SpringerLink
Log in

On the Regulation of Mitosis by the Kinetochore, a Macromolecular Complex and Organising Hub of Eukaryotic Organisms

  • Chapter
  • First Online:
Macromolecular Protein Complexes IV

Part of the book series: Subcellular Biochemistry ((SCBI,volume 99))

Abstract

The kinetochore is the multiprotein complex of eukaryotic organisms that is assembled on mitotic or meiotic centromeres to connect centromeric DNA with microtubules. Its function involves the coordinated action of more than 100 different proteins. The kinetochore acts as an organiser hub that establishes physical connections with microtubules and centromere-associated proteins and recruits central protein components of the spindle assembly checkpoint (SAC), an evolutionarily conserved surveillance mechanism of eukaryotic organisms that detects unattached kinetochores and destabilises incorrect kinetochore-microtubule attachments. The molecular communication between the kinetochore and the SAC is highly dynamic and tightly regulated to ensure that cells can progress towards anaphase until each chromosome is properly bi-oriented on the mitotic spindle. This is achieved through an interplay of highly cooperative interactions and concerted phosphorylation/dephosphorylation events that are organised in time and space.

This contribution discusses our current understanding of the function, structure and regulation of the kinetochore, in particular, how its communication with the SAC results in the amplification of specific signals to exquisitely control the eukaryotic cell cycle. This contribution also addresses recent advances in machine learning approaches, cell imaging and proteomics techniques that have enhanced our understanding of the molecular mechanisms that ensure the high fidelity and timely segregation of the genetic material every time a cell divides as well as the current challenges in the study of this fascinating molecular machine.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Chapter
USD 29.95
Price excludes VAT (Brazil)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (Brazil)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (Brazil)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free ship** worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (Brazil)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free ship** worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Similar content being viewed by others

References

  • Abrieu A, Magnaghi-Jaulin L, Kahana JA, Peter M, Castro A, Vigneron S, Lorca T, Cleveland DW, Labbe JC (2001) Mps1 is a kinetochore-associated kinase essential for the vertebrate mitotic checkpoint. Cell 106:83–93

    Article  CAS  PubMed  Google Scholar 

  • Allu PK, Dawicki-McKenna JM, Van Eeuwen T, Slavin M, Braitbard M, Xu C, Kalisman N, Murakami K, Black BE (2019) Structure of the human core centromeric nucleosome complex. Curr Biol 29:2625–2639.e5

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Audett MR, Maresca TJ (2020) The whole is greater than the sum of its parts: at the intersection of order, disorder, and kinetochore function. Essays Biochem 64:349–358

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bajaj R, Bollen M, Peti W, Page R (2018) KNL1 binding to PP1 and microtubules is mutually exclusive. Structure 26:1327–1336.e4

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Barbosa J, Conde C, Sunkel C (2020) RZZ-SPINDLY-DYNEIN: you got to keep ʼem separated. Cell Cycle 19:1716–1726

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Blundell TL, Chaplin AK (2021) The resolution revolution in X-ray diffraction, Cryo-EM and other technologies. Prog Biophys Mol Biol 160:2–4

    Article  CAS  PubMed  Google Scholar 

  • Blundell TL, Bolanos-Garcia VM, Chirgadze DY, Harmer NJ, Lo T, Pellegrini L, Sibanda BL (2002) Asymmetry in the multiprotein systems of molecular biology. Struct Chem 13:405–412

    Article  CAS  Google Scholar 

  • Bolanos-Garcia VM, Blundell TL (2011) BUB1 and BUBR1: multifaceted kinases of the cell cycle. Trends Biochem Sci 36:141–150

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bolanos-Garcia VM, Kiyomitsu T, D’Arcy S, Chirgadze DY, Grossmann JG, Matak-Vinkovic D, Venkitaraman AR, Yanagida M, Robinson CV, Blundell TL (2009) The crystal structure of the N-terminal region of BUB1 provides insight into the mechanism of BUB1 recruitment to kinetochores. Structure 17:105–116

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bolanos-Garcia VM, Lischetti T, Matak-Vinkovic 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. Structure 19:1691–1700

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bolanos-Garcia VM, Wu Q, Ochi T, Chirgadze DY, Sibanda BL, Blundell TL (2012) Spatial and temporal organisation of multiprotein assemblies: achieving sensitive control in information-rich cell regulatory systems. Philos Trans A Math Phys Eng Sci 370:3023–3039

    CAS  PubMed  Google Scholar 

  • Boyarchuk Y, Salic A, Dasso M, Arnaoutov A (2007) Bub1 is essential for assembly of the functional inner centromere. J Cell Biol 176:919–928

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Breast Cancer Care (2021). https://www.breastcancercare.org.uk/information-support/facing-breast-cancer/going-through-treatment-breast-cancer/chemotherapy/docetaxel-taxotere

  • Breit C et al (2015) Role of intrinsic and extrinsic factors in the regulation of the mitotic checkpoint kinase Bub1. PLoS One 10:e0144673

    Article  PubMed  PubMed Central  Google Scholar 

  • Broad AJ, DeLuca JG (2020) The right place at the right time: Aurora B kinase localization to centromeres and kinetochores. Essays Biochem 64:299–311

    Article  PubMed  PubMed Central  Google Scholar 

  • Cairo G, Lacefield S (2020) Establishing correct kinetochore-microtubule attachments in mitosis and meiosis. Essays Biochem 64:277–287

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cao B, Zhao C, Zhang Y, Wang X, Ye J, Hu L, He X (2021) The novel interaction mode among centromere sub-complex CENP-O/P/U/Q/R. J Mol Recogn 34:e2892

    Article  CAS  Google Scholar 

  • Carter SL, Eklund AC, Kohane IS, Harris LN, Szallasi Z (2006) A signature of chromosomal instability inferred from gene expression profiles predicts clinical outcome in multiple human cancers. Nat Genet 38:1043–1048

    Article  CAS  PubMed  Google Scholar 

  • Chan GK, Jablonski SA, Sudakin V, Hittle JC, Yen TJ (1999) Human BUBR1 is a mitotic checkpoint kinase that monitors CENP-E functions at kinetochores and binds the cyclosome/APC. J Cell Biol 146:941–954

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chao WC, Kulkarni K, Zhang Z, Kong EH, Barford D (2012) Structure of the mitotic checkpoint complex. Nature 484:208–213

    Article  CAS  PubMed  Google Scholar 

  • Cheeseman IM, Desai A (2008) Molecular architecture of the kinetochore-microtubule interface. Nat Rev Mol Cell Biol 9:33–46

    Article  CAS  PubMed  Google Scholar 

  • Cheeseman IM, Chappie JS, Wilson-Kubalek EM, Desai A (2006) The conserved KMN network constitutes the core microtubule-binding site of the kinetochore. Cell 127:983–997

    Article  CAS  PubMed  Google Scholar 

  • Cheeseman IM, Hori T, Fukagawa T, Desai A (2008) KNL1 and the CENP-H/I/K complex coordinately direct kinetochore assembly in vertebrates. Mol Biol Cell 19:587–594

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chittori S, Hong J, Saunders H, Feng H, Ghirlando R, Kelly AE, Bai Y, Subramaniam S (2018) Structural mechanisms of centromeric nucleosome recognition by the kinetochore protein CENP-N. Science 359:339–343

    Article  CAS  PubMed  Google Scholar 

  • Ciferri C, De Luca J, Monzani S, Ferrari KJ, Ristic D, Wyman C, Stark H, Kilmartin J, Salmon ED, Musacchio A (2005) Architecture of the human Ndc80-Hec1 complex, a critical constituent of the outer kinetochore. J Biol Chem 280:29088–29095

    Article  CAS  PubMed  Google Scholar 

  • Ciferri C, Pasqualato S, Screpanti E, Varetti G, Santaguida S, Dos Reis G, Maiolica A, Polka J, De Luca JG, De Wulf P, Salek M, Rappsilber J, Moores CA, Salmon ED, Musacchio A (2008) Implications for kinetochore-microtubule attachment from the structure of an engineered Ndc80 complex. Cell 133:427–439

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ciossani G, Overlack K, Petrovic A, Huis in ’t Veld PJ, Koerner C, Wohlgemuth S, Maffini S, Musacchio A (2018) The kinetochore proteins CENP-E and CENP-F directly and specifically interact with distinct BUB mitotic checkpoint Ser/Thr kinases. J Biol Chem 293:10084–10101

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Clarke NI, Royle SJ (2018) Correlating light microscopy with serial block face scanning electron microscopy to study mitotic spindle architecture. Methods Cell Biol 145:29–43

    Article  CAS  PubMed  Google Scholar 

  • Cordeiro MH, Smith RJ, Saurin AT (2020) Kinetochore phosphatases suppress autonomous Polo-like kinase 1 activity to control the mitotic checkpoint. J Cell Biol 219:e202002020

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Craske B, Welburn JPI (2020) Leaving no-one behind: how CENP-E facilitates chromosome alignment. Essays Biochem 64:313–324

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Curtis NL, Bolanos-Garcia VM (2019) The anaphase promoting complex/cyclosome (APC/C): a versatile E3 ubiquitin ligase. Subcell Biochem 93:539–623

    Article  PubMed  Google Scholar 

  • Curtis LN, Ruda GF, Brennan P, Bolanos-Garcia VM (2020) Deregulation of chromosome segregation and cancer. Annu Rev Cancer Biol 4:257–278

    Article  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 15:214–225

    Article  PubMed  Google Scholar 

  • DeLuca JG, Musacchio A (2012) Structural organization of the kinetochore-microtubule interface. Curr Opin Cell Biol 24:48–56

    Article  CAS  PubMed  Google Scholar 

  • Dimitrova YN, Jenni S, Valverde R, Khin Y, Harrison SC (2016) Structure of the MIND complex defines a regulatory focus for yeast kinetochore assembly. Cell 167:1014–1027.e12

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Doupé DP, Perrimon N (2016) Toward a systems understanding of signaling pathway function. Curr Top Dev Biol 117:221–236

    Article  PubMed  Google Scholar 

  • Earnshaw WC, Rothfield N (1985) Identification of a family of human centromere proteins using autoimmune sera from patients with scleroderma. Chromosoma 91:313–321

    Article  CAS  PubMed  Google Scholar 

  • Edelmaier C, Lamson AR, Gergely ZR, Ansari S, Blackwell R, McIntosh JR, Glaser MA, Betterton MD (2020) Mechanisms of chromosome biorientation and bipolar spindle assembly analyzed by computational modeling. Elife 9:e48787

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Elowe S (2011) Bub1 and BubR1: at the interface between chromosome attachment and the spindle checkpoint. Mol Cell Biol 31:3085–3093

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Espert A, Uluocak P, Bastos RN, Mangat D, Graab P, Gruneberg U (2014) PP2A-B56 opposes Mps1 phosphorylation of Knl1 and thereby promotes spindle assembly checkpoint silencing. J Cell Biol 206:833–842

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fernius J, Hardwick KG (2007) Bub1 kinase targets Sgo1 to ensure efficient chromosome biorientation in budding yeast mitosis. PLoS Genet 3:e213

    Article  PubMed  PubMed Central  Google Scholar 

  • Ferrand J, Rondinelli B, Polo SE (2020) Histone variants: guardians of genome integrity. Cells 9:2424

    Article  CAS  PubMed Central  Google Scholar 

  • Ferreira LT, Maiato H (2021) Prometaphase. Semin Cell Dev Biol 117:52–61

    Article  CAS  PubMed  Google Scholar 

  • Fischer ES, Yu CWH, Bellini D, McLaughlin SH, Orr CM, Wagner A, Freund SMV, Barford D (2021) Molecular mechanism of Mad1 kinetochore targeting by phosphorylated Bub1. EMBO Rep 22:e52242

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Foley EA, Kapoor TM (2013) Microtubule attachment and spindle assembly checkpoint signalling at the kinetochore. Nat Rev Mol Cell Biol 14:25–37

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Foley EA, Maldonado M, Kapoor TM (2011) Formation of stable attachments between kinetochores and microtubules depends on the B56-PP2A phosphatase. Nat Cell Biol 13:1265–1271

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fuller BG, Stukenberg PT (2009) Cell division: righting the check. Curr Biol 19:R550–R553

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Funabiki H, Wynne DJ (2013) Making an effective switch at the kinetochore by phosphorylation and dephosphorylation. Chromosoma 122:135–158

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gallego-Jara J, Lozano-Terol G, Sola-Martínez RA, Cánovas-Díaz M, de Diego PT (2020) A compressive review about Taxol®: history and future challenges. Molecules 25:5986

    Article  CAS  PubMed Central  Google Scholar 

  • Gama Braga L, Cisneros AF, Mathieu MM, Clerc M, Garcia P, Lottin B, Garand C, Thebault P, Landry CR, Elowe S (2020) BUBR1 pseudokinase domain promotes kinetochore PP2A-B56 recruitment, spindle checkpoint silencing, and chromosome alignment. Cell Rep 33:108397

    Article  CAS  PubMed  Google Scholar 

  • Ghongane P, Kapanidou M, Asghar A, Elowe S, Bolanos-Garcia VM (2014) The dynamic protein KNL1: a kinetochore rendezvous. J Cell Sci 127:3415–3423

    CAS  PubMed  Google Scholar 

  • Gnann C, Cesnik AJ, Lundberg E (2021) Illuminating non-genetic cellular heterogeneity with imaging-based spatial proteomics. Trends Cancer 7:278–282

    Article  CAS  PubMed  Google Scholar 

  • Hamilton GE, Davis TN (2020) Biochemical evidence for diverse strategies in the inner kinetochore. Open Biol 10:200284

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hamilton G, Dimitrova Y, Davis TN (2019) Seeing is believing: our evolving view of kinetochore structure, composition, and assembly. Curr Opin Cell Biol 60:44–52

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hara M, Fukagawa T (2017) Critical foundation of the kinetochore: the constitutive centromere-associated network (CCAN). Prog Mol Subcell Biol 56:29–57

    Article  CAS  PubMed  Google Scholar 

  • Hara M, Fukagawa T (2020) A dynamics of kinetochore structure and its regulations during mitotic progression. Cell Mol Life Sci 77:2981–2995

    Article  CAS  PubMed  Google Scholar 

  • Hara M, Ariyoshi M, Okumura EI, Hori T, Fukagawa T (2018) Multiple phosphorylations control recruitment of the KMN network onto kinetochores. Nat Cell Biol 20:1378–1388

    Article  CAS  PubMed  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 148:871–882

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hayward D, Bancroft J, Mangat D, Alfonso-Pérez T, Dugdale S, McCarthy J, Barr FA, Gruneberg U (2019) Checkpoint signaling and error correction require regulation of the MPS1 T-loop by PP2A-B56. J Cell Biol 218:3188–3199

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hein JB, Garvanska DH, Nasa I, Kettenbach AN, Nilsson J (2021) