Advertisement

Chromosoma

, Volume 122, Issue 3, pp 135–158 | Cite as

Making an effective switch at the kinetochore by phosphorylation and dephosphorylation

  • Hironori FunabikiEmail author
  • David J. Wynne
Review Article

Abstract

The kinetochore, the proteinaceous structure on the mitotic centromere, functions as a mechanical latch that hooks onto microtubules to support directional movement of chromosomes. The structure also brings in a number of signaling molecules, such as kinases and phosphatases, which regulate microtubule dynamics and cell cycle progression. Erroneous microtubule attachment is destabilized by Aurora B-mediated phosphorylation of multiple microtubule-binding protein complexes at the kinetochore, such as the KMN network proteins and the Ska/Dam1 complex, while Plk-dependent phosphorylation of BubR1 stabilizes kinetochore–microtubule attachment by recruiting PP2A-B56. Spindle assembly checkpoint (SAC) signaling, which is activated by unattached kinetochores and inhibits the metaphase-to-anaphase transition, depends on kinetochore recruitment of the kinase Bub1 through Mps1-mediated phosphorylation of the kinetochore protein KNL1 (also known as Blinkin in mammals, Spc105 in budding yeast, and Spc7 in fission yeast). Recruitment of protein phosphatase 1 to KNL1 is necessary to silence the SAC upon bioriented microtubule attachment. One of the key unsolved questions in the mitosis field is how a mechanical change at the kinetochore upon microtubule attachment is converted to these and other chemical signals that control microtubule attachment and the SAC. Rapid progress in the field is revealing the existence of an intricate signaling network created right on the kinetochore. Here we review the current understanding of phosphorylation-mediated regulation of kinetochore functions and discuss how this signaling network generates an accurate switch that turns on and off the signaling output in response to kinetochore–microtubule attachment.

Keywords

Mitosis Cell cycle Chromosome segregation Kinetochore Spindle Checkpoint Kinase Phosphatase Feedback 

Notes

Acknowledgments

HF is supported by a National Institutes of Health (NIH) grant (R01GM075249), and DW is supported by a NIH Ruth L. Kirschstein National Research Service Award Postdoctoral Fellowship (1F32GM103147). We thank Sahand Jamal Rahi for critical comments on the manuscript.

Supplementary material

412_2013_401_MOESM1_ESM.doc (457 kb)
ESM 1 (DOC 457 kb)

References

  1. Abrieu A, Magnaghi-Jaulin L, Kahana JA, Peter M, Castro A, Vigneron S, Lorca T, Cleveland DW, Labbe JC (2001) Mps1 is a kinetochore-associated kinase essential for the vertebrate mitotic checkpoint. Cell 106:83–93PubMedCrossRefGoogle Scholar
  2. Ahonen LJ, Kallio MJ, Daum JR, Bolton M, Manke IA, Yaffe MB, Stukenberg PT, Gorbsky GJ (2005) Polo-like kinase 1 creates the tension-sensing 3F3/2 phosphoepitope and modulates the association of spindle-checkpoint proteins at kinetochores. Curr Biol 15:1078–1089PubMedCrossRefGoogle Scholar
  3. Akiyoshi B, Nelson CR, Ranish JA, Biggins S (2009a) Analysis of Ipl1-mediated phosphorylation of the Ndc80 kinetochore protein in Saccharomyces cerevisiae. Genetics 183:1591–1595PubMedCrossRefGoogle Scholar
  4. Akiyoshi B, Nelson CR, Ranish JA, Biggins S (2009b) Quantitative proteomic analysis of purified yeast kinetochores identifies a PP1 regulatory subunit. Genes Dev 23:2887–2899PubMedCrossRefGoogle Scholar
  5. Akiyoshi B, Sarangapani KK, Powers AF, Nelson CR, Reichow SL, Arellano-Santoyo H, Gonen T, Ranish JA, Asbury CL, Biggins S (2010) Tension directly stabilizes reconstituted kinetochore–microtubule attachments. Nature 468:576–579PubMedCrossRefGoogle Scholar
  6. Alexander J, Lim D, Joughin BA, Hegemann B, Hutchins JR, Ehrenberger T, Ivins F, Sessa F, Hudecz O, Nigg EA, Fry AM, Musacchio A, Stukenberg PT, Mechtler K, Peters JM, Smerdon SJ, Yaffe MB (2011) Spatial exclusivity combined with positive and negative selection of phosphorylation motifs is the basis for context-dependent mitotic signaling. Sci Signal 4:ra42PubMedCrossRefGoogle Scholar
  7. Alushin GM, Ramey VH, Pasqualato S, Ball DA, Grigorieff N, Musacchio A, Nogales E (2010) The Ndc80 kinetochore complex forms oligomeric arrays along microtubules. Nature 467:805–810PubMedCrossRefGoogle Scholar
  8. 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 6:253–268PubMedCrossRefGoogle Scholar
  9. Bentley AM, Normand G, Hoyt J, King RW (2007) Distinct sequence elements of cyclin B1 promote localization to chromatin, centrosomes, and kinetochores during mitosis. Mol Biol Cell 18:4847–4858PubMedCrossRefGoogle Scholar
  10. Bernard P, Maure JF, Javerzat JP (2001) Fission yeast Bub1 is essential in setting up the meiotic pattern of chromosome segregation. Nat Cell Biol 3:522–526PubMedCrossRefGoogle Scholar
  11. Biggins S, Murray AW (2001) The budding yeast protein kinase Ipl1/Aurora allows the absence of tension to activate the spindle checkpoint. Genes Dev 15:3118–3129PubMedCrossRefGoogle Scholar
  12. Booher R, Beach D (1989) Involvement of a type 1 protein phosphatase encoded by bws1 + in fission yeast mitotic control. Cell 57:1009–1016PubMedCrossRefGoogle Scholar
  13. Boyarchuk Y, Salic A, Dasso M, Arnaoutov A (2007) Bub1 is essential for assembly of the functional inner centromere. J Cell Biol 176:919–928PubMedCrossRefGoogle Scholar
  14. Burton JL, Solomon MJ (2007) Mad3p, a pseudosubstrate inhibitor of APCCdc20 in the spindle assembly checkpoint. Genes Dev 21:655–667PubMedCrossRefGoogle Scholar
  15. Buttrick GJ, Lancaster TC, Meadows JC, Millar JB (2012) Plo1 phosphorylates Dam1 to promote chromosome bi-orientation in fission yeast. J Cell Sci 125:1645–1651PubMedCrossRefGoogle Scholar
  16. Cai S, O'Connell CB, Khodjakov A, Walczak CE (2009) Chromosome congression in the absence of kinetochore fibres. Nat Cell Biol 11:832–838PubMedCrossRefGoogle Scholar
  17. Carmena M, Pinson X, Platani M, Salloum Z, Xu Z, Clark A, Macisaac F, Ogawa H, Eggert U, Glover DM, Archambault V, Earnshaw WC (2012a) The chromosomal passenger complex activates Polo kinase at centromeres. PLoS Biol 10:e1001250PubMedCrossRefGoogle Scholar
  18. Carmena M, Wheelock M, Funabiki H, Earnshaw WC (2012b) The chromosomal passenger complex (CPC): from easy rider to the godfather of mitosis. Nat Rev Mol Cell Biol 13(12):789–803PubMedCrossRefGoogle Scholar
  19. Ceulemans H, Vulsteke V, De Maeyer M, Tatchell K, Stalmans W, Bollen M (2002) Binding of the concave surface of the Sds22 superhelix to the alpha 4/alpha 5/alpha 6-triangle of protein phosphatase-1. J Biol Chem 277:47331–47337PubMedCrossRefGoogle Scholar
  20. Chan GK, Schaar BT, Yen TJ (1998) Characterization of the kinetochore binding domain of CENP-E reveals interactions with the kinetochore proteins CENP-F and hBUBR1. J Cell Biol 143:49–63PubMedCrossRefGoogle Scholar
  21. 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 146:941–954PubMedCrossRefGoogle Scholar
  22. Chan YW, Jeyaprakash AA, Nigg EA, Santamaria A (2012) Aurora B controls kinetochore–microtubule attachments by inhibiting Ska complex–KMN network interaction. J Cell Biol 196:563–571PubMedCrossRefGoogle Scholar
  23. Chao WC, Kulkarni K, Zhang Z, Kong EH, Barford D (2012) Structure of the mitotic checkpoint complex. Nature 484:208–213PubMedCrossRefGoogle Scholar
  24. Cheeseman IM, Desai A (2008) Molecular architecture of the kinetochore–microtubule interface. Nat Rev Mol Cell Biol 9:33–46PubMedCrossRefGoogle Scholar
  25. Cheeseman IM, Anderson S, Jwa M, Green EM, Js K, Yates JR, Chan CSM, Drubin DG, Barnes G (2002) Phospho-regulation of kinetochore–microtubule attachments by the Aurora kinase Ipl1p. Cell 111:163–172PubMedCrossRefGoogle Scholar
  26. Cheeseman IM, Niessen S, Anderson S, Hyndman F, Yates JR 3rd, Oegema K, Desai A (2004) A conserved protein network controls assembly of the outer kinetochore and its ability to sustain tension. Genes Dev 18:2255–2268PubMedCrossRefGoogle Scholar
  27. Cheeseman IM, Chappie JS, Wilson-Kubalek EM, Desai A (2006) The conserved KMN network constitutes the core microtubule-binding site of the kinetochore. Cell 127:983–997PubMedCrossRefGoogle Scholar
  28. Chen RH (2002) BubR1 is essential for kinetochore localization of other spindle checkpoint proteins and its phosphorylation requires Mad1. J Cell Biol 158:487–496PubMedCrossRefGoogle Scholar
  29. Chen RH (2004) Phosphorylation and activation of Bub1 on unattached chromosomes facilitate the spindle checkpoint. EMBO J 23:3113–3121PubMedCrossRefGoogle Scholar
  30. Chen R-H, Waters JC, Salmon ED, Murray AW (1996) Association of spindle assembly checkpoint component XMAD2 with unattached kinetochores. Science 274:242–246PubMedCrossRefGoogle Scholar
  31. Chen R-H, Shevchenko A, Mann M, Murray AW (1998) Metaphase arrest induced by an excess of the spindle checkpoint protein Xmad2 is independent of Xmad1. J Cell Biol 143:283–295PubMedCrossRefGoogle Scholar
  32. Cheng L, Zhang J, Ahmad S, Rozier L, Yu H, Deng H, Mao Y (2011) Aurora B regulates formin mDia3 in achieving metaphase chromosome alignment. Dev Cell 20:342–352PubMedCrossRefGoogle Scholar
  33. Choi E, Choe H, Min J, Choi JY, Kim J, Lee H (2009) BubR1 acetylation at prometaphase is required for modulating APC/C activity and timing of mitosis. EMBO J 28:2077–2089PubMedCrossRefGoogle Scholar
  34. Chung E, Chen RH (2003) Phosphorylation of Cdc20 is required for its inhibition by the spindle checkpoint. Nat Cell Biol 5:748–753PubMedCrossRefGoogle Scholar
  35. Ciferri C, Pasqualato S, Screpanti E, Varetti G, Santaguida S, Dos Reis G, Maiolica A, Polka J, De Luca JG, De Wulf P, Salek M, Rappsilber J, Moores CA, Salmon ED, Musacchio A (2008) Implications for kinetochore–microtubule attachment from the structure of an engineered Ndc80 complex. Cell 133:427–439PubMedCrossRefGoogle Scholar
  36. Cimini D, Wan X, Hirel CB, Salmon ED (2006) Aurora kinase promotes turnover of kinetochore microtubules to reduce chromosome segregation errors. Curr Biol 16:1711–1718PubMedCrossRefGoogle Scholar
  37. Clute P, Pines J (1999) Temporal and spatial control of cyclin B1 destruction in metaphase. Nat Cell Biol 1:82–87PubMedCrossRefGoogle Scholar
  38. Coffman VC, Wu P, Parthun MR, Wu JQ (2011) CENP-A exceeds microtubule attachment sites in centromere clusters of both budding and fission yeast. J Cell Biol 195:563–572PubMedCrossRefGoogle Scholar
  39. D'Angiolella V, Mari C, Nocera D, Rametti L, Grieco D (2003) The spindle checkpoint requires cyclin-dependent kinase activity. Genes Dev 17:2520–2525PubMedCrossRefGoogle Scholar
