Mitotic Chromosome Segregation Control

  • Yu Xue
  • Chuanhai Fu
  • Yong Miao
  • Jianhui Yao
  • Zhen Dou
  • Jie Zhang
  • Larry Brako
  • Xuebiao Yao


The somatic division, called mitosis, is characterized by equal distribution of parental genome into two daughter cells. Mitosis involves a dramatic reorganization of both nucleus and cytoplasm driven by protein kinase cascades including master controller Cdkl-cyclin B. Mitosis is an ancient eukaryotic event, and some divergence emerged during evolution. Many single cell eukaryotes, including yeast and slime molds, undergo a closed mitosis, in which mitotic spindle formation and chromosome segregation occur within an intact nuclear envelope. However, higher eukaryotes such as animal and plant cells use open mitosis, in which nuclear envelope disassembles before the chromosomes segregate. This review primarily focuses on mitotic chromosome segregation in animal cells and refers to other organisms when regulation is mechanistically conserved. For convenience of discussion, mitotic chromosome dynamics are subdivided into six phases: prophase, prometaphase, metaphase, anaphase, telophase and cytokinesis.


Adenomatous Polyposis Coli Spindle Pole Spindle Assembly Checkpoint Spindle Checkpoint Mitotic Checkpoint 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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  1. Abrieu A, Kahana JA, Wood KW, Cleveland DW (2000) CENP-E as an essential component of the mitotic checkpoint in vitro. Cell 102:817–826PubMedGoogle Scholar
  2. Abrieu A, Magnaghi-Jaulin L, Kahana JA, Peter M, Castro A, Vigneron S, Lorca T, Cleveland DW, Labbe J (2001) Mpsl is a kinetochore-associated kinase essential for the vertebrate mitotic checkpoint. Cell 106:83–93PubMedGoogle Scholar
  3. Andrews PD, Ovechkina Y, Morrice N, Wagenbach M, Duncan K, Wordeman L, Swedlow JR. (2004) Aurora B regulates MCAK at the mitotic centromere. Dev Cell 6:253–68PubMedGoogle Scholar
  4. Afshar K, Barton NR, Hawley RS, Goldstein LS (1995) DNA binding and meiotic chromosomal localization of the Drosophila nod kinesin-like protein. Cell 81:129–138PubMedGoogle Scholar
  5. Ando S, Yang H, Nozaki N, Okazaki T, Yoda K (2002) CENP-A,-B, and-C chromatin complex that contains the I-type alpha-satellite array constitutes the prekinetochore in HeLa cells. Mol Cell Biol 22:2229–2241PubMedGoogle Scholar
  6. Antonio C, Ferby I, Wilhelm H, Jones M, Karsenti E, Nebreda AR, Vernos I (2000) Xkid, a chromokinesin required for chromosome alignment on the metaphase plate. Cell 102:425–435PubMedGoogle Scholar
  7. Ault JG, Nicklas RB (1989) Tension, microtubule rearrangements, and the proper distribution of chromosomes in mitosis. Chromosoma 98:33–39PubMedGoogle Scholar
  8. Babu JR, Jeganathan KB, Baker DJ, Wu X, Kang-Decker N, van Deursen JM (2003) Rael is an essential mitotic checkpoint regulator that cooperates with Bub3 to prevent chromosome missegregation. J Cell Biol 160:341–353PubMedGoogle Scholar
  9. Basu J, Bousbaa H, Logarinho E, Li Z, Williams BC, Lopes C, Sunkel CE, Goldberg ML (1999) Mutations in the essential spindle checkpoint bubl cause chromosome missegregation and fail to block apoptosis in Drosophila. J Cell Biol 46:13–28Google Scholar
  10. Barry AE, Howman EV, Cancilla MR, Saffery R, Choo KH (1999) Sequence analysis of an 80 kb human neocentromere. Hum Mol Genet 8:217–227PubMedGoogle Scholar
  11. Basto R, Gomes R, Karess R (2000) Rough Deal and ZW10 are required for the Metaphase checkpoint in Drosophila. Nat Cell Biol 2:939–943PubMedGoogle Scholar
  12. Bernard P, Maure JF, Partridge JF, Genier S, Javerzat JP, Allshire RC (2001) Requirement of heterochromatin for cohesion at centromeres. Science 294:2539–2542PubMedGoogle Scholar
  13. Biggins S, Severin FF, Bhalla N, Sassoon I, Hyman AA, Murray AW (1999) The conserved protein kinase Ipl1 regulates microtubule binding to kinetochores in budding yeast. Genes Dev 13:532–544PubMedGoogle Scholar
  14. Blower MD, Sullivan BA, Karpen GH (2002) Conserved organization of centromeric chromatin in flies and humans. Dev Cell 2:319–330PubMedGoogle Scholar
