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

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Abstract

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.

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Abbreviations

SAC:

Spindle assembly checkpoint

MT:

Microtubule

RZZ:

Rod/Zw10/Zwilch

CENP:

Centromere protein

KMN:

Knl1/Mis12/Ndc80 complex

CPC:

Chromosome passenger complex

TAP:

Tandem affinity purification

Cdk1:

Cyclin-dependent kinase 1

APC/C:

Anaphase promoting complex/cyclosome

MCC:

Mitotic checkpoint complex

DIC:

Dynein intermediate chain

References

  • 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):83–93

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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):424–429

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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):56–61

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • 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):3927–3939

    Article  PubMed  CAS  Google Scholar 

  • 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):4870–4875

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • Chao WCH, Kulkarni K, Zhang Z, Kong EH, Barford D (2012) Structure of the mitotic checkpoint complex. Nature. doi:10.1038/nature10896

  • 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):2255–2268

    Article  PubMed  CAS  Google Scholar 

  • Chen RH, Waters JC, Salmon ED, Murray AW (1996) Association of spindle assembly checkpoint component XMAD2 with unattached kinetochores. Science 274(5285):242–246

    Article  PubMed  CAS  Google Scholar 

  • Chen RH, Shevchenko A, Mann M, Murray AW (1998) Spindle checkpoint protein Xmad1 recruits Xmad2 to unattached kinetochores. J Cell Biol 143(2):283–295

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • Ciliberto A, Shah JV (2009) A quantitative systems view of the spindle assembly checkpoint. EMBO J 28(15):2162–2173

    Article  PubMed  CAS  Google Scholar 

  • Clute P, Pines J (1999) Temporal and spatial control of cyclin B1 destruction in metaphase. Nat Cell Biol 1(2):82–87

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • 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):214–225

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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):267–280

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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):4731–4740

    PubMed  CAS  Google Scholar 

  • 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):693–708

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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):669–682

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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):6419–6428

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • Hardwick KG, Shah JV (2010) Spindle checkpoint silencing: ensuring rapid and concerted anaphase onset. F1000 biology reports 2:55. doi:10.3410/B2-55

  • 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):953–956

    Article  PubMed  CAS  Google Scholar 

  • 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):871–882

    Article  PubMed  CAS  Google Scholar 

  • 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):281–294

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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):3347–3362

    Article  PubMed  CAS  Google Scholar 

  • 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):1233–1250

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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):953–964

    Article  PubMed  CAS  Google Scholar 

  • 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):507–517

    Article  PubMed  CAS  Google Scholar 

  • 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):279–291

    Article  PubMed  CAS  Google Scholar 

  • 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):386–396

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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):841–847

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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):975–988

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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/j.ceb.2009.01.004

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • Khodjakov A, Pines J (2010) Centromere tension: a divisive issue. Nat Cell Biol 12(10):919–923. doi:10.1038/ncb1010-919

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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):739–748

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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.201110013

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • Lampson MA, Renduchitala K, Khodjakov A, Kapoor TM (2004) Correcting improper chromosome-spindle attachments during cell division. Nat Cell Biol 6(3):232–237

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • Li R, Murray AW (1991) Feedback control of mitosis in budding yeast. Cell 66(3):519–531

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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):507–518

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • 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):59–71

    Article  PubMed  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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):891–904

    Article  PubMed  CAS  Google Scholar 

  • Maldonado M, Kapoor TM (2011) Constitutive Mad1 targeting to kinetochores uncouples checkpoint signalling from chromosome biorientation. Nat Cell Biol. doi:doi:10.1038/ncb2223

  • 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

    Article  PubMed  CAS  Google Scholar 

  • Mapelli M, Musacchio A (2007) MAD contortions: conformational dimerization boosts spindle checkpoint signaling. Curr Opin Struct Biol 17(6):716–725. doi:10.1016/j.sbi.2007.08.011

    Article  PubMed  CAS  Google Scholar 

  • 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):1273–1284

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • Martin-Lluesma S, Stucke VM, Nigg EA (2002) Role of Hec1 in spindle checkpoint signaling and kinetochore recruitment of Mad1/Mad2. Science 297(5590):2267–2270

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • McIntosh JR (1991) Structural and mechanical control of mitotic progression. Cold Spring Harb Symp Quant Biol 56:613–619

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • Meraldi P, Sorger PK (2005) A dual role for Bub1 in the spindle checkpoint and chromosome congression. EMBO J 24(8):1621–1633

    Article  PubMed  CAS  Google Scholar 

  • 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

  • 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):3639–3652

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • Musacchio A, Salmon ED (2007) The spindle-assembly checkpoint in space and time. Nat Rev Mol Cell Biol 8(5):379–393

    Article  PubMed  CAS  Google Scholar 

  • Nezi L, Musacchio A (2009) Sister chromatid tension and the spindle assembly checkpoint. Curr Opin Cell Biol 21(6):785–795. doi:10.1016/j.ceb.2009.09.007

    Article  PubMed  CAS  Google Scholar 

  • 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):697–711

    Article  PubMed  CAS  Google Scholar 

  • 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):463–476

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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):590–597

    Article  PubMed  CAS  Google Scholar 

  • Pines J (2011) Cubism and the cell cycle: the many faces of the APC/C. Nature Reviews Molecular Cell Biology. doi:10.1038/nrm3132

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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):972–980

    Article  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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):1301–1310

    Article  PubMed  CAS  Google Scholar 

  • 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):941–948

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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):3103–3114

    PubMed  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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):942–952

    PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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):4492–4497

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • Starr DA, Williams BC, Hays TS, Goldberg ML (1998) ZW10 helps recruit dynactin and dynein to the kinetochore. J Cell Biol 142(3):763–774

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • Stucke VM, Baumann C, Nigg EA (2004) Kinetochore localization and microtubule interaction of the human spindle checkpoint kinase Mps1. Chromosoma 113(1):1–15

    Article  PubMed  CAS  Google Scholar 

  • 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):925–936

    Article  PubMed  CAS  Google Scholar 

  • 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):317–329

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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):387–397

    Article  PubMed  CAS  Google Scholar 

  • 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):1–11

    Article  PubMed  CAS  Google Scholar 

  • 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):4385–4395

    PubMed  CAS  Google Scholar 

  • 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

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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):4584–4596

    Article  PubMed  CAS  Google Scholar 

  • 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):755–766

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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):1181–1191

    Article  PubMed  CAS  Google Scholar 

  • 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):111–123

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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):1127–1140

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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):3133–3143

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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):1245–1254

    PubMed  CAS  Google Scholar 

  • Zirkle RE (1970) Ultraviolet-microbeam irradiation of newt-cell cytoplasm: spindle destruction, false anaphase, and delay of true anaphase. Radiat Res 41(3):516–537

    Article  PubMed  CAS  Google Scholar 

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Acknowledgements

We apologize to the authors whose work was not discussed or cited owing to space limitations. We thank Suzanne Lens, Patrick Meraldi, Michael Lampson and the members of the Kops and Shah laboratories for their insightful comments. Work in the Kops laboratory is supported by the Dutch Cancer Society, by the Netherlands Organization for Scientific Research (NWO), and by the European Research Council (ERC). Work in the Shah laboratory is supported by the US National Institutes of Health (NIH) and the Foundation of the Beckman Laser Institute (BLI).

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Authors and Affiliations

  1. Department of Medical Oncology and Department of Molecular Cancer Research, University Medical Center Utrecht, Utrecht, The Netherlands

    Geert J. P. L. Kops

  2. Department of Systems Biology, Harvard Medical School and Renal Division, Brigham and Women’s Hospital, Boston, MA, USA

    Jagesh V. Shah

  3. Medical Oncology & Molecular Cancer Research, University Medical Center Utrecht, Stratenum 2.231, Universiteitsweg 100, 3584, CG, Utrecht, The Netherlands

    Geert J. P. L. Kops

  4. Department of Systems Biology, Harvard Medical School, 4 Blackfan Circle, HIM 564, Boston, MA, 02115, USA

    Jagesh V. Shah

Authors
  1. Geert J. P. L. Kops
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  2. Jagesh V. Shah
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Corresponding authors

Correspondence to Geert J. P. L. Kops or Jagesh V. Shah.

Additional information

Communicated by Erich Nigg

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Kops, G.J.P.L., Shah, J.V. Connecting up and clearing out: how kinetochore attachment silences the spindle assembly checkpoint. Chromosoma 121, 509–525 (2012). https://doi.org/10.1007/s00412-012-0378-5

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  • DOI: https://doi.org/10.1007/s00412-012-0378-5

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