  40. Dawlaty MM, Malureanu L, Jeganathan KB, Kao E, Sustmann C, Tahk S, Shuai K, Grosschedl R, van Deursen JM (2008) Resolution of sister centromeres requires RanBP2-mediated SUMOylation of topoisomerase IIalpha. Cell 133:103–115PubMedCrossRefGoogle Scholar
  41. De Antoni A, Maffini S, Knapp S, Musacchio A, Santaguida S (2012) A small-molecule inhibitor of Haspin alters the kinetochore functions of Aurora B. J Cell Biol 199:269–284PubMedCrossRefGoogle Scholar
  42. De Wulf P, McAinsh AD, Sorger PK (2003) Hierarchical assembly of the budding yeast kinetochore from multiple subcomplexes. Genes Dev 17:2902–2921PubMedCrossRefGoogle Scholar
  43. DeLuca JG, Howell BJ, Canman JC, Hickey JM, Fang G, Salmon ED (2003) Nuf2 and Hec1 are required for retention of the checkpoint proteins Mad1 and Mad2 to kinetochores. Curr Biol 13:2103–2109PubMedCrossRefGoogle Scholar
  44. DeLuca JG, Gall WE, Ciferri C, Cimini D, Musacchio A, Salmon ED (2006) Kinetochore microtubule dynamics and attachment stability are regulated by Hec1. Cell 127:969–982PubMedCrossRefGoogle Scholar
  45. DeLuca KF, Lens SM, DeLuca JG (2011) Temporal changes in Hec1 phosphorylation control kinetochore–microtubule attachment stability during mitosis. J Cell Sci 124:622–634PubMedCrossRefGoogle Scholar
  46. Ditchfield C, Johnson VL, Tighe A, Ellston R, Haworth C, Johnson T, Mortlock A, Keen N, Taylor SS (2003) Aurora B couples chromosome alignment with anaphase by targeting BubR1, Mad2, and Cenp-E to kinetochores. J Cell Biol 161:267–280PubMedCrossRefGoogle Scholar
  47. Dohadwala M, Da Cruz e Silva EF, Hall FL, Williams RT, Carbonaro-Hall DA, Nairn AC, Greengard P, Berndt N (1994) Phosphorylation and inactivation of protein phosphatase 1 by cyclin-dependent kinases. Proc Natl Acad Sci U S A 91:6408–6412PubMedCrossRefGoogle Scholar
  48. Doonan JH, Morris NR (1989) The bimG gene of Aspergillus nidulans, required for completion of anaphase, encodes a homolog of mammalian phophoprotein phosphatase 1. Cell 57:987–996PubMedCrossRefGoogle Scholar
  49. Dumont S, Salmon ED, Mitchison TJ (2012) Deformations within moving kinetochores reveal different sites of active and passive force generation. Science 337:355–358PubMedCrossRefGoogle Scholar
  50. Dunsch AK, Linnane E, Barr FA, Gruneberg U (2011) The astrin–kinastrin/SKAP complex localizes to microtubule plus ends and facilitates chromosome alignment. J Cell Biol 192:959–968PubMedCrossRefGoogle Scholar
  51. Elia AE, Cantley LC, Yaffe MB (2003) Proteomic screen finds pSer/pThr-binding domain localizing Plk1 to mitotic substrates. Science 299:1228–1231PubMedCrossRefGoogle Scholar
  52. Elowe S, Hummer S, Uldschmid A, Li X, Nigg EA (2007) Tension-sensitive Plk1 phosphorylation on BubR1 regulates the stability of kinetochore microtubule interactions. Genes Dev 21:2205–2219PubMedCrossRefGoogle Scholar
  53. Emanuele MJ, Lan W, Jwa M, Miller SA, Chan CSM, Stukenberg PT (2008) Aurora B kinase and protein phosphatase 1 have opposing roles in modulating kinetochore assembly. J Cell Biol 181:241–254PubMedCrossRefGoogle Scholar
  54. Espeut J, Gaussen A, Bieling P, Morin V, Prieto S, Fesquet D, Surrey T, Abrieu A (2008) Phosphorylation relieves autoinhibition of the kinetochore motor Cenp-E. Mol Cell 29:637–643PubMedCrossRefGoogle Scholar
  55. Espeut J, Cheerambathur DK, Krenning L, Oegema K, Desai A (2012) Microtubule binding by KNL-1 contributes to spindle checkpoint silencing at the kinetochore. J Cell Biol 196:469–482PubMedCrossRefGoogle Scholar
  56. Fernius J, Hardwick KG (2007) Bub1 kinase targets Sgo1 to ensure efficient chromosome biorientation in budding yeast mitosis. PLoS Genet 3:e213PubMedCrossRefGoogle Scholar
  57. Firestone AJ, Weinger JS, Maldonado M, Barlan K, Langston LD, O'Donnell M, Gelfand VI, Kapoor TM, Chen JK (2012) Small-molecule inhibitors of the AAA + ATPase motor cytoplasmic dynein. Nature 484:125–129PubMedCrossRefGoogle Scholar
  58. Fisk HA, Winey M (2001) The mouse Mps1p-like kinase regulates centrosome duplication. Cell 106:95–104PubMedCrossRefGoogle Scholar
  59. Foley EA, Kapoor TM (2012) Microtubule attachment and spindle assembly checkpoint signalling at the kinetochore. Nat Rev Mol Cell Biol 14:25–37CrossRefGoogle Scholar
  60. Foley EA, Maldonado M, Kapoor TM (2011) Formation of stable attachments between kinetochores and microtubules depends on the B56-PP2A phosphatase. Nat Cell Biol 13:1265–1271PubMedCrossRefGoogle Scholar
  61. Foster SA, Morgan DO (2012) The APC/C subunit Mnd2/Apc15 promotes Cdc20 autoubiquitination and spindle assembly checkpoint inactivation. Mol Cell 47:921–932PubMedCrossRefGoogle Scholar
  62. Francisco L, Wang W, Chan CS (1994) Type 1 protein phosphatase acts in opposition to IpL1 protein kinase in regulating yeast chromosome segregation. Mol Cell Biol 14:4731–4740PubMedGoogle Scholar
  63. Gascoigne KE, Taylor SS (2008) Cancer cells display profound intra- and interline variation following prolonged exposure to antimitotic drugs. Cancer Cell 14:111–122PubMedCrossRefGoogle Scholar
  64. Gascoigne KE, Takeuchi K, Suzuki A, Hori T, Fukagawa T, Cheeseman IM (2011) Induced ectopic kinetochore assembly bypasses the requirement for CENP-A nucleosomes. Cell 145:410–422PubMedCrossRefGoogle Scholar
  65. Gassmann R, Holland AJ, Varma D, Wan X, Civril F, Cleveland DW, Oegema K, Salmon ED, Desai A (2010) Removal of Spindly from microtubule-attached kinetochores controls spindle checkpoint silencing in human cells. Genes Dev 24:957–971PubMedCrossRefGoogle Scholar
  66. Gestaut DR, Graczyk B, Cooper J, Widlund PO, Zelter A, Wordeman L, Asbury CL, Davis TN (2008) Phosphoregulation and depolymerization-driven movement of the Dam1 complex do not require ring formation. Nat Cell Biol 10:407–414PubMedCrossRefGoogle Scholar
  67. Good MC, Zalatan JG, Lim WA (2011) Scaffold proteins: hubs for controlling the flow of cellular information. Science 332:680–686PubMedCrossRefGoogle Scholar
  68. Gorbsky GJ, Ricketts WA (1993) Differential expression of a phosphoepitope at the kinetochores of moving chromosomes. J Cell Biol 122:1311–1321PubMedCrossRefGoogle Scholar
  69. Goto H, Kiyono T, Tomono Y, Kawajiri A, Urano T, Furukawa K, Nigg EA, Inagaki M (2006) Complex formation of Plk1 and INCENP required for metaphase–anaphase transition. Nat Cell Biol 8:180–187PubMedCrossRefGoogle Scholar
  70. Guimaraes GJ, Dong Y, McEwen BF, DeLuca JG (2008) Kinetochore–microtubule attachment relies on the disordered N-terminal tail domain of Hec1. Curr Biol 18:1778–1784PubMedCrossRefGoogle Scholar
  71. Guo Y, Kim C, Ahmad S, Zhang J, Mao Y (2012) CENP-E-dependent BubR1 autophosphorylation enhances chromosome alignment and the mitotic checkpoint. J Cell Biol 198:205–217PubMedCrossRefGoogle Scholar
  72. Guse A, Carroll CW, Moree B, Fuller CJ, Straight AF (2011) In vitro centromere and kinetochore assembly on defined chromatin templates. Nature 477:354–358PubMedCrossRefGoogle Scholar
  73. Hached K, Xie SZ, Buffin E, Cladiere D, Rachez C, Sacras M, Sorger PK, Wassmann K (2011) Mps1 at kinetochores is essential for female mouse meiosis I. Development 138:2261–2271PubMedCrossRefGoogle Scholar
  74. Hauf S, Cole RW, LaTerra S, Zimmer C, Schnapp G, Walter R, Heckel A, van Meel J, Rieder CL, Peters JM (2003) The small molecule Hesperadin reveals a role for Aurora B in correcting kinetochore–microtubule attachment and in maintaining the spindle assembly checkpoint. J Cell Biol 161:281–294PubMedCrossRefGoogle Scholar
  75. Hendrickx A, Beullens M, Ceulemans H, Den Abt T, Van Eynde A, Nicolaescu E, Lesage B, Bollen M (2009) Docking motif-guided mapping of the interactome of protein phosphatase-1. Chem Biol 16:365–371PubMedCrossRefGoogle Scholar
  76. Hewitt L, Tighe A, Santaguida S, White AM, Jones CD, Musacchio A, Green S, Taylor SS (2010) Sustained Mps1 activity is required in mitosis to recruit O-Mad2 to the Mad1–C-Mad2 core complex. J Cell Biol 190:25–34PubMedCrossRefGoogle Scholar
  77. Hood EA, Kettenbach AN, Gerber SA, Compton DA (2012) Plk1 regulates the kinesin-13 protein Kif2b to promote faithful chromosome segregation. Mol Biol Cell 23:2264–2274PubMedCrossRefGoogle Scholar
  78. Hori T, Okada M, Maenaka K, Fukagawa T (2008) CENP-O class proteins form a stable complex and are required for proper kinetochore function. Mol Biol Cell 19:843–854PubMedCrossRefGoogle Scholar
  79. 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 155:1159–1172PubMedCrossRefGoogle Scholar
  80. Howell BJ, Moree B, Farrar EM, Stewart S, Fang G, Salmon ED (2004) Spindle checkpoint protein dynamics at kinetochores in living cells. Curr Biol 14:953–964PubMedCrossRefGoogle Scholar
  81. Hsu JY, Sun ZW, Li X, Reuben M, Tatchell K, Bishop DK, Grushcow JM, Brame CJ, Caldwell JA, Hunt DF, Lin R, Smith MM, Allis CD (2000) Mitotic phosphorylation of histone H3 is governed by Ipl1/aurora kinase and Glc7/PP1 phosphatase in budding yeast and nematodes. Cell 102:279–291PubMedCrossRefGoogle Scholar
  82. Hua S, Wang Z, Jiang K, Huang Y, Ward T, Zhao L, Dou Z, Yao X (2011) CENP-U cooperates with Hec1 to orchestrate kinetochore–microtubule attachment. J Biol Chem 286:1627–1638PubMedCrossRefGoogle Scholar
  83. Huang H, Hittle J, Zappacosta F, Annan RS, Hershko A, Yen TJ (2008) Phosphorylation sites in BubR1 that regulate kinetochore attachment, tension, and mitotic exit. J Cell Biol 183:667–680PubMedCrossRefGoogle Scholar
  84. Hummer S, Mayer TU (2009) Cdk1 negatively regulates midzone localization of the mitotic kinesin Mklp2 and the chromosomal passenger complex. Curr Biol 19:607–612PubMedCrossRefGoogle Scholar
  85. Indjeian VB, Murray AW (2007) Budding yeast mitotic chromosomes have an intrinsic bias to biorient on the spindle. Curr Biol 17:1837–1846PubMedCrossRefGoogle Scholar
  86. Ito D, Saito Y, Matsumoto T (2011) Centromere-tethered Mps1 pombe homolog (Mph1) kinase is a sufficient marker for recruitment of the spindle checkpoint protein Bub1, but not Mad1. Proc Natl Acad Sci U S A 109:209–214PubMedCrossRefGoogle Scholar
  87. Jelluma N, Brenkman AB, van den Broek NJ, Cruijsen CW, van Osch MH, Lens SM, Medema RH, Kops GJ (2008) Mps1 phosphorylates Borealin to control Aurora B activity and chromosome alignment. Cell 132:233–246PubMedCrossRefGoogle Scholar
  88. Jeyaprakash AA, Santamaria A, Jayachandran U, Chan YW, Benda C, Nigg EA, Conti E (2012) Structural and functional organization of the Ska complex, a key component of the kinetochore–microtubule interface. Mol Cell 46:274–286PubMedCrossRefGoogle Scholar
  89. Jia L, Li B, Warrington RT, Hao X, Wang S, Yu H (2011) Defining pathways of spindle checkpoint silencing: functional redundancy between Cdc20 ubiquitination and p31(comet). Mol Biol Cell 22:4227–4235PubMedCrossRefGoogle Scholar
  90. Johnson VL, Scott MI, Holt SV, Hussein D, Taylor SS (2004) Bub1 is required for kinetochore localization of BubR1, Cenp-E, Cenp-F and Mad2, and chromosome congression. J Cell Sci 117:1577–1589PubMedCrossRefGoogle Scholar
  91. Kallio MJ, McCleland ML, Stukenberg PT, Gorbsky GJ (2002) Inhibition of aurora B kinase blocks chromosome segregation, overrides the spindle checkpoint, and perturbs microtubule dynamics in mitosis. Curr Biol 12:900–905PubMedCrossRefGoogle Scholar
  92. Kang YH, Park JE, Yu LR, Soung NK, Yun SM, Bang JK, Seong YS, Yu H, Garfield S, Veenstra TD, Lee KS (2006) Self-regulated Plk1 recruitment to kinetochores by the Plk1–PBIP1 interaction is critical for proper chromosome segregation. Mol Cell 24:409–422PubMedCrossRefGoogle Scholar
  93. Kapoor TM, Lampson MA, Hergert P, Cameron L, Cimini D, Salmon ED, McEwen BF, Khodjakov A (2006) Chromosomes can congress to the metaphase plate before biorientation. Science 311:388–391PubMedCrossRefGoogle Scholar
  94. Kasuboski JM, Bader JR, Vaughan PS, Tauhata SB, Winding M, Morrissey MA, Joyce MV, Boggess W, Vos L, Chan GK, Hinchcliffe EH, Vaughan KT (2011) Zwint-1 is a novel Aurora B substrate required for the assembly of a dynein-binding platform on kinetochores. Mol Biol Cell 22:3318–3330PubMedCrossRefGoogle Scholar
  95. Kawashima SA, Yamagishi Y, Honda T, Ishiguro K, Watanabe Y (2010) Phosphorylation of H2A by Bub1 prevents chromosomal instability through localizing shugoshin. Science 327:172–177PubMedCrossRefGoogle Scholar
  96. Kelly AE, Funabiki H (2009) Correcting aberrant kinetochore microtubule attachments: an Aurora B-centric view. Curr Opin Cell Biol 21:51–58PubMedCrossRefGoogle Scholar
  97. Kelly AE, Sampath SC, Maniar TA, Woo EM, Chait BT, Funabiki H (2007) Chromosomal enrichment and activation of the aurora B pathway are coupled to spatially regulate spindle assembly. Dev Cell 12:31–43PubMedCrossRefGoogle Scholar
  98. Kelly AE, Ghenoiu C, Xue JZ, Zierhut C, Kimura H, Funabiki H (2010) Survivin reads phosphorylated histone H3 threonine 3 to activate the mitotic kinase Aurora B. Science 330:235–239PubMedCrossRefGoogle Scholar
  99. Kemmler S, Stach M, Knapp M, Ortiz J, Pfannstiel J, Ruppert T, Lechner J (2009) Mimicking Ndc80 phosphorylation triggers spindle assembly checkpoint signalling. EMBO J 28:1099–1110PubMedCrossRefGoogle Scholar
  100. Kim Y, Holland AJ, Lan W, Cleveland DW (2010) Aurora kinases and protein phosphatase 1 mediate chromosome congression through regulation of CENP-E. Cell 142:444–455PubMedCrossRefGoogle Scholar
  101. King EM, Rachidi N, Morrice N, Hardwick KG, Stark MJ (2007a) Ipl1p-dependent phosphorylation of Mad3p is required for the spindle checkpoint response to lack of tension at kinetochores. Genes Dev 21:1163–1168PubMedCrossRefGoogle Scholar
  102. King EM, van der Sar SJ, Hardwick KG (2007b) Mad3 KEN boxes mediate both Cdc20 and Mad3 turnover, and are critical for the spindle checkpoint. PLoS One 2:e342PubMedCrossRefGoogle Scholar
  103. Kitajima TS, Sakuno T, Ishiguro K, Iemura S, Natsume T, Kawashima SA, Watanabe Y (2006) Shugoshin collaborates with protein phosphatase 2A to protect cohesin. Nature 441:46–52PubMedCrossRefGoogle Scholar
  104. Kitajima TS, Ohsugi M, Ellenberg J (2011) Complete kinetochore tracking reveals error-prone homologous chromosome biorientation in mammalian oocytes. Cell 146:568–581PubMedCrossRefGoogle Scholar
  105. Kiyomitsu T, Obuse C, Yanagida M (2007) Human Blinkin/AF15q14 is required for chromosome alignment and the mitotic checkpoint through direct interaction with Bub1 and BubR1. Dev Cell 13:663–676PubMedCrossRefGoogle Scholar
  106. Kiyomitsu T, Murakami H, Yanagida M (2011) Protein interaction domain mapping of human kinetochore protein Blinkin reveals a consensus motif for binding of spindle assembly checkpoint proteins Bub1 and BubR1. Mol Cell Biol 31:998–1011PubMedCrossRefGoogle Scholar
  107. Klebig C, Korinth D, Meraldi P (2009) Bub1 regulates chromosome segregation in a kinetochore-independent manner. J Cell Biol 185:841–858PubMedCrossRefGoogle Scholar
  108. Kline SL, Cheeseman IM, Hori T, Fukagawa T, Desai A (2006) The human Mis12 complex is required for kinetochore assembly and proper chromosome segregation. J Cell Biol 173:9–17PubMedCrossRefGoogle Scholar
  109. Knowlton AL, Lan W, Stukenberg PT (2006) Aurora B is enriched at merotelic attachment sites, where it regulates MCAK. Curr Biol 16:1705–1710PubMedCrossRefGoogle Scholar
  110. Knowlton AL, Vorozhko VV, Lan W, Gorbsky GJ, Stukenberg PT (2009) ICIS and Aurora B coregulate the microtubule depolymerase Kif2a. Curr Biol 19:758–763PubMedCrossRefGoogle Scholar
  111. Koivomagi M, Valk E, Venta R, Iofik A, Lepiku M, Balog ER, Rubin SM, Morgan DO, Loog M (2011) Cascades of multisite phosphorylation control Sic1 destruction at the onset of S phase. Nature 480:128–131PubMedCrossRefGoogle Scholar
  112. Kops GJ, Shah JV (2012) Connecting up and clearing out: how kinetochore attachment silences the spindle assembly checkpoint. Chromosoma 121:509–525PubMedCrossRefGoogle Scholar
  113. Kulukian A, Han JS, Cleveland DW (2009) Unattached kinetochores catalyze production of an anaphase inhibitor that requires a Mad2 template to prime Cdc20 for BubR1 binding. Dev Cell 16:105–117PubMedCrossRefGoogle Scholar
  114. Labit H, Fujimitsu K, Bayin NS, Takaki T, Gannon J, Yamano H (2012) Dephosphorylation of Cdc20 is required for its C-box-dependent activation of the APC/C. EMBO J 31:3351–3362Google Scholar
  115. Lampert F, Hornung P, Westermann S (2010) The Dam1 complex confers microtubule plus end-tracking activity to the Ndc80 kinetochore complex. J Cell Biol 189:641–649PubMedCrossRefGoogle Scholar
  116. Lampson MA, Cheeseman IM (2011) Sensing centromere tension: Aurora B and the regulation of kinetochore function. Trends Cell Biol 21(3):133–140PubMedCrossRefGoogle Scholar
  117. Lampson MA, Renduchitala K, Khodjakov A, Kapoor TM (2004) Correcting improper chromosome-spindle attachments during cell division. Nat Cell Biol 6:232–237PubMedCrossRefGoogle Scholar
  118. 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 microtubule depolymerization activity. Curr Biol 14:273–286PubMedGoogle Scholar
  119. Lara-Gonzalez P, Scott MI, Diez M, Sen O, Taylor SS (2011) BubR1 blocks substrate recruitment to the APC/C in a KEN-box-dependent manner. J Cell Sci 124:4332–4345PubMedCrossRefGoogle Scholar
  120. Lawrimore J, Bloom KS, Salmon ED (2011) Point centromeres contain more than a single centromere-specific Cse4 (CENP-A) nucleosome. J Cell Biol 195:573–582PubMedCrossRefGoogle Scholar
  121. Lee S, Thebault P, Freschi L, Beaufils S, Blundell TL, Landry CR, Bolanos-Garcia VM, Elowe S (2012) Characterization of spindle checkpoint kinase Mps1 reveals domain with functional and structural similarities to tetratricopeptide repeat motifs of Bub1 and BubR1 checkpoint kinases. J Biol Chem 287:5988–6001PubMedCrossRefGoogle Scholar
  122. Lenart P, Petronczki M, Steegmaier M, Di Fiore B, Lipp JJ, Hoffmann M, Rettig WJ, Kraut N, Peters JM (2007) The small-molecule inhibitor BI 2536 reveals novel insights into mitotic roles of polo-like kinase 1. Curr Biol 17:304–315PubMedCrossRefGoogle Scholar
  123. Lens SM, Rodriguez JA, Vader G, Span SW, Giaccone G, Medema RH (2006) Uncoupling the central spindle-associated function of the chromosomal passenger complex from its role at centromeres. Mol Biol Cell 17:1897–1909PubMedCrossRefGoogle Scholar
  124. Li Y, Benezra R (1996) Identification of a human mitotic checkpoint gene: hsMAD2. Science 274:246–248PubMedCrossRefGoogle Scholar
  125. Li H, Liu XS, Yang X, Wang Y, Wang Y, Turner JR, Liu X (2010) Phosphorylation of CLIP-170 by Plk1 and CK2 promotes timely formation of kinetochore–microtubule attachments. EMBO J 29:2953–2965PubMedCrossRefGoogle Scholar
  126. Lin YT, Chen Y, Wu G, Lee WH (2006) Hec1 sequentially recruits Zwint-1 and ZW10 to kinetochores for faithful chromosome segregation and spindle checkpoint control. Oncogene 25:6901–6914PubMedCrossRefGoogle Scholar
  127. 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 14:1638–1651PubMedCrossRefGoogle Scholar
  128. Liu D, Vader G, Vromans MJM, Lampson MA, Lens SMA (2009) Sensing chromosome bi-orientation by spatial separation of aurora B kinase from kinetochore substrates. Science 323:1350–1353PubMedCrossRefGoogle Scholar
  129. Liu D, Vleugel M, Backer CB, Hori T, Fukagawa T, Cheeseman IM, Lampson MA (2010) Regulated targeting of protein phosphatase 1 to the outer kinetochore by KNL1 opposes Aurora B kinase. J Cell Biol 188:809–820PubMedCrossRefGoogle Scholar
  130. Liu D, Davydenko O, Lampson MA (2012) Polo-like kinase-1 regulates kinetochore–microtubule dynamics and spindle checkpoint silencing. J Cell Biol 198:491–499PubMedCrossRefGoogle Scholar
  131. Logarinho E, Resende T, Torres C, Bousbaa H (2008) The human spindle assembly checkpoint protein bub3 is required for the establishment of efficient kinetochore–microtubule attachments. Mol Biol Cell 19:1798–1813PubMedCrossRefGoogle Scholar
  132. London N, Ceto S, Ranish JA, Biggins S (2012) Phosphoregulation of Spc105 by Mps1 and PP1 regulates Bub1 localization to kinetochores. Curr Biol 22:900–906PubMedCrossRefGoogle Scholar
  133. Luo X, Yu H (2008) Protein metamorphosis: the two-state behavior of Mad2. Structure 16:1616–1625PubMedCrossRefGoogle Scholar
  134. Maciejowski J, George KA, Terret ME, Zhang C, Shokat KM, Jallepalli PV (2010) Mps1 directs the assembly of Cdc20 inhibitory complexes during interphase and mitosis to control M phase timing and spindle checkpoint signaling. J Cell Biol 190:89–100PubMedCrossRefGoogle Scholar
  135. Magidson V, O'Connell CB, Loncarek J, Paul R, Mogilner A, Khodjakov A (2011) The spatial arrangement of chromosomes during prometaphase facilitates spindle assembly. Cell 146:555–567PubMedCrossRefGoogle Scholar
  136. Maldonado M, Kapoor TM (2011) Constitutive Mad1 targeting to kinetochores uncouples checkpoint signalling from chromosome biorientation. Nat Cell Biol 13:475–482PubMedCrossRefGoogle Scholar
  137. Malureanu LA, Jeganathan KB, Hamada M, Wasilewski L, Davenport J, van Deursen JM (2009) BubR1 N terminus acts as a soluble inhibitor of cyclin B degradation by APC/C(Cdc20) in interphase. Dev Cell 16:118–131PubMedCrossRefGoogle Scholar
  138. Manning AL, Bakhoum SF, Maffini S, Correia-Melo C, Maiato H, Compton DA (2010) CLASP1, astrin and Kif2b form a molecular switch that regulates kinetochore–microtubule dynamics to promote mitotic progression and fidelity. EMBO J 29:3531–3543PubMedCrossRefGoogle Scholar
  139. Mansfeld J, Collin P, Collins MO, Choudhary JS, Pines J (2011) APC15 drives the turnover of MCC-CDC20 to make the spindle assembly checkpoint responsive to kinetochore attachment. Nat Cell Biol 13:1234–1243PubMedCrossRefGoogle Scholar
  140. Mao Y, Abrieu A, Cleveland DW (2003) Activating and silencing the mitotic checkpoint through CENP-E-dependent activation/inactivation of BubR1. Cell 114:87–98PubMedCrossRefGoogle Scholar
  141. Mao Y, Desai A, Cleveland DW (2005) Microtubule capture by CENP-E silences BubR1-dependent mitotic checkpoint signaling. J Cell Biol 170:873–880PubMedCrossRefGoogle Scholar
  142. Maresca TJ, Salmon ED (2009) Intrakinetochore stretch is associated with changes in kinetochore phosphorylation and spindle assembly checkpoint activity. J Cell Biol 184:373–381PubMedCrossRefGoogle Scholar
  143. Maresca TJ, Salmon ED (2010) Welcome to a new kind of tension: translating kinetochore mechanics into a wait-anaphase signal. J Cell Sci 123:825–835PubMedCrossRefGoogle Scholar
  144. Martinez-Exposito MJ, Kaplan KB, Copeland J, Sorger PK (1999) Retention of the BUB3 checkpoint protein on lagging chromosomes. Proc Natl Acad Sci U S A 96:8493–8498PubMedCrossRefGoogle Scholar
  145. Martin-Lluesma S, Stucke VM, Nigg EA (2002) Role of Hec1 in spindle checkpoint signaling and kinetochore recruitment of Mad1/Mad2. Science 297:2267–2270PubMedCrossRefGoogle Scholar
  146. Matson DR, Demirel PB, Stukenberg PT, Burke DJ (2012) A conserved role for COMA/CENP-H/I/N kinetochore proteins in the spindle checkpoint. Genes Dev 26:542–547PubMedCrossRefGoogle Scholar
  147. Matsumura S, Toyoshima F, Nishida E (2007) Polo-like kinase 1 facilitates chromosome alignment during prometaphase through BubR1. J Biol Chem 282:15217–15227PubMedCrossRefGoogle Scholar
  148. Maure JF, Kitamura E, Tanaka TU (2007) Mps1 kinase promotes sister-kinetochore bi-orientation by a tension-dependent mechanism. Curr Biol 17:2175–2182PubMedCrossRefGoogle Scholar
  149. Mayer C, Filopei J, Batac J, Alford L, Paluh JL (2006) An extended anaphase signaling pathway for Mad2p includes microtubule organizing center proteins and multiple motor-dependent transitions. Cell Cycle 5:1456–1463PubMedCrossRefGoogle Scholar
  150. Meadows JC, Shepperd LA, Vanoosthuyse V, Lancaster TC, Sochaj AM, Buttrick GJ, Hardwick KG, Millar JB (2011) Spindle checkpoint silencing requires association of PP1 to both Spc7 and kinesin-8 motors. Dev Cell 20:739–750PubMedCrossRefGoogle Scholar
  151. Meraldi P, Sorger PK (2005) A dual role for Bub1 in the spindle checkpoint and chromosome congression. EMBO J 24:1621–1633PubMedCrossRefGoogle Scholar
  152. Meraldi P, Draviam VM, Sorger PK (2004) Timing and checkpoints in the regulation of mitotic progression. Dev Cell 7:45–60PubMedCrossRefGoogle Scholar