  15. Bolton MA, Lan W, Powers SE, McCleland ML, Kuang J, Stukenberg PT (2002) Aurora B kinase exists in a complex with survivin and INCENP and its kinase activity is stimulated by survivin binding and phosphorylation. Mol Biol Cell 13:3064–3077PubMedGoogle Scholar
  16. Cahill DP, Lengauer C, Yu J, Riggins GJ, Willson JK, Markowitz SD, Kinzler KW, Vogelstein B (1998) Mutations of mitotic checkpoint genes in human cancers. Nature 392:300–303PubMedGoogle Scholar
  17. Chan GK, Jablonski SA, Sudakin V, Hittle JC, Yen TJ (1999) Human BUBR1 is a mitotic checkpoint kinase that monitors CENP-E functions at kinetochores and binds the cyclosome/APC. J Cell Biol 146:941–954PubMedGoogle Scholar
  18. Chan GK, Jablonski SA, Starr DA, Goldberg ML, Yen TJ (2000) Human Zw10 and ROD are mitotic checkpoint proteins that bind to kinetochores. Nat Cell Biol 2:944–947PubMedGoogle Scholar
  19. Cheeseman IM, Brew C, Wolyniak M, Desai A, Anderson S, Muster N, Yates JR, Huffaker TC, Drubin DG, Barnes G (2001) Implication of a novel multiprotein Damlp complex in outer kinetochore function. J Cell Biol 155:1137–1145PubMedGoogle Scholar
  20. Cheeseman IM, Anderson S, Jwa M, Green EM, Kang J, Yates JR, Chan CS, Drubin DG, Barnes G (2002a) Phospho-regulation of kinetochore-microtubule attachments by the aurora kinase ipllp. Cell 111:163–172PubMedGoogle Scholar
  21. Cheeseman IM, Drubin DG, Barnes G (2002b) Simple centromere, complex kinetochore: linking spindle microtubules and centromeric DNA in budding yeast. J Cell Biol 157:199–203PubMedGoogle Scholar
  22. Chen RH, Waters JC, Salmon ED, Murray AW (1996) Association of spindle assembly checkpoint component XMAD2 with unattached kinetochores. Science 274:242–246PubMedGoogle Scholar
  23. Chen RH, Shevchenko A, Mann M, Murray AW (1998) Spindle checkpoint protein Xmadl recruits Xmad2 to unattached kinetochores. J Cell Biol 143:283–295PubMedGoogle Scholar
  24. Clarke L (1998) Centromeres: proteins, protein complexes, and repeated domains at centromeres of simple eukaryotes. Curr Opin Genet Dev 8:212–218PubMedGoogle Scholar
  25. Cohen-Fix O, Peters JM, Kirschner MW, Koshland D (1996) Anaphase initiation in Saccharomyces cerevisiae is controlled by the APC-dependent degradation of the anaphase inhibitor Pdslp. Genes Dev 10:3081–3093PubMedGoogle Scholar
  26. Dawson IA, Roth S, Akam M, Artavanis-Tsakonas S (1993) Mutations of the fizzy locus cause metaphase arrest in Drosophila melanogaster embryos. Development 117:359–376PubMedGoogle Scholar
  27. Desai A, Maddox PS, Mitchison TJ, Salmon ED (1998) Anaphase A chromosome movement and poleward spindle microtubule flux occur at similar rates in Xenopus extract spindles. J Cell Biol 141:703–713PubMedGoogle Scholar
  28. Desai A, Verma S, Mitchison TJ, Walczak CE (1999) Kin I kinesins are microtubule-destabilizing enzymes. Cell 96:69–78PubMedGoogle Scholar
  29. Dobles M, Liberal V, Scott ML, Benezra R, Sorger PK (2000) Chromosome missegregation and apoptosis in mice lacking the mitotic checkpoint Mad2. Cell 101:635–645PubMedGoogle Scholar
  30. Dou Z, Sawagechi A, Zhang J, Luo H, Brako L, Yao XB (2003) Dynamic distribution of TTK in HeLa cells: insights from an ultrastructural study. Cell Res 13:443–449PubMedGoogle Scholar
  31. Ekwall K, Olsson T, Turner BM, Cranston G, Allshire RC (1997) Transient inhibition of histone deacetylation alters the structural and functional imprint at fission yeast centromeres. Cell 91:1021–1032PubMedGoogle Scholar
  32. Fang G, Yu H, Kirschner MW (1998) The checkpoint protein MAD2 and the mitotic regulator CDC20 form a ternary complex with the anaphase-promoting complex to control anaphase initiation. Genes Dev 12:1871–1883PubMedGoogle Scholar
  33. Fisk HA, Mattison CP, Winey M (2003) Human Mpsl protein kinase is required for centrosome duplication and normal mitotic progression. Proc Natl Acad Sci USA 100:14875–14880PubMedGoogle Scholar
  34. Fraschini R, Beretta A, Sironi L, Musacchio A, Lucchini G, Piatti S (2001) Bub3 interaction with Mad2, Mad3 and Cdc20 is mediated by WD40 repeats and does not require intact kinetochores. EMBO J 20:6648–6659PubMedGoogle Scholar
  35. Funabiki H, Murray AW (2000) The Xenopus chromokinesin Xkid is essential for metaphase chromosome alignment and must be degraded to allow anaphase chromosome movement. Cell 102:411–424PubMedGoogle Scholar
  36. Gardner GD, Poddar A, Yellman C, Tavormina PA, Monteagudo MC, Burke DJ (2001) The spindle checkpoint of the yeast Saccharomyces cerevisiae requires kinetochore function and maps to the CBF3 domain. Genetics 157:1493–1502PubMedGoogle Scholar
  37. Gorbsky GJ, Sammak PJ, Borisy GG (1987) Chromosomes move poleward in anaphase along stationary microtubules that coordinately disassemble from their kinetochore ends. J Cell Biol 104:9–18PubMedGoogle Scholar
  38. Gorbsky GJ, Chen RH, Murray AW (1998) Micro injection of antibody to Mad2 protein into mammalian cells in mitosis induces premature anaphase. J Cell Biol 141:1193–1205PubMedGoogle Scholar
  39. Goshima G, Saitoh S, Yanagida M (1999) Proper metaphase spindle length is determined by centromere proteins Mis12 and Mis6 required for faithful chromosome segregation. Genes Dev 13:1664–1677PubMedGoogle Scholar
  40. Hardwick KG, Johnston RC, Smith DL, Murray AW (2000) MAD3 encodes a novel component of the spindle checkpoint which interacts with Bub3p, Cdc20p, and Mad2p. J Cell Biol 148:871–882PubMedGoogle Scholar
  41. Harrington JA, Van Bokkelen G, Mays RW, Gustashaw K, Willard HF (1997) Formation of de novo centromeres and construction of first-generation human artificial microchromosomes. Nat Genet 15:345–355PubMedGoogle Scholar
  42. Hartwell LH, Kastan MB (1994) Cell cycle control and cancer. Science 266:1821–1828PubMedGoogle Scholar
  43. Hays TS, Wise D, Salmon ED (1982) Traction force on a kinetochore at metaphase acts as a linear function of kinetochore fiber length. J Cell Biol 93:374–389PubMedGoogle Scholar
  44. He D, Zeng C, Woods K, Zhong L, Turner D, Busch RK, Brinkley BR, Busch H (1998) Cenp-g: a new centromeric protein that is associated with the alpha-1 satellite DNA subfamily. Chromosoma 107:189–197PubMedGoogle Scholar
  45. He X, Asthana S, Sorger PK (2000) Transient sister chromatid separation and elastic deformation of chromosomes during mitosis in budding yeast. Cell 101:763–775PubMedGoogle Scholar
  46. Hemmerich P, Stoyan T, Wieland G, Koch M, Lechner J, Diekmann S (2000) Interaction of yeast kinetochore proteins with centromere-protein/transcription factor Cbfl. Proc Natl Acad Sci USA 97:12583–12588PubMedGoogle Scholar
  47. Henikoff S, Ahmad K, Malik HS (2001) The centromere paradox: stable inheritance with rapidly evolving DNA. Science 293:1098–1102PubMedGoogle Scholar
  48. Hirano T (2000) Chromosome cohesion, condensation, and separation. Ann Rev Biochem 69:115–144PubMedGoogle Scholar
  49. Howell BJ, Hoffman DB, Fang G, Murray AW, Salmon ED (2000) Visualization of mad2 dynamics at kinetochores, along spindles fibers, and at spindle poles in living cells. J Cell Biol 150:1233–1250PubMedGoogle Scholar
  50. Howell BJ, McEwen BF, Canman JC, Hoffman DB, Farrar EM, Rieder CL, Salmon ED (2001) Cytoplasmic dynein/dynactin drives kinetochore protein transport to the spindle poles and has a role in mitotic spindle checkpoint inactivation. J Cell Biol 155:1159–1172PubMedGoogle Scholar
  51. Howman EV, Fowler KJ, Newson AJ, Redward S, MacDonald AC, Kalitsis P, Choo KH (2000) Early disruption of centromeric chromatin organization in centromere protein A (Cenpa) null mice. Proc Natl Acad Sci USA 97:1148–1153PubMedGoogle Scholar
  52. Hoyt MA, Totis L, Roberts BT (1991) S. cerevisiae genes required for cell cycle arrest in response to loss of microtubule function. Cell 66:507–517PubMedGoogle Scholar
  53. Hudson DF, Fowler KJ, Earle E, Saffery R, Kalitsis P, Trowell H, Hill J, Wreford NG, de Kretser DM, Cancilla MR et al. (1998) Centromere protein B null mice are mitotically and meiotically normal but have lower body and testis weights. J Cell Biol 141:309–319PubMedGoogle Scholar
  54. Hyman AA, Mitchison TJ (1991) Two different microtubule-based motor activities with opposite polarities in kinetochores. Nature 351:206–211PubMedGoogle Scholar
  55. Ikeno M, Grimes B, Okazaki T, Nakano M, Saitoh K, Hoshino H, McGill NI, Cooke H, Masumoto H (1998) Construction of YAC-based mammalian artificial chromosomes. Nat Biotechnol 16:431–439PubMedGoogle Scholar
  56. Janke C, Ortiz J, Lechner J, Shevchenko A, Shevchenko A, Magiera MM, Schramm C, Schiebel E (2001) The budding yeast proteins Spc24p and Spc25p interact with Ndc80p and Nuf2p at the kinetochore and are important for kinetochore clustering and checkpoint control. EMBO J 20:777–791PubMedGoogle Scholar
  57. Janke C, Ortiz J, Tanaka TU, Lechner J, Schiebel E (2002) Four new subunits of the Daml-Duol complex reveal novel functions in sister kinetochore biorientation. EMBO J 21:181–193PubMedGoogle Scholar
  58. Kalitsis P, Earle E, Fowler KJ, Choo KH (2000) Bub3 gene disruption in mice reveals essential mitotic spindle checkpoint function during early embryogenesis. Genes Dev 14:2277–2282PubMedGoogle Scholar
  59. Kallio M, Weinstein J, Daum JR, Burke DJ, Gorbsky GJ (1998) Mammalian p55CDC mediates association of the spindle checkpoint protein Mad2 with the cyclosome/anaphase-promoting complex, and is involved in regulating anaphase onset and late mitotic events. J Cell Biol 141:1393–1406PubMedGoogle Scholar
  60. Kallio MJ, Beardmore VA, Weinstein J, Gorbsky GJ (2002) Rapid microtubule-independent dynamics of Cdc20 at kinetochores and centrosomes in mammalian cells. J Cell Biol 158:841–847PubMedGoogle Scholar
  61. Kaplan KB, Burds AA, Swedlow JR, Bekir SS, Sorger PK, Nathke IS (2001) A role for the Adenomatous Polyposis Coli protein in chromosome segregation. Nat Cell Biol 3:429–432PubMedGoogle Scholar
  62. Ke YW, Dou Z, Zhang J, Yao XB (2003) Function and regulation of Aurora/Ipllp kinase family in cell division. Cell Res 13:69–81PubMedGoogle Scholar
  63. Keith KC, Fitzgerald-Hayes M (2000) CSE4 genetically interacts with the Sac-charomyces cerevisiae centromere DNA elements CDE I and CDE II but not CDE III. Implications for the path of the centromere DNA around a cse4p variant nucleosome. Genetics 156:973–981PubMedGoogle Scholar
  64. Khodjakov A, Rieder CL (1996) Kinetochores moving away from their associated pole do not exert a significant pushing force on the chromosome. J Cell Biol 135:315–327PubMedGoogle Scholar
  65. Khodjakov A, Cole RW, McEwen BF, Buttle KF, Rieder CL (1997) Chromosome fragments possessing only one kinetochore can congress to the spindle equator. J Cell Biol 136:229–240PubMedGoogle Scholar
  66. Kim SH, Lin DP, Matsumoto S, Kitazono A, Matsumoto T (1998) Fission yeast Slpl: an effector of the Mad2-dependent spindle checkpoint. Science 279:1045–1047PubMedGoogle Scholar
  67. Kitajima TS, Kawashima SA, Watanabe Y (2004) The conserved kinetochore protein shugoshin protects centromeric cohesion during meiosis. Nature 427:510–7PubMedGoogle Scholar
  68. Lachner M, O’Carroll D, Rea S, Mechtler K, Jenuwein T (2001) Methylation of histone H3 lysine 9 creates a binding site for HP1 proteins. Nature 410:116–120PubMedGoogle Scholar
  69. Laloraya S, Guacci V, Koshland D (2000) Chromosomal addresses of the cohesin component Mcdlp. J Cell Biol 151:1047–1056PubMedGoogle Scholar
  70. Lan W, Zhang X, Kline-Smith SL, Rosasco SE, Barrett-Wilt GA, Shabanowitz J, Hunt DF, Walczak CE, Stukenberg PT (2004) Aurora B phosphorylates centromeric MCAK and regulates its localization and micro tubule depolymerization activity. Curr Biol 14:273–86PubMedGoogle Scholar
  71. Levesque AA, Compton DA (2001) The chromokinesin Kid is necessary for chromosome arm orientation and oscillation, but not congression, on mitotic spindles. J Cell Biol 154:1135–1146PubMedGoogle Scholar
  72. Li Y, Benezra R (1996) Identification of a human mitotic checkpoint gene: hsMAD2. Science 274:246–248PubMedGoogle Scholar
  73. Li R, Murray AW (1991) Feedback control of mitosis in budding yeast. Cell 66:519–531PubMedGoogle Scholar
  74. Li X, Nicklas RB (1995) Mitotic forces control a cell-cycle checkpoint. Nature 373:630–632PubMedGoogle Scholar
  75. Li Y, Bachant J, Alcasabas AA, Wang Y, Qin J, Elledge SJ (2002) The mitotic spindle is required for loading of the DASH complex onto the kinetochore. Genes Dev 16:183–197PubMedGoogle Scholar
  76. Liu ST, Chan GK, Hittle JC, Fujii G, Lees E, Yen TJ (2003) Human MPS1 kinase is required for mitotic arrest induced by the loss of CENP-E from kinetochores. Mol Biol Cell 14:1638–1651PubMedGoogle Scholar
  77. Lou Y, Yao J, Zenreski A, Ahmed K, Wang H, Hu J, Wang Y, Yao X (2004) Nek2A interacts with Madl and possibly functions as a novel integrator of the spindle checkpoint signaling. J Biol Chem 279: 20049–20057PubMedGoogle Scholar
  78. Maddox P, Desai A, Oegema K, Mitchison TJ, Salmon ED (2002) Poleward microtubule flux is a major component of spindle dynamics and anaphase a in mitotic Drosophila embryos. Curr Biol 12:1670–1674PubMedGoogle Scholar
  79. Marston AL, Tham WH, Shah H, Amon A (2004) A genome-wide screen identifies genes required for centromeric cohesion. Science 303:1367–1370PubMedGoogle Scholar
  80. Martin-Lluesma S, Stucke VM, Nigg EA (2002) Role of hecl in spindle checkpoint signaling and kinetochore recruitment of madl/mad2. Science 297:2267–2270PubMedGoogle Scholar
  81. McEwen BF, Chan GKT, Zubrowski B, Savoian MS, Sauer MT, Yen TJ (2001) CENP-E is essential for reliable bioriented spindle attachment, but chromosome alignment can be achieved via redundant mechanisms in mammalian cells. Mol Biol Cell 12:2776–2789PubMedGoogle Scholar
  82. Mclntosh JR (1991) Structural and mechanical control of mitotic progression. Cold Spring Harb Symp Quant Biol 56:613–619Google Scholar
  83. Megee PC, Mistrot C, Guacci V, Koshland D (1999) The centromeric sister chromatid cohesion site directs Mcdlp binding to adjacent sequences. Mol Cell 4:445–450PubMedGoogle Scholar
  84. Meluh PB, Koshland D (1995) Evidence that the MIF2 gene of Saccharomyces cerevisiae encodes a centromere protein with homology to the mammalian centromere protein CENP-C. Mol Biol Cell 6:793–807PubMedGoogle Scholar
  85. Meluh PB, Yang P, Glowczewski L, Koshland D, Smith MM (1998) Cse4p is a component of the core centromere of Saccharomyces cerevisiae. Cell 94:607–613PubMedGoogle Scholar
  86. Michel LS, Liberal V, Chatterjee A, Kirchwegger R, Pasche B, Gerald W, Dobles M, Sorger PK, Murty VV, Benezra R (2001) Mad2 haplo-insufficiency causes premature anaphase and chromosome instability in mammalian cells. Nature 409:355–359PubMedGoogle Scholar
  87. Mitchison TJ, Salmon ED (1992) Poleward kinetochore fiber movement occurs during both metaphase and anaphase-A in newt lung cell mitosis. J Cell Biol 119:569–582PubMedGoogle Scholar
  88. Musacchio A, Hardwick KG (2002) The spindle checkpoint: structural insights into dynamic signalling. Nat Rev Mol Cell Biol 3:731–741PubMedGoogle Scholar
  89. Nicklas RB (1983) Measurements of the force produced by the mitotic spindle in anaphase. J Cell Biol 97:542–548PubMedGoogle Scholar
  90. Nicklas RB (1988) The forces that move chromosomes in mitosis. Annu Rev Bio-phys Biophys Chem 17:431–49Google Scholar
  91. Oegema K, Desai A, Rybina S, Kirkham M, Hyman AA (2001) Functional analysis of kinetochore assembly in Caenorhabditis elegans. J Cell Biol 153:1209–1226PubMedGoogle Scholar
  92. Ohzeki J, Nakano M, Okada T, Masumoto H (2002) CENP-B box is required for de novo centromere chromatin assembly on human alphoid DNA. J Cell Biol 159:765–775PubMedGoogle Scholar
  93. Ortiz J, Stemmann O, Rank S, Lechner J (1999) A putative protein complex consisting of Ctfl9, Mcm21, and Okpl represents a missing link in the budding yeast kinetochore. Genes Dev 13:1140–1155PubMedGoogle Scholar
  94. Ostergren G (1951) The mechanism of co-orientation in bivalents and multivalents. Hereditas 37:85–156Google Scholar
  95. Partridge JF, Borgstrom B, Allshire RC (2000) Distinct protein interaction domains and protein spreading in a complex centromere. Genes Dev 14:783–791PubMedGoogle Scholar
  96. Partridge J, Scott K, Bannister A, Kouzarides T, Allshire R (2002) cisacting DNA from fission yeast centromeres mediates histone H3 methylation and recruitment of silencing factors and cohesin to an ectopic site. Curr Biol 12:1652–1660PubMedGoogle Scholar
  97. Putkey FR, Cramer T, Morphew MK, Silk AD, Johnson RS, Mclntosh JR, Cleveland DW (2002) Unstable kinetochore-microtubule capture and chromosomal instability following deletion of CENP-E. Dev Cell 3:351–365PubMedGoogle Scholar
  98. Raff JW, Jeffers K, Huang JY (2002) The roles of Fzy/Cdc20 and Fzr/Cdh1 in regulating the destruction of cyclin B in space and time. J Cell Biol 157:1139–1149PubMedGoogle Scholar
  99. Richards EJ, Elgin SC (2002) Epigenetic codes for heterochromatin formation and silencing: rounding up the usual suspects. Cell 108:489–500PubMedGoogle Scholar
  100. Rieder CL (1981) The structure of the cold-stable kinetochore fiber in metaphase PtK1 cells. Chromosoma 84:145–158PubMedGoogle Scholar
  101. Rieder CL, Alexander SP (1990) Kinetochores are transported poleward along a single astral microtubule during chromosome attachment to the spindle in newt lung cells. J Cell Biol 110:81–95PubMedGoogle Scholar
  102. Rieder CL, Cole RW, Khodjakov A, Sluder G (1995) The checkpoint delaying anaphase in response to chromosome monoorientation is mediated by an inhibitory signal produced by unattached kinetochores. J Cell Biol 130:941–948PubMedGoogle Scholar
  103. Rieder CL, Khodjakov A, Paliulis LV, Fortier TM, Cole RW, Sluder G (1997) Mitosis in vertebrate somatic cells with two spindles: implications for the metaphase/anaphase transition checkpoint and cleavage. Proc Natl Acad Sci USA 94:5107–5112PubMedGoogle Scholar
  104. Roberts BT, Farr KA, Hoyt MA (1994) The Saccharomyces cerevisiae checkpoint gene BUB1 encodes a novel protein kinase. Mol Cell Biol 14:8282–8291PubMedGoogle Scholar
  105. Rogers SL, Rogers GC, Sharp DJ, Vale RD (2002) Drosophila EB1 is important for proper assembly, dynamics, and positioning of the mitotic spindle. J Cell Biol 158:873–884PubMedGoogle Scholar
  106. Rogers GC, Rogers SL, Schwimmer TA, Ems-McClung SC, Walczak CE, Vale RD, Scholey JM, Sharp DJ (2004) Two mitotic kinesins cooperate to drive sister chromatid separation during anaphase. Nature 427:364–370PubMedGoogle Scholar
  107. Russell ID, Grancell AS, Sorger PK (1999) The unstable F-box protein p58-Ctf13 forms the structural core of the CBF3 kinetochore complex. J Cell Biol 145:933–950PubMedGoogle Scholar
  108. Savoian MS, Goldberg ML, Rieder CL (2000) The rate of chromosome poleward motion is attenuated in Drosophila zw10 and rod mutants. Nat Cell Biol 2:948–952PubMedGoogle Scholar
  109. Scholey JM, Brust-Mascher I, Mogilner A (2003) Cell division. Nature 422:746–752PubMedGoogle Scholar
  110. Schueler MG, Higgins AW, Rudd MK, Gustashaw K, Willard HF (2001) Genomic and genetic definition of a functional human centromere. Science 294:109–115PubMedGoogle Scholar
  111. Sharp DJ, Rogers GC, Scholey JM (2000) Cytoplasmic dynein is required for poleward chromosome movement during mitosis in Drosophila embryos. Nat Cell Biol 2:922–930PubMedGoogle Scholar
  112. Shelby RD, Vafa O, Sullivan KF (1997) Assembly of CENP-A into centromeric chromatin requires a cooperative array of nucleosomal DNA contact sites. J Cell Biol 136:501–513PubMedGoogle Scholar
  113. Shelby RD, Monier K, Sullivan KF (2000) Chromatin assembly at kinetochores is uncoupled from DNA replication. J Cell Biol 151:1113–1118PubMedGoogle Scholar
  114. Shingyoji C, Higuchi H, Yoshimura M, Katayama E, Yanagida T (1998) Dynein arms are oscillating force generators. Nature 393:711–714PubMedGoogle Scholar
  115. Skibbens RV, Skeen VP, Salmon ED (1993) Directional instability of kinetochore motility during chromosome congression and segregation in mitotic newt lung cells: a push-pull mechanism. J Cell Biol 122:859–875PubMedGoogle Scholar
  116. Skoufias DA, Andreassen PR, Lacroix FB, Wilson L, Margolis RL (2001) Mammalian mad2 and bub1/bubR1 recognize distinct spindle-attachment and kinetochore-tension checkpoints. Proc Natl Acad Sci USA 98:4492–1497PubMedGoogle Scholar
  117. Smith MM (2002) Centromeres and variant histones: what, where, when and why? Curr Opin Cell Biol 14:279–285PubMedGoogle Scholar
  118. Stoler S, Keith KC, Curnick KE, Fitzgerald-Hayes M (1995) A mutation in CSE4, an essential gene encoding a novel chromatin-associated protein in yeast, causes chromosome nondisjunction and cell cycle arrest at mitosis. Genes Dev 9:573–586PubMedGoogle Scholar
  119. Su LK, Burrell M, Hill DE, Gyuris J, Brent R, Wiltshire R, Trent J, Vogelstein B, Kinzler KW (1995) APC binds to the novel protein EB1. Cancer Res 55:2972–2977PubMedGoogle Scholar
  120. Sudakin V, Chan GK, Yen TJ (2001) Checkpoint inhibition of the APC/C in HeLa cells is mediated by a complex of BUBR1, BUB3, CDC20, and MAD2. J Cell Biol 154:925–936PubMedGoogle Scholar
  121. Sullivan B, Karpen G (2001) Centromere identity in Drosophila is not determined in vivo by replication timing. J Cell Biol 154:683–690PubMedGoogle Scholar
  122. Sullivan BA, Willard HF (1998) Stable dicentric X chromosomes with two functional centromeres. Nat Genet 20:227–228PubMedGoogle Scholar
  123. Sullivan BA, Blower MD, Karpen GH (2001) Determining centromere identity: cyclical stories and forking paths. Nat Rev Genet 2:584–596PubMedGoogle Scholar
  124. Sun X, Wahlstrom J, Karpen GH (1997) Molecular structure of a functional Drosophila centromere. Cell 91:1007–1019PubMedGoogle Scholar
  125. Takahashi K, Chen ES, Yanagida M (2000) Requirement of Mis6 centromere connector for localizing a CENP-A-like protein in fission yeast. Science 288:2215–2219PubMedGoogle Scholar
  126. Takenaka K, Moriguchi T, Nishida E (1998) Activation of the protein kinase p38 in the spindle assembly checkpoint and mitotic arrest. Science 280:599–602PubMedGoogle Scholar
  127. Tanaka T, Cosma MP, Wirth K, Nasmyth K (1999) Identification of cohesin association sites at centromeres and along chromosome arms. Cell 98:847–858PubMedGoogle Scholar
  128. Tanaka TU, Rachidi N, Janke C, Pereira G, Galova M, Schiebel E, Stark MJ, Nasmyth K (2002) Evidence that the Ipl1-Sli15 (Aurora kinase-INCENP) complex promotes chromosome bi-orientation by altering kinetochore-spindle pole connections. Cell 108:317–329PubMedGoogle Scholar
  129. Tang Z, Bharadwaj R, Li B, Yu H (2001) Mad2-independent inhibition of APCcdc20 by the mitotic checkpoint protein Bubr1. Dev Cell 1:227–237PubMedGoogle Scholar
  130. Taylor SS, McKeon F (1997) Kinetochore localization of murine Bub1 is required for normal mitotic timing and checkpoint response to spindle damage. Cell 89:727–735PubMedGoogle Scholar
  131. Taylor SS, Ha E, McKeon F (1998) The human homologue of Bub3 is required for kinetochore localization of Bub1 and a Mad3/Bub1-related protein kinase. J Cell Biol 142:1–11PubMedGoogle Scholar
  132. Tirnauer JS, Canman JC, Salmon ED, Mitchison TJ (2002) EB1 targets to kinetochores with attached, polymerizing microtubules. Mol Biol Cell 13:4308–4316PubMedGoogle Scholar
  133. Tugendreich S, Tomkiel J, Earnshaw W, Hieter P (1995) CDC27Hs colocalizes with CDC16Hs to the centrosome and mitotic spindle and is essential for the metaphase to anaphase transition. Cell 81:261–268PubMedGoogle Scholar
  134. Tyler-Smith C, Oakey RJ, Larin Z, Fisher RB, Crocker M, Affara NA, Ferguson-Smith MA, Muenke M, Zuffardi O, Jobling MA (1993) Localization of DNA sequences required for human centromere function through an analysis of rearranged Y chromosomes. Nat Genet 5:368–375PubMedGoogle Scholar
  135. Tyler-Smith C, Gimelli G, Giglio S, Floridia G, Pandya A, Terzoli G, Warburton PE, Earnshaw WC, Zuffardi O (1999) Transmission of a fully functional human neocentromere through three generations. Am J Hum Genet 64:1440–1444PubMedGoogle Scholar
  136. Vafa O, Sullivan KF (1997) Chromatin containing CENP-A and alpha-satellite DNA is a major component of the inner kinetochore plate. Curr Biol 7:897–900PubMedGoogle Scholar
  137. Volpe TA, Kidner C, Hall IM, Teng G, Grewal SI, Martienssen RA (2002) Regulation of heterochromatic silencing and histone H3 lysine-9 methylation by RNAi. Science 297:1833–1837PubMedGoogle Scholar
  138. Walczak CE, Mitchison TJ, Desai A (1996) XKCM1: a xenopus kinesin-related protein that regulates microtubule dynamics during mitotic spindle assembly. Cell 84:37–47PubMedGoogle Scholar
  139. Walters JC, Mitchison TJ, Rieder CL, Salmon ED (1996) The kinetochore microtubule minus-end disassembly associated with poleward flux produces a force that can do work. Mol Biol Cell 7:1547–1558Google Scholar
  140. Waters JC, Chen RH, Murray AW, Salmon ED (1998) Localization of Mad2 to kinetochores depends on microtubule attachment, not tension. J Cell Biol 141:1181–1191PubMedGoogle Scholar
  141. Weaver BA, Bonday ZQ, Putkey FR, Kops GJ, Silk AD, Cleveland DW (2003) Centromere-associated protein-E is essential for the mammalian mitotic checkpoint to prevent aneuploidy due to single chromosome loss. J Cell Biol 162:551–563PubMedGoogle Scholar
  142. Weiss E, Winey M (1996) The Saccharomyces cerevisiae spindle pole body duplication gene MPS1 is part of a mitotic checkpoint. J Cell Biol 132:111–123PubMedGoogle Scholar
  143. Wigge PA, Kilmartin JV (2001) The Ndc80p complex from Saccharomyces cerevisiae contains conserved centromere components and has a function in chromosome segregation. J Cell Biol 152:349–360PubMedGoogle Scholar
  144. Williams BC, Gatti M, Goldberg ML (1996) Bipolar spindle attachments affect redistributions of ZW10, aDrosophila centromere/kinetochore component required for accurate chromosome segregation. J Cell Bioll 34:1127–1140Google Scholar
  145. Wordeman, L and Mitchison, TJ (1995) Identification and partial characterization of mitotic centromere-associated kinesin, a kinesin-related protein that associates with centromeres during mitosis. J Cell Biol 128:95–104PubMedGoogle Scholar
  146. Yao X, Anderson K, Cleveland DW (1997) The microtubule-dependent motor centromere-associated protein E (CENP-E) is an integral component of kinetochore corona fibers that link centromeres to spindle microtubules. J Cell Biol 139:435–447PubMedGoogle Scholar
  147. Yao X, Abrieu A, Zheng Y, Sullivan KF, Cleveland DW (2000) CENP-E forms a link between attachment of spindle microtubules to kinetochores and the mitotic checkpoint. Nat Cell Biol 2:484–491PubMedGoogle Scholar
  148. Yeh E, Skibbens RV, Cheng JW, Salmon ED, Bloom K (1995) Spindle dynamics and cell cycle regulation of dynein in the budding yeast, Saccharomyces cerevisiae. J Cell Biol 130:687–700PubMedGoogle Scholar
  149. Yoda K, Ando S, Morishita S, Houmura K, Hashimoto K, Takeyasu K, Okazaki T (2000) Human centromere protein A (CENP-A) can replace histone H3 in nucleosome reconstitution in vitro. Proc Natl Acad Sci USA 97: 7266–7271PubMedGoogle Scholar
  150. Yu HG, Muszynski MG, Kelly Dawe R (1999) The maize homologue of the cell cycle checkpoint protein MAD2 reveals kinetochore substructure and contrasting mitotic and meiotic localization patterns. J Cell Biol 145:425–435PubMedGoogle Scholar
  151. Zou H, McGarry TJ, Bernal T, Kirschner MW (1999) Identification of a vertebrate sister-chromatid separation inhibitor involved in transformation and tumorigenesis. Science 285:418–422PubMedGoogle Scholar
  152. Zhou J, Panda D, Landen JW, Wilson L, Joshi HC (2002) Minor alteration of microtubule dynamics causes loss of tension across kinetochore pairs and activates the spindle checkpoint. J Biol Chem 277:17200–17208PubMedGoogle Scholar
  153. Zinkowski RP, Meyne J, Brinkley BR (1991) The centromere-kinetochore complex: a repeat subunit model. J Cell Biol 113:1091–1110PubMedGoogle Scholar
  154. Zumbrunn J, Inoshita K, Hyman AA, Nathke IS (2001) Binding of the Adenomatous Polyposis Coli protein to microtubules increases microtubules stability and is regulated by GSK3b phosphorylation. Curr Biol 11:44–49PubMedGoogle Scholar
  155. Zur A, Brandeis M (2001) Securin degradation is mediated by fzy and fzr, and is required for complete chromatid separation but not for cytokinesis. EMBO J 20:792–801PubMedGoogle Scholar

Copyright information

© Springer 2007

Authors and Affiliations

  • Yu Xue
    • 1
  • Chuanhai Fu
    • 1
  • Yong Miao
    • 1
  • Jianhui Yao
    • 1
  • Zhen Dou
    • 1
  • Jie Zhang
    • 1
  • Larry Brako
    • 2
  • Xuebiao Yao
    • 1
    • 2
  1. 1.Laboratory of Cell Dynamics, School of Life SciencesUniversity of Science & Technology of ChinaHefeiChina
  2. 2.Department of PhysiologyMorehouse School of MedicineAtlantaUSA

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