPF at mitosis. EMBO J 1993, 12:53–63.Google Scholar
  39. 39.
    Tang Z, Coleman TR, Dunphy WG: Two distinct mechanisms for negative regulation of the Wee1 protein kinase. EMBO J 1993, 12: 3427–3436.PubMedGoogle Scholar
  40. 40.
    Koch C, Schleiffer A, Ammerer G, Nasmyth K: Switching transcription on and off during the yeast cell cycle: Cln/Cdc28 kinases activate bound transcription factor SBF (Swi4/Swi6) at start, whereas Clb/Cdc28 kinases displace it from the promoter in G2. Genes Den 1996, 10: 129–141.CrossRefGoogle Scholar
  41. 41.
    Ohtsubo M, Roberts JM: Cyclin-dependent regulation of G1 in mammalian fibroblasts. Science 1993, 259: 1908–1912.PubMedCrossRefGoogle Scholar
  42. Ghiara JB, Richardson HE, Sugimoto K, et al.: A cyclin B homolog in S. cerevisiae: chronic activation of the Cdc28 protein kinase by cyclin prevents exit from mitosis. Cell 1991, 65:163–174.Google Scholar
  43. 43.
    Glotzer M, Murray AW, Kirschner MW: Cyclin is degraded by the ubiquitin pathway. Nature 1991, 349: 132–138.PubMedCrossRefGoogle Scholar
  44. 44.
    Glotzer M: Cell cycle: the only way out of mitosis. Curr Biol 1995, 5: 970–972.PubMedCrossRefGoogle Scholar
  45. 45.
    Hockstrasser M: Ubiquitin, proteosomes, and the regulation of intracellular protein degradation. Curr Opin Cell Biol 1995, 7: 215–223.CrossRefGoogle Scholar
  46. Edgar BA, Sprenger F, Duronio RJ, et al.: Distinct molecular mechanism regulates cell cycle timing at successive stages of Drosophila embryogenesis. Genes Dev 1994, 8:440–452.Google Scholar
  47. 47.
    Matthias P, Herskowitz I: Joining the complex: cyclindependent kinase inhibitory proteins and the cell cycle. Cell 1994, 79: 181–184.CrossRefGoogle Scholar
  48. 48.
    Mendenhall MD. An inhibitor of p34c1x28 protein kinase activity from Saccharomyces cerevisiae. Science 1993, 259: 216–219.Google Scholar
  49. Kato JY, Matsuoka M, Polyak K, et al.: Cyclic AMP-induced G1 phase arrest mediated by an inhibitor (p27Kip1) of cyclin-dependent kinase 4 activation. Cell 1994, 79:487–496.Google Scholar
  50. el-Deiry WS, Tokino T, Velculescu VE, et al.: WAF1, a potential mediator of p53 tumor suppression. Cell 1993, 75:817–825.Google Scholar
  51. 51.
    Serrano M, Hannon GJ, Beach D: A new regulatory motif in cell-cycle control causing specific inhibition of cyclin D/CDK4. Nature 1993, 366: 704–707.PubMedCrossRefGoogle Scholar
  52. Kamb A, Guris NA, Weaver-Feldhaus J, et al.: A cell cycle regulator potentially involved in genesis of many tumor types. Science 1994, 264:436–440.Google Scholar
  53. Ellis R, DeFeo D, Shih T, et al.: The p21 src genes of Harvey and Kirsten sarcoma viruses originate from divergent members of the family of normal vertebrate genes. Nature 1981, 292:506–511.Google Scholar
  54. Alitalo K, Ramsay G, Bishop JM, et al.: Identification of nuclear proteins encoded by viral and cellular myc oncogenes. Nature 1983, 306:274–277.Google Scholar
  55. 55.
    Lukas J, Barkova J, Bartek J: Convergence of mitogenic signalling cascades from diverse classes of receptors on the cyclin D-CDK-pRb-controlled G1 checkpoint. Mol Cell Biol 1996, 16: 6917–6925.PubMedGoogle Scholar
  56. Matsushime H, Ewen ME, Strom DK, et al.: Identification and properties of an atypical catalytic subunit (p34PSK-J3/CDK4) for mammalian D type G1 cyclins. Cell 1992, 71:323–334.Google Scholar
  57. Polyak K, Lee MH, Erdjument-Bromage H, et al.: Cloning of p27Kip1, a cyclin-dependent kinase inhibitor and a potential mediator of extracellular antimitogenic signals. Cell 1994, 78:59–66.Google Scholar
  58. 58.
    Toyoshima H, Hunter T: P27, a novel inhibitor of G1 cyclin-CDK protein kinase activity, is related to p21. Cell 1994, 78: 67–74.PubMedCrossRefGoogle Scholar
  59. Chen PL, Scully P, Shew JY, et al.: Phosphorylation of the retinoblastoma gene product is modulated during the cell cycle and cellular differentiation. Cell 1989, 58:1193–1198.Google Scholar
  60. 60.
    Hershko A: Roles of ubiquitin-mediated proteolysis in cell cycle control. Curr Opin Cell Biol 1997, 9: 788–799.PubMedCrossRefGoogle Scholar
  61. 61.
    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, 81: 269–278.PubMedCrossRefGoogle Scholar
  62. 62.
    Visintin R, Prinz S, Amon A: CDC20 and CDH1: a family of substrate-specific activators of APC-dependent proteolysis. Science 1997, 278: 460–463.PubMedCrossRefGoogle Scholar
  63. 63.
    Yamamoto A, Guacci V, Koshland D: Pds1p is required for faithful execution of anaphase in the yeast, Saccharomyces cerevisiae. J Cell Biol 1996, 133: 85–97.CrossRefGoogle Scholar
  64. 64.
    Schwab M, Schulze Lutum A, Seufert W: Yeast Hct1 is a regulator of Clb2 cyclin proteolysis. Cell 1997, 90: 683–693.PubMedCrossRefGoogle Scholar
  65. Weinstein J, Jacobsen FW, Hsu-Chen J, et al.: 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, 14:3350–3363.Google Scholar
  66. 66.
    Dawson IA, Roth S, Artavanis-Tsakonas S: 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, 129: 725–737.CrossRefGoogle Scholar
  67. 67.
    Shirayama M, Zachariae W, Ciosk R, Nasmyth K: The Polo-like kinase Cdc5p and the WD-repeat protein Cdc2Op/fizzy are regulators and substrates of the anaphase promoting complex in Saccharomyces cerevisiae. EMBO J 1998, 17: 1336–1349.CrossRefGoogle Scholar
  68. 68.
    Weinert TA, Hartwell LH: The RAD9 gene controls the cell cycle response to DNA damage in Saccharomyces cerevisiae. Science 1988, 241: 317–322.Google Scholar
  69. 69.
    Weinert TA, Hartwell LH: Cell cycle arrest of cdc mutants and specificity of the RAD9 checkpoint. Genetics 1993, 134: 63–80.PubMedGoogle Scholar
  70. 70.
    Hartwell LH, Weinert TA: Checkpoints: controls that ensure the order of cell cycle events. Science 1989, 246: 629–634.PubMedCrossRefGoogle Scholar
  71. 71.
    Weinert TA, Kiser GL, Hartwell LH: Mitotic checkpoint genes in budding yeast and the dependence of mitosis on DNA replication and repair. Genes Dev 1994, 8: 652–665.PubMedCrossRefGoogle Scholar
  72. 72.
    Paulovich AG, Hartwell LH: A checkpoint regulates the rate of progression through S phase in S. cerevisiae in response to DNA damage. Cell 1995, 82: 841–847.PubMedCrossRefGoogle Scholar
  73. Savitsky K, Bar-Shira A, Gilad S, et al.: A single ataxia telangiectasia gene with a product similar to PI-3 kinase. Science 1995, 268:1749–1753.Google Scholar
  74. Allen JB, Zhou Z, Siede W, et al.: The SAD1/RAD53 protein kinase controls multiple checkpoints and DNA damage-induced transcription in yeast. Genes Dev 1994, 8:2401–2415.Google Scholar
  75. 75.
    Painter RB, Young BR: Radiosensitivity in ataxiatelangiectasia: a new explanation. Proc Natl Acad Sci USA 1980, 77: 7315–7317.PubMedCrossRefGoogle Scholar
  76. 76.
    Yin Y, Tainsky MA, Bischoff FZ, et al.: Wild-type p53 restores cell cycle control and inhibits gene amplification in cells with mutant p.53 alleles. Cell 1992, 70:937–948.Google Scholar

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© Current Medicine, Inc. 2000

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  • Randy Strich

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