  153. Miller SA, Johnson ML, Stukenberg PT (2008) Kinetochore attachments require an interaction between unstructured tails on microtubules and Ndc80(Hec1). Curr Biol 18:1785–1791PubMedCrossRefGoogle Scholar
  154. Minoshima Y, Hori T, Okada M, Kimura H, Haraguchi T, Hiraoka Y, Bao YC, Kawashima T, Kitamura T, Fukagawa T (2005) The constitutive centromere component CENP-50 is required for recovery from spindle damage. Mol Cell Biol 25:10315–10328PubMedCrossRefGoogle Scholar
  155. Minshull J, Sun H, Tonks NK, Murray AW (1994) MAP-kinase dependent mitotic feedback arrest in Xenopus egg extracts. Cell 79:475–486PubMedCrossRefGoogle Scholar
  156. Morrow CJ, Tighe A, Johnson VL, Scott MI, Ditchfield C, Taylor SS (2005) Bub1 and aurora B cooperate to maintain BubR1-mediated inhibition of APC/CCdc20. J Cell Sci 118:3639–3652PubMedCrossRefGoogle Scholar
  157. Musacchio A, Salmon ED (2007) The spindle-assembly checkpoint in space and time. Nat Rev Mol Cell Biol 8:379–393PubMedCrossRefGoogle Scholar
  158. Nagaoka SI, Hassold TJ, Hunt PA (2012) Human aneuploidy: mechanisms and new insights into an age-old problem. Nat Rev Genet 13:493–504PubMedCrossRefGoogle Scholar
  159. Nicklas RB, Ward SC, Gorbsky GJ (1995) Kinetochore chemistry is sensitive to tension and may link mitotic forces to a cell cycle checkpoint. J Cell Biol 130:929–939PubMedCrossRefGoogle Scholar
  160. Nishino M, Kurasawa Y, Evans R, Lin SH, Brinkley BR, Yu-Lee LY (2006) NudC is required for Plk1 targeting to the kinetochore and chromosome congression. Curr Biol 16:1414–1421PubMedCrossRefGoogle Scholar
  161. Obuse C, Iwasaki O, Kiyomitsu T, Goshima G, Toyoda Y, Yanagida M (2004) A conserved Mis12 centromere complex is linked to heterochromatic HP1 and outer kinetochore protein Zwint-1. Nat Cell Biol 6:1135–1141PubMedCrossRefGoogle Scholar
  162. Ohi R, Sapra T, Howard J, Mitchison TJ (2004) Differentiation of cytoplasmic and meiotic spindle assembly MCAK functions by Aurora B-dependent phosphorylation. Mol Biol Cell 15:2895–2906PubMedCrossRefGoogle Scholar
  163. Ohkura H, Yanagida M (1991) S. pombe gene sds22+ essential for a midmitotic transition encodes a leucine-rich repeat protein that positively modulates protein phosphatase-1. Cell 64:149–157PubMedCrossRefGoogle Scholar
  164. Ohkura H, Noriyuki K, Miyatani S, Toda T, Yanagida M (1989) The fission yeast dis2 + gene required for chromosome disjoining encodes one of two putative type 1 protein phosphatases. Cell 57:997–1007PubMedCrossRefGoogle Scholar
  165. Park JE, Erikson RL, Lee KS (2011) Feed-forward mechanism of converting biochemical cooperativity to mitotic processes at the kinetochore plate. Proc Natl Acad Sci U S A 108:8200–8205PubMedCrossRefGoogle Scholar
  166. Parry DH, Hickson GR, O'Farrell PH (2003) Cyclin B destruction triggers changes in kinetochore behavior essential for successful anaphase. Curr Biol 13:647–653PubMedCrossRefGoogle Scholar
  167. Perera D, Taylor SS (2010) Sgo1 establishes the centromeric cohesion protection mechanism in G2 before subsequent Bub1-dependent recruitment in mitosis. J Cell Sci 123:653–659PubMedCrossRefGoogle Scholar
  168. Perpelescu M, Fukagawa T (2011) The ABCs of CENPs. Chromosoma 120:425–446PubMedCrossRefGoogle Scholar
  169. Peters JM (2006) The anaphase promoting complex/cyclosome: a machine designed to destroy. Nat Rev Mol Cell Biol 7:644–656PubMedCrossRefGoogle Scholar
  170. Petersen J, Hagan IM (2003) S. pombe aurora kinase/survivin is required for chromosome condensation and the spindle checkpoint attachment response. Curr Biol 13:590–597PubMedCrossRefGoogle Scholar
  171. Petrovic A, Pasqualato S, Dube P, Krenn V, Santaguida S, Cittaro D, Monzani S, Massimiliano L, Keller J, Tarricone A, Maiolica A, Stark H, Musacchio A (2010) The MIS12 complex is a protein interaction hub for outer kinetochore assembly. J Cell Biol 190:835–852PubMedCrossRefGoogle Scholar
  172. Pinsky BA, Kotwaliwale CV, Tatsutani SY, Breed CA, Biggins S (2006a) Glc7/protein phosphatase 1 regulatory subunits can oppose the Ipl1/aurora protein kinase by redistributing Glc7. Mol Cell Biol 26:2648–2660PubMedCrossRefGoogle Scholar
  173. Pinsky BA, Kung C, Shokat KM, Biggins S (2006b) The Ipl1-Aurora protein kinase activates the spindle checkpoint by creating unattached kinetochores. Nat Cell Biol 8:78–83PubMedCrossRefGoogle Scholar
  174. Pinsky BA, Nelson CR, Biggins S (2009) Protein phosphatase 1 regulates exit from the spindle checkpoint in budding yeast. Curr Biol 19:1182–1187PubMedCrossRefGoogle Scholar
  175. Pomerening JR, Sontag ED, Ferrell JE Jr (2003) Building a cell cycle oscillator: hysteresis and bistability in the activation of Cdc2. Nat Cell Biol 5:346–351PubMedCrossRefGoogle Scholar
  176. Posch M, Khoudoli GA, Swift S, King EM, DeLuca JG, Swedlow JR (2010) Sds22 regulates aurora B activity and microtubule–kinetochore interactions at mitosis. J Cell Biol 191:61–74PubMedCrossRefGoogle Scholar
  177. Przewloka MR, Glover DM (2009) The kinetochore and the centromere: a working long distance relationship. Annu Rev Genet 43:439–465PubMedCrossRefGoogle Scholar
  178. Qi W, Tang Z, Yu H (2006) Phosphorylation- and polo-box-dependent binding of Plk1 to Bub1 is required for the kinetochore localization of Plk1. Mol Biol Cell 17:3705–3716PubMedCrossRefGoogle Scholar
  179. Reddy SK, Rape M, Margansky WA, Kirschner MW (2007) Ubiquitination by the anaphase-promoting complex drives spindle checkpoint inactivation. Nature 446:921–925PubMedCrossRefGoogle Scholar
  180. Ricke RM, Jeganathan KB, Malureanu L, Harrison AM, van Deursen JM (2012) Bub1 kinase activity drives error correction and mitotic checkpoint control but not tumor suppression. J Cell Biol 199:931–949PubMedCrossRefGoogle Scholar
  181. Riedel CG, Katis VL, Katou Y, Mori S, Itoh T, Helmhart W, Galova M, Petronczki M, Gregan J, Cetin B, Mudrak I, Ogris E, Mechtler K, Pelletier L, Buchholz F, Shirahige K, Nasmyth K (2006) Protein phosphatase 2A protects centromeric sister chromatid cohesion during meiosis I. Nature 441:53–61PubMedCrossRefGoogle Scholar
  182. 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(1):81–95PubMedCrossRefGoogle Scholar
  183. Rieder CL, Schultz A, Cole R, Sluder G (1994) Anaphase onset in vertebrate somatic cells is controlled by a checkpoint that monitors sister kinetochore attachment to the spindle. J Cell Biol 127:1301–1310PubMedCrossRefGoogle Scholar
  184. 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 130:941–948PubMedCrossRefGoogle Scholar
  185. Rischitor PE, May KM, Hardwick KG (2007) Bub1 is a fission yeast kinetochore scaffold protein, and is sufficient to recruit other spindle checkpoint proteins to ectopic sites on chromosomes. PLoS One 2:e1342PubMedCrossRefGoogle Scholar
  186. Rosasco-Nitcher SE, Lan W, Khorasanizadeh S, Stukenberg PT (2008) Centromeric Aurora-B activation requires TD-60, microtubules, and substrate priming phosphorylation. Science 319:469–472PubMedCrossRefGoogle Scholar
  187. Rosenberg JS, Cross FR, Funabiki H (2011) KNL1/Spc105 recruits PP1 to silence the spindle assembly checkpoint. Curr Biol 21:942–947PubMedCrossRefGoogle Scholar
  188. Ryu H, Furuta M, Kirkpatrick D, Gygi SP, Azuma Y (2010) PIASy-dependent SUMOylation regulates DNA topoisomerase IIalpha activity. J Cell Biol 191:783–794PubMedCrossRefGoogle Scholar
  189. Sakuno T, Tada K, Watanabe Y (2009) Kinetochore geometry defined by cohesion within the centromere. Nature 458:852–858PubMedCrossRefGoogle Scholar
  190. Salimian KJ, Ballister ER, Smoak EM, Wood S, Panchenko T, Lampson MA, Black BE (2011) Feedback control in sensing chromosome biorientation by the Aurora B kinase. Curr Biol 21:1158–1165PubMedCrossRefGoogle Scholar
  191. Santaguida S, Vernieri C, Villa F, Ciliberto A, Musacchio A (2011) Evidence that Aurora B is implicated in spindle checkpoint signalling independently of error correction. EMBO J 30:1508–1519PubMedCrossRefGoogle Scholar
  192. Saurin AT, van der Waal MS, Medema RH, Lens SM, Kops GJ (2011) Aurora B potentiates Mps1 activation to ensure rapid checkpoint establishment at the onset of mitosis. Nat Commun 2:316PubMedCrossRefGoogle Scholar
  193. Schaar BT, Chan GK, Maddox P, Salmon ED, Yen TJ (1997) CENP-E function at kinetochores is essential for chromosome alignment. J Cell Biol 139:1373–1382PubMedCrossRefGoogle Scholar
  194. Schmidt JC, Kiyomitsu T, Hori T, Backer CB, Fukagawa T, Cheeseman IM (2010) Aurora B kinase controls the targeting of the Astrin–SKAP complex to bioriented kinetochores. J Cell Biol 191:269–280PubMedCrossRefGoogle Scholar
  195. Schmidt JC, Arthanari H, Boeszoermenyi A, Dashkevich NM, Wilson-Kubalek EM, Monnier N, Markus M, Oberer M, Milligan RA, Bathe M, Wagner G, Grishchuk EL, Cheeseman IM (2012) The kinetochore-bound Ska1 complex tracks depolymerizing microtubules and binds to curved protofilaments. Dev Cell 23(5):968–980PubMedCrossRefGoogle Scholar
  196. Sczaniecka M, Feoktistova A, May KM, Chen JS, Blyth J, Gould KL, Hardwick KG (2008) The spindle checkpoint functions of Mad3 and Mad2 depend on a Mad3 KEN box-mediated interaction with Cdc20-anaphase-promoting complex (APC/C). J Biol Chem 283:23039–23047PubMedCrossRefGoogle Scholar
  197. Shah JV, Botvinick E, Bonday Z, Furnari F, Berns M, Cleveland DW (2004) Dynamics of centromere and kinetochore proteins; implications for checkpoint signaling and silencing. Curr Biol 14:942–952PubMedGoogle Scholar
  198. Shapiro PS, Vaisberg E, Hunt AJ, Tolwinski NS, Whalen AM, McIntosh JR, Ahn NG (1998) Activation of the MKK/ERK pathway during somatic cell mitosis: direct interactions of active ERK with kinetochores and regulation of the mitotic 3F3/2 phosphoantigen. J Cell Biol 142:1533–1545PubMedCrossRefGoogle Scholar
  199. Sharp-Baker H, Chen RH (2001) Spindle checkpoint protein Bub1 is required for kinetochore localization of Mad1, Mad2, Bub3, and CENP-E, independently of its kinase activity. J Cell Biol 153:1239–1250PubMedCrossRefGoogle Scholar
  200. Shepperd LA, Meadows JC, Sochaj AM, Lancaster TC, Zou J, Buttrick GJ, Rappsilber J, Hardwick KG, Millar JB (2012) Phosphodependent recruitment of Bub1 and Bub3 to Spc7/KNL1 by Mph1 kinase maintains the spindle checkpoint. Curr Biol 22:891–899PubMedCrossRefGoogle Scholar
  201. Sliedrecht T, Zhang C, Shokat KM, Kops GJ (2010) Chemical genetic inhibition of Mps1 in stable human cell lines reveals novel aspects of Mps1 function in mitosis. PLoS One 5:e10251PubMedCrossRefGoogle Scholar
  202. Stegmeier F, Rape M, Draviam VM, Nalepa G, Sowa ME, Ang XL, McDonald ER 3rd, Li MZ, Hannon GJ, Sorger PK, Kirschner MW, Harper JW, Elledge SJ (2007) Anaphase initiation is regulated by antagonistic ubiquitination and deubiquitination activities. Nature 446:876–881PubMedCrossRefGoogle Scholar
  203. Stone EM, Yamano H, Kinoshita N, Yanagida M (1993) Mitotic regulation of protein phosphatases by the fission yeast sds22 protein. Curr Biol 3:13–26PubMedCrossRefGoogle Scholar
  204. Stucke VM, Sillje HH, Arnaud L, Nigg EA (2002) Human Mps1 kinase is required for the spindle assembly checkpoint but not for centrosome duplication. EMBO J 21:1723–1732PubMedCrossRefGoogle Scholar
  205. Stucke VM, Baumann C, Nigg EA (2004) Kinetochore localization and microtubule interaction of the human spindle checkpoint kinase Mps1. Chromosoma 113:1–15PubMedCrossRefGoogle Scholar
  206. Stumpff J, von Dassow G, Wagenbach M, Asbury C, Wordeman L (2008) The kinesin-8 motor Kif18A suppresses kinetochore movements to control mitotic chromosome alignment. Dev Cell 14:252–262PubMedCrossRefGoogle Scholar
  207. 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 154:925–936PubMedCrossRefGoogle Scholar
  208. Suijkerbuijk SJ, van Dam TJ, Karagoz GE, von Castelmur E, Hubner NC, Duarte AM, Vleugel M, Perrakis A, Rudiger SG, Snel B, Kops GJ (2012a) The vertebrate mitotic checkpoint protein BUBR1 is an unusual pseudokinase. Dev Cell 22:1321–1329PubMedCrossRefGoogle Scholar
  209. Suijkerbuijk SJ, Vleugel M, Teixeira A, Kops GJ (2012b) Integration of kinase and phosphatase activities by BUBR1 ensures formation of stable kinetochore–microtubule attachments. Dev Cell 23:745–755PubMedCrossRefGoogle Scholar
  210. Suzuki A, Hori T, Nishino T, Usukura J, Miyagi A, Morikawa K, Fukagawa T (2011) Spindle microtubules generate tension-dependent changes in the distribution of inner kinetochore proteins. J Cell Biol 193:125–140PubMedCrossRefGoogle Scholar
  211. Takeda DY, Wohlschlegel JA, Dutta A (2001) A bipartite substrate recognition motif for cyclin-dependent kinases. J Biol Chem 276:1993–1997PubMedCrossRefGoogle Scholar
  212. Takenaka K, Gotoh Y, Nishida E (1997) MAP kinase is required for the spindle assembly checkpoint but is dispensable for the normal M phase entry and exit in Xenopus egg cell cycle extracts. J Cell Biol 136:1091–1097PubMedCrossRefGoogle Scholar
  213. Takeuchi K, Fukagawa T (2012) Molecular architecture of vertebrate kinetochores. Exp Cell Res 318:1367–1374PubMedCrossRefGoogle Scholar
  214. Tanaka TU (2010) Kinetochore-microtubule interactions: steps towards bi-orientation. EMBO J 29:4070–4082PubMedCrossRefGoogle Scholar
  215. 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 108:317–329PubMedCrossRefGoogle Scholar
  216. Tanaka K, Mukae N, Dewar H, van Breugel M, James EK, Prescott AR, Antony C, Tanaka TU (2005) Molecular mechanisms of kinetochore capture by spindle microtubules. Nature 434:987–994PubMedCrossRefGoogle Scholar
  217. Tang Z, Bharadwaj R, Li B, Yu H (2001) Mad2-independent inhibition of APCCdc20 by the mitotic checkpoint protein BubR1. Dev Cell 1:227–237PubMedCrossRefGoogle Scholar
  218. Tang Z, Shu H, Oncel D, Chen S, Yu H (2004) Phosphorylation of Cdc20 by Bub1 provides a catalytic mechanism for APC/C inhibition by the spindle checkpoint. Mol Cell 16:387–397PubMedCrossRefGoogle Scholar
  219. Tang Z, Shu H, Qi W, Mahmood NA, Mumby MC, Yu H (2006) PP2A is required for centromeric localization of Sgo1 and proper chromosome segregation. Dev Cell 10:575–585PubMedCrossRefGoogle Scholar
  220. Tanno Y, Kitajima TS, Honda T, Ando Y, Ishiguro K, Watanabe Y (2010) Phosphorylation of mammalian Sgo2 by Aurora B recruits PP2A and MCAK to centromeres. Genes Dev 24:2169–2179PubMedCrossRefGoogle Scholar
  221. Taylor SS, McKeon F (1997) Kinetochore localization of murine Bub1 is required for normal mitotic timing and checkpoint response to spindle damage. Cell 89:727–735PubMedCrossRefGoogle Scholar
  222. 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 142:1–11PubMedCrossRefGoogle Scholar
  223. Teichner A, Eytan E, Sitry-Shevah D, Miniowitz-Shemtov S, Dumin E, Gromis J, Hershko A (2011) p31comet promotes disassembly of the mitotic checkpoint complex in an ATP-dependent process. Proc Natl Acad Sci U S A 108:3187–3192PubMedCrossRefGoogle Scholar
  224. Tien JF, Umbreit NT, Gestaut DR, Franck AD, Cooper J, Wordeman L, Gonen T, Asbury CL, Davis TN (2010) Cooperation of the Dam1 and Ndc80 kinetochore complexes enhances microtubule coupling and is regulated by aurora B. J Cell Biol 189:713–723PubMedCrossRefGoogle Scholar
  225. Tighe A, Staples O, Taylor S (2008) Mps1 kinase activity restrains anaphase during an unperturbed mitosis and targets Mad2 to kinetochores. J Cell Biol 181:893–901PubMedCrossRefGoogle Scholar
  226. Tooley JG, Miller SA, Stukenberg PT (2011) The Ndc80 complex uses a tripartite attachment point to couple microtubule depolymerization to chromosome movement. Mol Biol Cell 22:1217–1226PubMedCrossRefGoogle Scholar
  227. Trinkle-Mulcahy L, Andrews PD, Wickramasinghe S, Sleeman J, Prescott A, Lam YW, Lyon C, Swedlow JR, Lamond AI (2003) Time-lapse imaging reveals dynamic relocalization of PP1gamma throughout the mammalian cell cycle. Mol Biol Cell 14:107–117PubMedCrossRefGoogle Scholar
  228. Trinkle-Mulcahy L, Andersen J, Lam YW, Moorhead G, Mann M, Lamond AI (2006) Repo-Man recruits PP1 gamma to chromatin and is essential for cell viability. J Cell Biol 172:679–692PubMedCrossRefGoogle Scholar
  229. Tseng BS, Tan L, Kapoor TM, Funabiki H (2010) Dual detection of chromosomes and microtubules by the chromosomal passenger complex drives spindle assembly. Dev Cell 18:903–912PubMedCrossRefGoogle Scholar
  230. Tsukahara T, Tanno Y, Watanabe Y (2010) Phosphorylation of the CPC by Cdk1 promotes chromosome bi-orientation. Nature 467:719–723PubMedCrossRefGoogle Scholar
  231. Ubersax JA, Woodbury EL, Quang PN, Paraz M, Blethrow JD, Shah K, Shokat KM, Morgan DO (2003) Targets of the cyclin-dependent kinase Cdk1. Nature 425:859–864PubMedCrossRefGoogle Scholar
  232. Uchida KS, Takagaki K, Kumada K, Hirayama Y, Noda T, Hirota T (2009) Kinetochore stretching inactivates the spindle assembly checkpoint. J Cell Biol 184:383–390PubMedCrossRefGoogle Scholar
  233. Uzunova K, Dye BT, Schutz H, Ladurner R, Petzold G, Toyoda Y, Jarvis MA, Brown NG, Poser I, Novatchkova M, Mechtler K, Hyman AA, Stark H, Schulman BA, Peters JM (2012) APC15 mediates CDC20 autoubiquitylation by APC/C(MCC) and disassembly of the mitotic checkpoint complex. Nat Struct Mol Biol 19:1116–1123PubMedCrossRefGoogle Scholar
  234. van der Waal MS, Hengeveld RC, van der Horst A, Lens SM (2012) Cell division control by the chromosomal passenger complex. Exp Cell Res 318:1407–1420PubMedCrossRefGoogle Scholar
  235. Vanoosthuyse V, Hardwick KG (2009) A novel protein phosphatase 1-dependent spindle checkpoint silencing mechanism. Curr Biol 19:1176–1181PubMedCrossRefGoogle Scholar
  236. Varma D, Monzo P, Stehman SA, Vallee RB (2008) Direct role of dynein motor in stable kinetochore–microtubule attachment, orientation, and alignment. J Cell Biol 182:1045–1054PubMedCrossRefGoogle Scholar
  237. Vigneron S, Prieto S, Bernis C, Labbe JC, Castro A, Lorca T (2004) Kinetochore localization of spindle checkpoint proteins: who controls whom? Mol Biol Cell 15:4584–4596PubMedCrossRefGoogle Scholar
  238. Vorozhko VV, Emanuele MJ, Kallio MJ, Stukenberg PT, Gorbsky GJ (2008) Multiple mechanisms of chromosome movement in vertebrate cells mediated through the Ndc80 complex and dynein/dynactin. Chromosoma 117:169–179PubMedCrossRefGoogle Scholar
  239. Wan X, O'Quinn RP, Pierce HL, Joglekar AP, Gall WE, DeLuca JG, Carroll CW, Liu ST, Yen TJ, McEwen BF, Stukenberg PT, Desai A, Salmon ED (2009) Protein architecture of the human kinetochore microtubule attachment site. Cell 137:672–684PubMedCrossRefGoogle Scholar
  240. Wang XM, Zhai Y, Ferrell JE Jr (1997) A role for mitogen-activated protein kinase in the spindle assembly checkpoint in XTC cells. J Cell Biol 137:433–443PubMedCrossRefGoogle Scholar
  241. Wang HW, Ramey VH, Westermann S, Leschziner AE, Welburn JP, Nakajima Y, Drubin DG, Barnes G, Nogales E (2007) Architecture of the Dam1 kinetochore ring complex and implications for microtubule-driven assembly and force-coupling mechanisms. Nat Struct Mol Biol 14:721–726PubMedCrossRefGoogle Scholar
  242. Wang F, Dai J, Daum JR, Niedzialkowska E, Banerjee B, Stukenberg PT, Gorbsky GJ, Higgins JM (2010) Histone H3 Thr-3 phosphorylation by Haspin positions Aurora B at centromeres in mitosis. Science 330:231–235PubMedCrossRefGoogle Scholar
  243. Wang F, Ulyanova NP, van der Waal MS, Patnaik D, Lens SM, Higgins JM (2011) A positive feedback loop involving Haspin and Aurora B promotes CPC accumulation at centromeres in mitosis. Curr Biol 21:1061–1069PubMedCrossRefGoogle Scholar
  244. Wang F, Ulyanova NP, Daum JR, Patnaik D, Kateneva AV, Gorbsky GJ, Higgins JM (2012) Haspin inhibitors reveal centromeric functions of Aurora B in chromosome segregation. J Cell Biol 199:251–268PubMedCrossRefGoogle Scholar
  245. Warren CD, Brady DM, Johnston RC, Hanna JS, Hardwick KG, Spencer FA (2002) Distinct chromosome segregation roles for spindle checkpoint proteins. Mol Biol Cell 13:3029–3041PubMedCrossRefGoogle Scholar
  246. Waters JC, Chen RH, Murray AW, Salmon ED (1998) Localization of Mad2 to kinetochores depends on microtubule attachment, not tension. J Cell Biol 141:1181–1191PubMedCrossRefGoogle Scholar
  247. Weaver BA, Cleveland DW (2006) Does aneuploidy cause cancer? Curr Opin Cell Biol 18:658–667PubMedCrossRefGoogle Scholar
  248. Wei RR, Al-Bassam J, Harrison SC (2007) The Ndc80/HEC1 complex is a contact point for kinetochore–microtubule attachment. Nat Struct Mol Biol 14:54–59PubMedCrossRefGoogle Scholar
  249. Wei R, Ngo B, Wu G, Lee WH (2011) Phosphorylation of the Ndc80 complex protein, HEC1, by Nek2 kinase modulates chromosome alignment and signaling of the spindle assembly checkpoint. Mol Biol Cell 22:3584–3594PubMedCrossRefGoogle Scholar
  250. Welburn JPI, Vleugel M, Liu D, Iii JRY, Lampson MA, Fukagawa T, Cheeseman IM (2010) Aurora B phosphorylates spatially distinct targets to differentially regulate the kinetochore–microtubule interface. Mol Cell 38:383–392PubMedCrossRefGoogle Scholar
  251. Westhorpe FG, Tighe A, Lara-Gonzalez P, Taylor SS (2011) p31comet-mediated extraction of Mad2 from the MCC promotes efficient mitotic exit. J Cell Sci 124:3905–3916PubMedCrossRefGoogle Scholar
  252. Wong OK, Fang G (2007) Cdk1 phosphorylation of BubR1 controls spindle checkpoint arrest and Plk1-mediated formation of the 3F3/2 epitope. J Cell Biol 179:611–617PubMedCrossRefGoogle Scholar
  253. Wood KW, Sakowicz R, Goldstein LS, Cleveland DW (1997) CENP-E is a plus end-directed kinetochore motor required for metaphase chromosome alignment. Cell 91:357–366PubMedCrossRefGoogle Scholar
  254. Wurzenberger C, Held M, Lampson MA, Poser I, Hyman AA, Gerlich DW (2012) Sds22 and Repo-Man stabilize chromosome segregation by counteracting Aurora B on anaphase kinetochores. J Cell Biol 198:173–183PubMedCrossRefGoogle Scholar
  255. Yamagishi Y, Honda T, Tanno Y, Watanabe Y (2010) Two histone marks establish the inner centromere and chromosome bi-orientation. Science 330:239–243PubMedCrossRefGoogle Scholar
  256. Yamagishi Y, Yang CH, Tanno Y, Watanabe Y (2012) MPS1/Mph1 phosphorylates the kinetochore protein KNL1/Spc7 to recruit SAC components. Nat Cell Biol 14:746–752PubMedCrossRefGoogle Scholar
  257. Yamano H, Ishii K, Yanagida M (1994) Phosphorylation of dis2 protein phosphatase at the C-terminal cdc2 consensus and its potential role in cell cycle regulation. EMBO J 13:5310–5318PubMedGoogle Scholar
  258. Yang M, Li B, Liu CJ, Tomchick DR, Machius M, Rizo J, Yu H, Luo X (2008) Insights into mad2 regulation in the spindle checkpoint revealed by the crystal structure of the symmetric mad2 dimer. PLoS Biol 6:e50PubMedCrossRefGoogle Scholar
  259. Yasuda S, Oceguera-Yanez F, Kato T, Okamoto M, Yonemura S, Terada Y, Ishizaki T, Narumiya S (2004) Cdc42 and mDia3 regulate microtubule attachment to kinetochores. Nature 428:767–771PubMedCrossRefGoogle Scholar
  260. 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 130:687–700PubMedCrossRefGoogle Scholar
  261. Yue Z, Carvalho A, Xu Z, Yuan X, Cardinale S, Ribeiro S, Lai F, Ogawa H, Gudmundsdottir E, Gassmann R, Morrison CG, Ruchaud S, Earnshaw WC (2008) Deconstructing Survivin: comprehensive genetic analysis of Survivin function by conditional knockout in a vertebrate cell line. J Cell Biol 183:279–296PubMedCrossRefGoogle Scholar
  262. Zecevic M, Catling AD, Eblen ST, Renzi L, Hittle JC, Yen TJ, Gorbsky GJ, Weber MJ (1998) Active MAP kinase in mitosis: localization at kinetochores and association with the motor protein CENP-E. J Cell Biol 142:1547–1558PubMedCrossRefGoogle Scholar
  263. Zhang J, Ahmad S, Mao Y (2007) BubR1 and APC/EB1 cooperate to maintain metaphase chromosome alignment. J Cell Biol 178:773–784PubMedCrossRefGoogle Scholar
  264. Zhao Y, Chen RH (2006) Mps1 phosphorylation by MAP kinase is required for kinetochore localization of spindle-checkpoint proteins. Curr Biol 16:1764–1769PubMedCrossRefGoogle Scholar
  265. Zhou T, Aumais JP, Liu X, Yu-Lee LY, Erikson RL (2003) A role for Plk1 phosphorylation of NudC in cytokinesis. Dev Cell 5:127–138PubMedCrossRefGoogle Scholar
  266. Zich J, Sochaj AM, Syred HM, Milne L, Cook AG, Ohkura H, Rappsilber J, Hardwick KG (2012) Kinase activity of fission yeast Mph1 is required for Mad2 and Mad3 to stably bind the anaphase promoting complex. Curr Biol 22:296–301PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  1. 1.Laboratory of Chromosome and Cell BiologyThe Rockefeller UniversityNew YorkUSA

Personalised recommendations