, Volume 121, Issue 5, pp 509–525 | Cite as

Connecting up and clearing out: how kinetochore attachment silences the spindle assembly checkpoint



With the goal of creating two genetically identical daughter cells, cell division culminates in the equal segregation of sister chromatids. This phase of cell division is monitored by a cell cycle checkpoint known as the spindle assembly checkpoint (SAC). The SAC actively prevents chromosome segregation while one or more chromosomes, or more accurately kinetochores, remain unattached to the mitotic spindle. Such unattached kinetochores recruit SAC proteins to assemble a diffusible anaphase inhibitor. Kinetochores stop production of this inhibitor once microtubules (MTs) of the mitotic spindle are bound, but productive attachment of all kinetochores is required to satisfy the SAC, initiate anaphase, and exit from mitosis. Although mechanisms of kinetochore signaling and SAC inhibitor assembly and function have received the bulk of attention in the past two decades, recent work has focused on the principles of SAC silencing. Here, we review the mechanisms that silence SAC signaling at the kinetochore, and in particular, how attachment to spindle MTs and biorientation on the mitotic spindle may turn off inhibitor generation. Future challenges in this area are highlighted towards the goal of building a comprehensive molecular model of this process.


Spindle assembly checkpoint






Centromere protein


Knl1/Mis12/Ndc80 complex


Chromosome passenger complex


Tandem affinity purification


Cyclin-dependent kinase 1


Anaphase promoting complex/cyclosome


Mitotic checkpoint complex


Dynein intermediate chain


  1. Abrieu A, Magnaghi-Jaulin L, Kahana JA, Peter M, Castro A, Vigneron S, Lorca T, Cleveland DW, Labbé JC (2001) Mps1 is a kinetochore-associated kinase essential for the vertebrate mitotic checkpoint. Cell 106(1):83–93PubMedCrossRefGoogle Scholar
  2. Alexander J, Lim D, Joughin BA, Hegemann B, Hutchins JRA, Ehrenberger T, Ivins F, Sessa F, Hudecz O, Nigg EA, Fry AM, Musacchio A, Stukenberg PT, Mechtler K, Peters J-M, 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(179):ra42. doi:10.1126/scisignal.2001796 PubMedCrossRefGoogle Scholar
  3. Amaro AC, Samora CP, Holtackers R, Wang E, Kingston IJ, Alonso M, Lampson M, McAinsh AD, Meraldi P (2010) Molecular control of kinetochore-microtubule dynamics and chromosome oscillations. Nat Cell Biol 12(4):319–329. doi:10.1038/ncb2033 PubMedCrossRefGoogle Scholar
  4. Arasaki K, Tani K, Yoshimori T, Stephens DJ, Tagaya M (2007) Nordihydroguaiaretic acid affects multiple dynein-dynactin functions in interphase and mitotic cells. Mol Pharmacol 71(2):454–460. doi:10.1124/mol.106.029611 PubMedCrossRefGoogle Scholar
  5. Arnaud L, Pines J, Nigg EA (1998) GFP tagging reveals human Polo-like kinase 1 at the kinetochore/centromere region of mitotic chromosomes. Chromosoma 107(6–7):424–429PubMedCrossRefGoogle Scholar
  6. Barisic M, Sohm B, Mikolcevic P, Wandke C, Rauch V, Ringer T, Hess M, Bonn G, Geley S (2010) Spindly/CCDC99 is required for efficient chromosome congression and mitotic checkpoint regulation. Mol Biol Cell 21(12):1968. doi:10.1091/mbc.E09-04-0356 PubMedCrossRefGoogle Scholar
  7. Basto R, Scaerou F, Mische S, Wojcik E, Lefebvre C, Gomes R, Hays T, Karess R (2004) In vivo dynamics of the rough deal checkpoint protein during Drosophila mitosis. Curr Biol 14(1):56–61PubMedCrossRefGoogle Scholar
  8. 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(12):4847–4858. doi:10.1091/mbc.E06-06-0539 PubMedCrossRefGoogle Scholar
  9. 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(23):3118–3129. doi:10.1101/gad.934801 PubMedCrossRefGoogle Scholar
  10. Bolanos-Garcia VM, Lischetti T, Matak-Vinković D, Cota E, Simpson PJ, Chirgadze DY, Spring DR, Robinson CV, Nilsson J, Blundell TL (2011) Structure of a Blinkin-BUBR1 complex reveals an interaction crucial for kinetochore-mitotic checkpoint regulation via an unanticipated binding Site. Struct (London, England: 1993 19(11):1691–1700. doi:10.1016/j.str.2011.09.017 CrossRefGoogle Scholar
  11. Bomont P, Maddox P, Shah JV, Desai AB, Cleveland DW (2005) Unstable microtubule capture at kinetochores depleted of the centromere-associated protein CENP-F. EMBO J 24(22):3927–3939PubMedCrossRefGoogle Scholar
  12. Braunstein I, Miniowitz S, Moshe Y, Hershko A (2007) Inhibitory factors associated with anaphase-promoting complex/cylosome in mitotic checkpoint. Proc Natl Acad Sci U S A 104(12):4870–4875PubMedCrossRefGoogle Scholar
  13. Buffin E, Lefebvre C, Huang J, Gagou ME, Karess RE (2005) Recruitment of Mad2 to the kinetochore requires the Rod/Zw10 complex. Curr Biol 15(9):856–861. doi:10.1016/j.cub.2005.03.052 PubMedCrossRefGoogle Scholar
  14. 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(12):944–947. doi:10.1038/35046598 PubMedCrossRefGoogle Scholar
  15. Chan YW, Fava LL, Uldschmid A, Schmitz MHA, Gerlich DW, Nigg EA, Santamaria A (2009) Mitotic control of kinetochore-associated dynein and spindle orientation by human Spindly. J Cell Biol 185(5):859–874. doi:10.1083/jcb.200812167 PubMedCrossRefGoogle Scholar
  16. 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(5):563–571. doi:10.1083/jcb.201109001 PubMedCrossRefGoogle Scholar
  17. Chao WCH, Kulkarni K, Zhang Z, Kong EH, Barford D (2012) Structure of the mitotic checkpoint complex. Nature. doi:10.1038/nature10896
  18. 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(18):2255–2268PubMedCrossRefGoogle Scholar
  19. Chen RH, Waters JC, Salmon ED, Murray AW (1996) Association of spindle assembly checkpoint component XMAD2 with unattached kinetochores. Science 274(5285):242–246PubMedCrossRefGoogle Scholar
  20. Chen RH, Shevchenko A, Mann M, Murray AW (1998) Spindle checkpoint protein Xmad1 recruits Xmad2 to unattached kinetochores. J Cell Biol 143(2):283–295PubMedCrossRefGoogle Scholar
  21. Chen Q, Zhang X, Jiang Q, Clarke PR, Zhang C (2008) Cyclin B1 is localized to unattached kinetochores and contributes to efficient microtubule attachment and proper chromosome alignment during mitosis. Cell Research 18(2):268–280. doi:10.1038/cr.2008.11 PubMedCrossRefGoogle Scholar
  22. Ciliberto A, Shah JV (2009) A quantitative systems view of the spindle assembly checkpoint. EMBO J 28(15):2162–2173PubMedCrossRefGoogle Scholar
  23. Clute P, Pines J (1999) Temporal and spatial control of cyclin B1 destruction in metaphase. Nat Cell Biol 1(2):82–87PubMedCrossRefGoogle Scholar
  24. Daum JR, Wren JD, Daniel JJ, Sivakumar S, McAvoy JN, Potapova TA, Gorbsky GJ (2009) Ska3 is required for spindle checkpoint silencing and the maintenance of chromosome cohesion in mitosis. Cur Biol: CB 19(17):1467–1472. doi:10.1016/j.cub.2009.07.017 CrossRefGoogle Scholar
  25. De Antoni A, Pearson CG, Cimini D, Canman JC, Sala V, Nezi L, Mapelli M, Sironi L, Faretta M, Salmon ED, Musacchio A (2005) The Mad1/Mad2 complex as a template for Mad2 activation in the spindle assembly checkpoint. Curr Biol 15(3):214–225PubMedCrossRefGoogle Scholar
  26. DeLuca KF, Lens SMA, Deluca JG (2011) Temporal changes in Hec1 phosphorylation control kinetochore-microtubule attachment stability during mitosis. J Cell Sci 124(Pt 4):622–634. doi:10.1242/jcs.072629 PubMedCrossRefGoogle Scholar
  27. 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(2):267–280PubMedCrossRefGoogle Scholar
  28. 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(6):959–968. doi:10.1083/jcb.201008023 PubMedCrossRefGoogle Scholar
  29. 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(2):241–254. doi:10.1083/jcb.200710019 PubMedCrossRefGoogle Scholar
  30. Emre D, Terracol R, Poncet A, Rahmani Z, Karess RE (2011) A mitotic role for Mad1 beyond the spindle checkpoint. J Cell Sci 124(Pt 10):1664–1671. doi:10.1242/jcs.081216 PubMedCrossRefGoogle Scholar
  31. 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. doi:10.1083/jcb.201111107
  32. Famulski JK, Chan GK (2007) Aurora B kinase-dependent recruitment of hZW10 and hROD to tensionless kinetochores. Curr Biol 17(24):2143–2149. doi:10.1016/j.cub.2007.11.037 PubMedCrossRefGoogle Scholar
  33. Famulski JK, Vos LJ, Rattner JB, Chan GK (2011) Dynein/dynactin-mediated transport of kinetochore components off kinetochores and onto spindle poles induced by nordihydroguaiaretic acid. PLoS One 6(1):e16494. doi:10.1371/journal.pone.0016494 PubMedCrossRefGoogle Scholar
  34. Fava LL, Kaulich M, Nigg EA, Santamaria A (2011) Probing the in vivo function of Mad1:C-Mad2 in the spindle assembly checkpoint. EMBO J. doi:10.1038/emboj.2011.239
  35. 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(10):1265–1271. doi:10.1038/ncb2327 PubMedCrossRefGoogle Scholar
  36. 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(7):4731–4740PubMedGoogle Scholar
  37. Gaglio T, Saredi A, Compton DA (1995) NuMA is required for the organization of microtubules into aster-like mitotic arrays. J Cell Biol 131(3):693–708PubMedCrossRefGoogle Scholar
  38. Gassmann R, Essex A, Hu J-S, Maddox PS, Motegi F, Sugimoto A, O'Rourke SM, Bowerman B, McLeod I, Yates JR, Oegema K, Cheeseman IM, Desai A (2008) A new mechanism controlling kinetochore-microtubule interactions revealed by comparison of two dynein-targeting components: SPDL-1 and the Rod/Zwilch/Zw10 complex. Genes Dev 22(17):2385–2399. doi:10.1101/gad.1687508 PubMedCrossRefGoogle Scholar
  39. 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(9):957–971. doi:10.1101/gad.1886810 PubMedCrossRefGoogle Scholar
  40. Giet R, Glover DM (2001) Drosophila aurora B kinase is required for histone H3 phosphorylation and condensin recruitment during chromosome condensation and to organize the central spindle during cytokinesis. J Cell Biol 152(4):669–682PubMedCrossRefGoogle Scholar
  41. Griffis ER, Stuurman N, Vale RD (2007) Spindly, a novel protein essential for silencing the spindle assembly checkpoint, recruits dynein to the kinetochore. J Cell Biol 177(6):1005–1015. doi:10.1083/jcb.200702062 PubMedCrossRefGoogle Scholar
  42. Habu T, Kim SH, Weinstein J, Matsumoto T (2002) Identification of a MAD2-binding protein, CMT2, and its role in mitosis. EMBO J 21(23):6419–6428PubMedCrossRefGoogle Scholar
  43. Hagan RS, Manak MS, Buch HK, Meier MG, Meraldi P, Shah JV, Sorger PK (2011) p31(comet) acts to ensure timely spindle checkpoint silencing subsequent to kinetochore attachment. Mol Biol Cell 22(22):4236–4246. doi:10.1091/mbc.E11-03-0216 PubMedCrossRefGoogle Scholar
  44. Hanisch A, Silljé HHW, Nigg EA (2006) Timely anaphase onset requires a novel spindle and kinetochore complex comprising Ska1 and Ska2. EMBO J 25(23):5504–5515. doi:10.1038/sj.emboj.7601426 PubMedCrossRefGoogle Scholar
  45. Hardwick KG, Shah JV (2010) Spindle checkpoint silencing: ensuring rapid and concerted anaphase onset. F1000 biology reports 2:55. doi:10.3410/B2-55
  46. Hardwick KG, Weiss E, Luca FC, Winey M, Murray AW (1996) Activation of the budding yeast spindle assembly checkpoint without mitotic spindle disruption. Science 273(5277):953–956PubMedCrossRefGoogle Scholar
  47. 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(5):871–882PubMedCrossRefGoogle Scholar
  48. 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(2):281–294PubMedCrossRefGoogle Scholar
  49. Hegemann B, Hutchins JRA, Hudecz O, Novatchkova M, Rameseder J, Sykora MM, Liu S, Mazanek M, Lénárt P, Hériché J-K, Poser I, Kraut N, Hyman AA, Yaffe MB, Mechtler K, Peters J-M (2011) Systematic phosphorylation analysis of human mitotic protein complexes. Sci Signal 4(198):rs12. doi:10.1126/scisignal.2001993 PubMedCrossRefGoogle Scholar
  50. Hengeveld RCC, Hertz NT, Vromans MJM, Zhang C, Burlingame AL, Shokat KM, Lens SMA (2012) Development of a chemical genetic approach for human Aurora B kinase identifies novel substrates of the chromosomal passenger complex. Molecular & Cellular Proteomics. doi:10.1074/mcp.M111.013912
  51. 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(1):25–34. doi:10.1083/jcb.201002133 PubMedCrossRefGoogle Scholar
  52. Holt SV, Vergnolle MAS, Hussein D, Wozniak MJ, Allan VJ, Taylor SS (2005) Silencing Cenp-F weakens centromeric cohesion, prevents chromosome alignment and activates the spindle checkpoint. J Cell Sci 118(Pt 20):4889–4900. doi:10.1242/jcs.02614 PubMedCrossRefGoogle Scholar
  53. Hori T, Haraguchi T, Hiraoka Y, Kimura H, Fukagawa T (2003) Dynamic behavior of Nuf2-Hec1 complex that localizes to the centrosome and centromere and is essential for mitotic progression in vertebrate cells. J Cell Sci 116(Pt 16):3347–3362PubMedCrossRefGoogle Scholar
  54. Howell BJ, Hoffman DB, Fang G, Murray AW, Salmon ED (2000) Visualization of Mad2 dynamics at kinetochores, along spindle fibers, and at spindle poles in living cells. J Cell Biol 150(6):1233–1250PubMedCrossRefGoogle Scholar
  55. 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(7):1159–1172. doi:10.1083/jcb.200105093 PubMedCrossRefGoogle Scholar
  56. 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(11):953–964PubMedCrossRefGoogle Scholar
  57. Hoyt MA, Totis L, Roberts BT (1991) S. cerevisiae genes required for cell cycle arrest in response to loss of microtubule function. Cell 66(3):507–517PubMedCrossRefGoogle Scholar
  58. 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(3):279–291PubMedCrossRefGoogle Scholar
  59. Jablonski SA, Chan GK, Cooke CA, Earnshaw WC, Yen TJ (1998) The hBUB1 and hBUBR1 kinases sequentially assemble onto kinetochores during prophase with hBUBR1 concentrating at the kinetochore plates in mitosis. Chromosoma 107(6–7):386–396PubMedCrossRefGoogle Scholar
  60. Jelluma N, Brenkman AB, van den Broek NJF, Cruijsen CWA, van Osch MHJ, Lens SMA, Medema RH, Kops GJPL (2008) Mps1 phosphorylates Borealin to control Aurora B activity and chromosome alignment. Cell 132(2):233–246. doi:10.1016/j.cell.2007.11.046 PubMedCrossRefGoogle Scholar
  61. Jelluma N, Dansen TB, Sliedrecht T, Kwiatkowski NP, Kops GJPL (2010) Release of Mps1 from kinetochores is crucial for timely anaphase onset. J Cell Biol 191(2):281–290. doi:10.1083/jcb.201003038 PubMedCrossRefGoogle Scholar
  62. 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(22):4227–4235. doi:10.1091/mbc.E11-05-0389 PubMedCrossRefGoogle Scholar
  63. Johnson VL, Scott MIF, 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(Pt 8):1577–1589. doi:10.1242/jcs.01006 PubMedCrossRefGoogle Scholar
  64. 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(5):841–847PubMedCrossRefGoogle Scholar
  65. Kang YH, Park J-E, Yu L-R, Soung N-K, Yun S-M, Bang JK, Seong Y-S, 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(3):409–422. doi:10.1016/j.molcel.2006.10.016 PubMedCrossRefGoogle Scholar
  66. Kapoor TM, Mayer TU, Coughlin ML, Mitchison TJ (2000) Probing spindle assembly mechanisms with monastrol, a small molecule inhibitor of the mitotic kinesin, Eg5. J Cell Biol 150(5):975–988PubMedCrossRefGoogle Scholar
  67. Kasuboski JM, Bader JR, Vaughan PS, Tauhata SBF, 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(18):3318–3330. doi:10.1091/mbc.E11-03-0213 PubMedCrossRefGoogle Scholar
  68. Kelly AE, Funabiki H (2009) Correcting aberrant kinetochore microtubule attachments: an Aurora B-centric view. Curr Opin Cell Biol 21(1):51–58. doi:10.1016/ PubMedCrossRefGoogle Scholar
  69. 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(8):1099–1110. doi:10.1038/emboj.2009.62 PubMedCrossRefGoogle Scholar
  70. Kettenbach AN, Schweppe DK, Faherty BK, Pechenick D, Pletnev AA, Gerber SA (2011) Quantitative phosphoproteomics identifies substrates and functional modules of Aurora and Polo-like kinase activities in mitotic cells. Sci Signal 4(179):rs5. doi:10.1126/scisignal.2001497 PubMedCrossRefGoogle Scholar
  71. Khodjakov A, Pines J (2010) Centromere tension: a divisive issue. Nat Cell Biol 12(10):919–923. doi:10.1038/ncb1010-919 PubMedCrossRefGoogle Scholar
  72. Kim S, Yu H (2011) Mutual regulation between the spindle checkpoint and APC/C. Semin Cell Dev Biol 22(6):551–558. doi:10.1016/j.semcdb.2011.03.008 PubMedCrossRefGoogle Scholar
  73. King JM, Hays TS, Nicklas RB (2000) Dynein is a transient kinetochore component whose binding is regulated by microtubule attachment, not tension. J Cell Biol 151(4):739–748PubMedCrossRefGoogle Scholar
  74. King EMJ, Rachidi N, Morrice N, Hardwick KG, Stark MJR (2007) Ipl1p-dependent phosphorylation of Mad3p is required for the spindle checkpoint response to lack of tension at kinetochores. Genes Dev 21(10):1163–1168. doi:10.1101/gad.431507 PubMedCrossRefGoogle Scholar
  75. 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(5):663–676. doi:10.1016/j.devcel.2007.09.005 PubMedCrossRefGoogle Scholar
  76. 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(5):998–1011. doi:10.1128/MCB.00815-10 PubMedCrossRefGoogle Scholar
  77. Klebig C, Korinth D, Meraldi P (2009) Bub1 regulates chromosome segregation in a kinetochore-independent manner. J Cell Biol 185(5):841–858. doi:10.1083/jcb.200902128 PubMedCrossRefGoogle Scholar
  78. Koch A, Krug K, Pengelley S, Macek B, Hauf S (2011) Mitotic substrates of the kinase aurora with roles in chromatin regulation identified through quantitative phosphoproteomics of fission yeast. Sci Signal 4(179):rs6. doi:10.1126/scisignal.2001588 PubMedCrossRefGoogle Scholar
  79. Kops GJPL, Kim Y, Weaver BAA, Mao Y, McLeod I, Yates JR, Tagaya M, Cleveland DW (2005) ZW10 links mitotic checkpoint signaling to the structural kinetochore. J Cell Biol 169(1):49–60. doi:10.1083/jcb.200411118 PubMedCrossRefGoogle Scholar
  80. Kops GJPL, van der Voet M, Manak MS, van Osch MHJ, Naini SM, Brear A, McLeod IX, Hentschel DM, Yates JR, Van Den Heuvel S, Shah JV (2010) APC16 is a conserved subunit of the anaphase-promoting complex/cyclosome. J Cell Sci 123(Pt 10):1623–1633. doi:10.1242/jcs.061549 PubMedCrossRefGoogle Scholar
  81. Krenn V, Wehenkel A, Li X, Santaguida S, Musacchio A (2012) Structural analysis reveals features of the spindle checkpoint kinase Bub1-kinetochore subunit Knl1 interaction. The Journal of Cell Biology. doi:10.1083/jcb.201110013Google Scholar
  82. Kulukian A, Han J, Cleveland D (2009) Unattached kinetochores catalyze production of an anaphase inhibitor that requires a Mad2 template to prime Cdc20 for BubR1 binding. Dev Cell 16(1):105–117. doi:10.1016/j.devcel.2008.11.005 PubMedCrossRefGoogle Scholar
  83. Kwiatkowski N, Jelluma N, Filippakopoulos P, Soundararajan M, Manak MS, Kwon M, Choi HG, Sim T, Deveraux QL, Rottmann S, Pellman D, Shah JV, Kops GJPL, Knapp S, Gray NS (2010) Small-molecule kinase inhibitors provide insight into Mps1 cell cycle function. Nat Chem Biol 6(5):359–368. doi:10.1038/nchembio.345 PubMedCrossRefGoogle Scholar
  84. Lampson MA, Cheeseman IM (2011) Sensing centromere tension: Aurora B and the regulation of kinetochore function. Trends Cell Biol 21(3):133–140. doi:10.1016/j.tcb.2010.10.007 PubMedCrossRefGoogle Scholar
  85. Lampson MA, Renduchitala K, Khodjakov A, Kapoor TM (2004) Correcting improper chromosome-spindle attachments during cell division. Nat Cell Biol 6(3):232–237PubMedCrossRefGoogle Scholar
  86. Lara-Gonzalez P, Scott MIF, 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(Pt 24):4332–4345. doi:10.1242/jcs.094763 PubMedCrossRefGoogle Scholar
  87. Li R, Murray AW (1991) Feedback control of mitosis in budding yeast. Cell 66(3):519–531PubMedCrossRefGoogle Scholar
  88. Li J, Lee W-L, Cooper JA (2005) NudEL targets dynein to microtubule ends through LIS1. Nat Cell Biol 7(7):686–690. doi:10.1038/ncb1273 PubMedCrossRefGoogle Scholar
  89. Li Y, Yu W, Liang Y, Zhu X (2007) Kinetochore dynein generates a poleward pulling force to facilitate congression and full chromosome alignment. Cell Res 17(8):701–712. doi:10.1038/cr.2007.65 PubMedCrossRefGoogle Scholar
  90. Liao H, Winkfein RJ, Mack G, Rattner JB, Yen TJ (1995) CENP-F is a protein of the nuclear matrix that assembles onto kinetochores at late G2 and is rapidly degraded after mitosis. J Cell Biol 130(3):507–518PubMedCrossRefGoogle Scholar
  91. Liu D, Vader G, Vromans MJM, Lampson MA, Lens SMA (2009) Sensing chromosome biorientation by spatial separation of aurora B kinase from kinetochore substrates. Sci (New York, NY) 323(5919):1350–1353. doi:10.1126/science.1167000 CrossRefGoogle Scholar
  92. 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(6):809–820. doi:10.1083/jcb.201001006 PubMedCrossRefGoogle Scholar
  93. 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(4):1798–1813. doi:10.1091/mbc.E07-07-0633 PubMedCrossRefGoogle Scholar
  94. London N, Ceto S, Ranish JA, Biggins S (2012) Phosphoregulation of Spc105 by Mps1 and PP1 regulates Bub1 localization to kinetochores. Curr Biol: CB 22(10):900–906. doi:10.1016/j.cub.2012.03.052 PubMedCrossRefGoogle Scholar
  95. Luo X, Yu H (2008) Protein metamorphosis: the two-state behavior of Mad2. Struct/Fold Des 16(11):1616–1625. doi:10.1016/j.str.2008.10.002 CrossRefGoogle Scholar
  96. Luo X, Tang Z, Rizo J, Yu H (2002) The Mad2 spindle checkpoint protein undergoes similar major conformational changes upon binding to either Mad1 or Cdc20. Mol Cell 9(1):59–71PubMedCrossRefGoogle Scholar
  97. Maciejowski J, George KA, Terret M-E, 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(1):89–100. doi:10.1083/jcb.201001050 PubMedCrossRefGoogle Scholar
  98. Mack GJ, Compton DA (2001) Analysis of mitotic microtubule-associated proteins using mass spectrometry identifies astrin, a spindle-associated protein. Proc Natl Acad Sci U S A 98(25):14434–14439. doi:10.1073/pnas.261371298 PubMedCrossRefGoogle Scholar
  99. Maiato H, Fairley EAL, Rieder CL, Swedlow JR, Sunkel CE, Earnshaw WC (2003) Human CLASP1 is an outer kinetochore component that regulates spindle microtubule dynamics. Cell 113(7):891–904PubMedCrossRefGoogle Scholar
  100. Maldonado M, Kapoor TM (2011) Constitutive Mad1 targeting to kinetochores uncouples checkpoint signalling from chromosome biorientation. Nat Cell Biol. doi:doi:10.1038/ncb2223
  101. 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(20):3531–3543. doi:10.1038/emboj.2010.230 PubMedCrossRefGoogle Scholar
  102. Mapelli M, Musacchio A (2007) MAD contortions: conformational dimerization boosts spindle checkpoint signaling. Curr Opin Struct Biol 17(6):716–725. doi:10.1016/ PubMedCrossRefGoogle Scholar
  103. Mapelli M, Filipp FV, Rancati G, Massimiliano L, Nezi L, Stier G, Hagan RS, Confalonieri S, Piatti S, Sattler M, Musacchio A (2006) Determinants of conformational dimerization of Mad2 and its inhibition by p31comet. EMBO J 25(6):1273–1284PubMedCrossRefGoogle Scholar
  104. Maresca TJ, Salmon ED (2009) Intrakinetochore stretch is associated with changes in kinetochore phosphorylation and spindle assembly checkpoint activity. J Cell Biol 184(3):373–381. doi:10.1083/jcb.200808130 PubMedCrossRefGoogle Scholar
  105. Maresca TJ, Salmon ED (2010) Welcome to a new kind of tension: translating kinetochore mechanics into a wait-anaphase signal. J Cell Sci 123(Pt 6):825–835. doi:10.1242/jcs.064790 PubMedCrossRefGoogle Scholar
  106. Martin-Lluesma S, Stucke VM, Nigg EA (2002) Role of Hec1 in spindle checkpoint signaling and kinetochore recruitment of Mad1/Mad2. Science 297(5590):2267–2270PubMedCrossRefGoogle Scholar
  107. 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(6):542–547. doi:10.1101/gad.184184.111 PubMedCrossRefGoogle Scholar
  108. McCleland ML, Gardner RD, Kallio MJ, Daum JR, Gorbsky GJ, Burke DJ, Stukenberg PT (2003) The highly conserved Ndc80 complex is required for kinetochore assembly, chromosome congression, and spindle checkpoint activity. Genes Dev 17(1):101–114. doi:10.1101/gad.1040903 PubMedCrossRefGoogle Scholar
  109. McIntosh JR (1991) Structural and mechanical control of mitotic progression. Cold Spring Harb Symp Quant Biol 56:613–619PubMedCrossRefGoogle Scholar
  110. Meadows JC, Shepperd LA, Vanoosthuyse V, Lancaster TC, Sochaj AM, Buttrick GJ, Hardwick KG, Millar JBA (2011) Spindle checkpoint silencing requires association of PP1 to both Spc7 and kinesin-8 motors. Dev Cell 20(6):739–750. doi:10.1016/j.devcel.2011.05.008 PubMedCrossRefGoogle Scholar
  111. Meraldi P, Sorger PK (2005) A dual role for Bub1 in the spindle checkpoint and chromosome congression. EMBO J 24(8):1621–1633PubMedCrossRefGoogle Scholar
  112. Miniowitz-Shemtov S, Eytan E, Ganoth D, Sitry-Shevah D, Dumin E, Hershko A (2012) Role of phosphorylation of Cdc20 in p31comet-stimulated disassembly of the mitotic checkpoint complex. Proc Natl Acad Sci U S A. doi:10.1073/pnas.1204081109
  113. 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(Pt 16):3639–3652PubMedCrossRefGoogle Scholar
  114. Murata-Hori M, Tatsuka M, Wang Y-L (2002) Probing the dynamics and functions of aurora B kinase in living cells during mitosis and cytokinesis. Mol Biol Cell 13(4):1099–1108. doi:10.1091/mbc.01-09-0467 PubMedCrossRefGoogle Scholar
  115. Murnion ME, Adams RR, Callister DM, Allis CD, Earnshaw WC, Swedlow JR (2001) Chromatin-associated protein phosphatase 1 regulates aurora-B and histone H3 phosphorylation. J Biol Chem 276(28):26656–26665. doi:10.1074/jbc.M102288200 PubMedCrossRefGoogle Scholar
  116. Musacchio A, Salmon ED (2007) The spindle-assembly checkpoint in space and time. Nat Rev Mol Cell Biol 8(5):379–393PubMedCrossRefGoogle Scholar
  117. Nezi L, Musacchio A (2009) Sister chromatid tension and the spindle assembly checkpoint. Curr Opin Cell Biol 21(6):785–795. doi:10.1016/ PubMedCrossRefGoogle Scholar
  118. Niethammer M, Smith DS, Ayala R, Peng J, Ko J, Lee MS, Morabito M, Tsai LH (2000) NUDEL is a novel Cdk5 substrate that associates with LIS1 and cytoplasmic dynein. Neuron 28(3):697–711PubMedCrossRefGoogle Scholar
  119. Nishihashi A, Haraguchi T, Hiraoka Y, Ikemura T, Regnier V, Dodson H, Earnshaw WC, Fukagawa T (2002) CENP-I is essential for centromere function in vertebrate cells. Dev Cell 2(4):463–476PubMedCrossRefGoogle Scholar
  120. 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 Biolo 6(11):1135–1141. doi:10.1038/ncb1187 CrossRefGoogle Scholar
  121. 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(5):653–659. doi:10.1242/jcs.059501 PubMedCrossRefGoogle Scholar
  122. Petersen J, Hagan IM (2003) S. pombe aurora kinase/survivin is required for chromosome condensation and the spindle checkpoint attachment response. Curr Biol 13(7):590–597PubMedCrossRefGoogle Scholar
  123. Pines J (2011) Cubism and the cell cycle: the many faces of the APC/C. Nature Reviews Molecular Cell Biology. doi:10.1038/nrm3132Google Scholar
  124. 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(7):2648–2660. doi:10.1128/MCB.26.7.2648-2660.2006 PubMedCrossRefGoogle Scholar
  125. 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(1):78–83. doi:10.1038/ncb1341 PubMedCrossRefGoogle Scholar
  126. Pinsky BA, Nelson CR, Biggins S (2009) Protein phosphatase 1 regulates exit from the spindle checkpoint in budding yeast. Curr Biol 19(14):1182–1187. doi:10.1016/j.cub.2009.06.043 PubMedCrossRefGoogle Scholar
  127. 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(1):61–74. doi:10.1083/jcb.200912046 PubMedCrossRefGoogle Scholar
  128. Raaijmakers JA, Tanenbaum ME, Maia AF, Medema RH (2009) RAMA1 is a novel kinetochore protein involved in kinetochore-microtubule attachment. J Cell Sci 122(Pt 14):2436–2445. doi:10.1242/jcs.051912 PubMedCrossRefGoogle Scholar
  129. Rancati G, Crispo V, Lucchini G, Piatti S (2005) Mad3/BubR1 phosphorylation during spindle checkpoint activation depends on both Polo and Aurora kinases in budding yeast. Cell cycle (Georgetown, Tex) 4(7):972–980CrossRefGoogle Scholar
  130. Reddy SK, Rape M, Margansky WA, Kirschner MW (2007) Ubiquitination by the anaphase-promoting complex drives spindle checkpoint inactivation. Nature 446(7138):921–925. doi:10.1038/nature05734 PubMedCrossRefGoogle Scholar
  131. 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(5):1301–1310PubMedCrossRefGoogle Scholar
  132. 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(4):941–948PubMedCrossRefGoogle Scholar
  133. Rosenberg JS, Cross FR, Funabiki H (2011) KNL1/Spc105 recruits PP1 to silence the spindle assembly checkpoint. Curr Biol: CB 21(11):942–947. doi:10.1016/j.cub.2011.04.011 PubMedCrossRefGoogle Scholar
  134. Ruchaud S, Carmena M, Earnshaw WC (2007) Chromosomal passengers: conducting cell division. Nat Rev Mol Cell Biol 8(10):798–812. doi:10.1038/nrm2257 PubMedCrossRefGoogle Scholar
  135. 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. Current biology: CB 21(13):1158–1165. doi:10.1016/j.cub.2011.06.015 PubMedCrossRefGoogle Scholar
  136. Santaguida S, Tighe A, D'Alise AM, Taylor SS, Musacchio A (2010) Dissecting the role of MPS1 in chromosome biorientation and the spindle checkpoint through the small molecule inhibitor reversine. J Cell Biol 190(1):73–87. doi:10.1083/jcb.201001036 PubMedCrossRefGoogle Scholar
  137. 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(8):1508–1519. doi:10.1038/emboj.2011.70 PubMedCrossRefGoogle Scholar
  138. Sasaki S, Shionoya A, Ishida M, Gambello MJ, Yingling J, Wynshaw-Boris A, Hirotsune S (2000) A LIS1/NUDEL/cytoplasmic dynein heavy chain complex in the developing and adult nervous system. Neuron 28(3):681–696. doi:10.1016/S0896-6273(00)00146-X PubMedCrossRefGoogle Scholar
  139. Saurin AT, van der Waal MS, Medema RH, Lens SMA, Kops GJPL (2011) Aurora B potentiates Mps1 activation to ensure rapid checkpoint establishment at the onset of mitosis. Nat Commun 2:316. doi:10.1038/ncomms1319 PubMedCrossRefGoogle Scholar
  140. Scaërou F, Starr DA, Piano F, Papoulas O, Karess RE, Goldberg ML (2001) The ZW10 and Rough Deal checkpoint proteins function together in a large, evolutionarily conserved complex targeted to the kinetochore. J Cell Sci 114(Pt 17):3103–3114PubMedGoogle Scholar
  141. 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(2):269–280. doi:10.1083/jcb.201006129 PubMedCrossRefGoogle Scholar
  142. 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(11):942–952PubMedGoogle Scholar
  143. Shepperd LA, Meadows JC, Sochaj AM, Lancaster TC, Zou J, Buttrick GJ, Rappsilber J, Hardwick KG, Millar JBA (2012) Phosphodependent recruitment of Bub1 and Bub3 to Spc7/KNL1 by Mph1 kinase maintains the spindle checkpoint. Curr Biol: CB 22(10):891–899. doi:10.1016/j.cub.2012.03.051 PubMedCrossRefGoogle Scholar
  144. Simonetta M, Manzoni R, Mosca R, Mapelli M, Massimiliano L, Vink M, Novak B, Musacchio A, Ciliberto A (2009) The influence of catalysis on Mad2 activation dynamics. Plos Biol 7(1):e10. doi:10.1371/journal.pbio.1000010 PubMedCrossRefGoogle Scholar
  145. 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 U S A 98(8):4492–4497PubMedCrossRefGoogle Scholar
  146. Sliedrecht T, Zhang C, Shokat KM, Kops GJPL (2010) Chemical genetic inhibition of Mps1 in stable human cell lines reveals novel aspects of Mps1 function in mitosis. PLoS One 5(4):e10251. doi:10.1371/journal.pone.0010251 PubMedCrossRefGoogle Scholar
  147. Starr DA, Williams BC, Hays TS, Goldberg ML (1998) ZW10 helps recruit dynactin and dynein to the kinetochore. J Cell Biol 142(3):763–774PubMedCrossRefGoogle Scholar
  148. Stegmeier F, Rape M, Draviam VM, Nalepa G, Sowa ME, Ang XL, McDonald ER, 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(7138):876–881. doi:10.1038/nature05694 PubMedCrossRefGoogle Scholar
  149. Stehman SA, Chen Y, McKenney RJ, Vallee RB (2007) NudE and NudEL are required for mitotic progression and are involved in dynein recruitment to kinetochores. J Cell Biol 178(4):583–594. doi:10.1083/jcb.200610112 PubMedCrossRefGoogle Scholar
  150. Stucke VM, Baumann C, Nigg EA (2004) Kinetochore localization and microtubule interaction of the human spindle checkpoint kinase Mps1. Chromosoma 113(1):1–15PubMedCrossRefGoogle Scholar
  151. 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(5):925–936PubMedCrossRefGoogle Scholar
  152. Tanaka TU, Rachidi N, Janke C, Pereira G, Galova M, Schiebel E, Stark MJR, Nasmyth K (2002) Evidence that the Ipl1-Sli15 (Aurora kinase-INCENP) complex promotes chromosome biorientation by altering kinetochore-spindle pole connections. Cell 108(3):317–329PubMedCrossRefGoogle Scholar
  153. Tanenbaum ME, Macůrek L, Galjart N, Medema RH (2008) Dynein, Lis1 and CLIP-170 counteract Eg5-dependent centrosome separation during bipolar spindle assembly. EMBO J 27(24):3235–3245. doi:10.1038/emboj.2008.242 PubMedCrossRefGoogle Scholar
  154. 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(3):387–397PubMedCrossRefGoogle Scholar
  155. 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):1–11PubMedCrossRefGoogle Scholar
  156. Taylor SS, Hussein D, Wang Y, Elderkin S, Morrow CJ (2001) Kinetochore localisation and phosphorylation of the mitotic checkpoint components Bub1 and BubR1 are differentially regulated by spindle events in human cells. J Cell Sci 114(Pt 24):4385–4395PubMedGoogle Scholar
  157. 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. Proceedings of the National Academy of Sciences:1-6. doi:10.1073/pnas.1100023108
  158. Theis M, Slabicki M, Junqueira M, Paszkowski-Rogacz M, Sontheimer J, Kittler R, Heninger A-K, Glatter T, Kruusmaa K, Poser I, Hyman AA, Pisabarro MT, Gstaiger M, Aebersold R, Shevchenko A, Buchholz F (2009) Comparative profiling identifies C13orf3 as a component of the Ska complex required for mammalian cell division. EMBO J 28(10):1453–1465. doi:10.1038/emboj.2009.114 PubMedCrossRefGoogle Scholar
  159. Tirnauer JS, Canman JC, Salmon ED, Mitchison TJ (2002) EB1 targets to kinetochores with attached, polymerizing microtubules. Mol Biol Cell 13(12):4308–4316. doi:10.1091/mbc.E02-04-0236 PubMedCrossRefGoogle Scholar
  160. 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(1):107–117. doi:10.1091/mbc.E02-07-0376 PubMedCrossRefGoogle Scholar
  161. Uchida KSK, Takagaki K, Kumada K, Hirayama Y, Noda T, Hirota T (2009) Kinetochore stretching inactivates the spindle assembly checkpoint. J Cell Biol 184(3):383–390. doi:10.1083/jcb.200811028 PubMedCrossRefGoogle Scholar
  162. Vanoosthuyse V, Hardwick KG (2009) A novel protein phosphatase 1-dependent spindle checkpoint silencing mechanism. Curr Biol 19(14):1176–1181. doi:10.1016/j.cub.2009.05.060 PubMedCrossRefGoogle Scholar
  163. Varetti G, Guida C, Santaguida S, Chiroli E, Musacchio A (2011) Homeostatic control of mitotic arrest. Mol Cell 44(5):710–720. doi:10.1016/j.molcel.2011.11.014 PubMedCrossRefGoogle Scholar
  164. Vergnolle MAS, Taylor SS (2007) Cenp-F links kinetochores to Ndel1/Nde1/Lis1/dynein microtubule motor complexes. Curr Biol 17(13):1173–1179. doi:10.1016/j.cub.2007.05.077 PubMedCrossRefGoogle Scholar
  165. 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(10):4584–4596PubMedCrossRefGoogle Scholar
  166. Vink M, Simonetta M, Transidico P, Ferrari K, Mapelli M, De Antoni A, Massimiliano L, Ciliberto A, Faretta M, Salmon ED, Musacchio A (2006) In vitro FRAP identifies the minimal requirements for Mad2 kinetochore dynamics. Curr Biol 16(8):755–766PubMedCrossRefGoogle Scholar
  167. 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(2):169–179. doi:10.1007/s00412-007-0135-3 PubMedCrossRefGoogle Scholar
  168. 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(4):672–684. doi:10.1016/j.cell.2009.03.035 PubMedCrossRefGoogle Scholar
  169. 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(9):3029–3041. doi:10.1091/mbc.E02-04-0203 PubMedCrossRefGoogle Scholar
  170. Waters JC, Chen RH, Murray AW, Salmon ED (1998) Localization of Mad2 to kinetochores depends on microtubule attachment, not tension. J Cell Biol 141(5):1181–1191PubMedCrossRefGoogle Scholar
  171. Weiss E, Winey M (1996) The Saccharomyces cerevisiae spindle pole body duplication gene MPS1 is part of a mitotic checkpoint. J Cell Biol 132(1–2):111–123PubMedCrossRefGoogle Scholar
  172. Welburn JPI, Vleugel M, Liu D, Yates JR, Lampson MA, Fukagawa T, Cheeseman IM (2010) Aurora B phosphorylates spatially distinct targets to differentially regulate the kinetochore-microtubule interface. Mol Cell 38(3):383–392. doi:10.1016/j.molcel.2010.02.034 PubMedCrossRefGoogle Scholar
  173. Westhorpe FG, Tighe A, Lara-Gonzalez P, Taylor SS (2011) p31comet-mediated extraction of Mad2 from the MCC promotes efficient mitotic exit. Journal of Cell Science. doi:10.1242/jcs.093286
  174. Whyte J, Bader JR, Tauhata SBF, Raycroft M, Hornick J, Pfister KK, Lane WS, Chan GK, Hinchcliffe EH, Vaughan PS, Vaughan KT (2008) Phosphorylation regulates targeting of cytoplasmic dynein to kinetochores during mitosis. J Cell Biol 183(5):819–834. doi:10.1083/jcb.200804114 PubMedCrossRefGoogle Scholar
  175. Williams BC, Gatti M, Goldberg ML (1996) Bipolar spindle attachments affect redistributions of ZW10, a Drosophila centromere/kinetochore component required for accurate chromosome segregation. J Cell Biol 134(5):1127–1140PubMedCrossRefGoogle Scholar
  176. Williams BC, Li Z, Liu S, Williams EV, Leung G, Yen TJ, Goldberg ML (2003) Zwilch, a new component of the ZW10/ROD complex required for kinetochore functions. Mol Biol Cell 14(4):1379–1391. doi:10.1091/mbc.E02-09-0624 PubMedCrossRefGoogle Scholar
  177. Wojcik E, Basto R, Serr M, Scaërou F, Karess R, Hays T (2001) Kinetochore dynein: its dynamics and role in the transport of the rough deal checkpoint protein. Nat Cell Biol 3(11):1001–1007. doi:10.1038/ncb1101-1001 PubMedCrossRefGoogle Scholar
  178. Xia G, Luo X, Habu T, Rizo J, Matsumoto T, Yu H (2004) Conformation-specific binding of p31(comet) antagonizes the function of Mad2 in the spindle checkpoint. EMBO J 23(15):3133–3143PubMedCrossRefGoogle Scholar
  179. Yamaguchi S, Decottignies A, Nurse P (2003) Function of Cdc2p-dependent Bub1p phosphorylation and Bub1p kinase activity in the mitotic and meiotic spindle checkpoint. EMBO J 22(5):1075–1087. doi:10.1093/emboj/cdg100 PubMedCrossRefGoogle Scholar
  180. Yamamoto TG, Watanabe S, Essex A, Kitagawa R (2008) SPDL-1 functions as a kinetochore receptor for MDF-1 in Caenorhabditis elegans. J Cell Biol 183(2):187–194. doi:10.1083/jcb.200805185 PubMedCrossRefGoogle Scholar
  181. Yang M, Li B, Tomchick DR, Machius M, Rizo J, Yu H, Luo X (2007a) p31(comet) blocks Mad2 activation through structural mimicry. Cell 131(4):744–755. doi:10.1016/j.cell.2007.08.048 PubMedCrossRefGoogle Scholar
  182. Yang Z, Tulu US, Wadsworth P, Rieder CL (2007b) Kinetochore dynein is required for chromosome motion and congression independent of the spindle checkpoint. Curr Biol 17(11):973–980. doi:10.1016/j.cub.2007.04.056 PubMedCrossRefGoogle Scholar
  183. Yasui Y, Urano T, Kawajiri A, K-i N, Tatsuka M, Saya H, Furukawa K, Takahashi T, Izawa I, Inagaki M (2004) Autophosphorylation of a newly identified site of Aurora-B is indispensable for cytokinesis. J Biol Chem 279(13):12997–13003. doi:10.1074/jbc.M311128200 PubMedCrossRefGoogle Scholar
  184. Yen TJ, Compton DA, Wise D, Zinkowski RP, Brinkley BR, Earnshaw WC, Cleveland DW (1991) CENP-E, a novel human centromere-associated protein required for progression from metaphase to anaphase. EMBO J 10(5):1245–1254PubMedGoogle Scholar
  185. Zirkle RE (1970) Ultraviolet-microbeam irradiation of newt-cell cytoplasm: spindle destruction, false anaphase, and delay of true anaphase. Radiat Res 41(3):516–537PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2012

Authors and Affiliations

  1. 1.Department of Medical Oncology and Department of Molecular Cancer ResearchUniversity Medical Center UtrechtUtrechtThe Netherlands
  2. 2.Department of Systems Biology, Harvard Medical School and Renal DivisionBrigham and Women’s HospitalBostonUSA
  3. 3.Medical Oncology & Molecular Cancer ResearchUniversity Medical Center UtrechtUtrechtThe Netherlands
  4. 4.Department of Systems BiologyHarvard Medical SchoolBostonUSA

Personalised recommendations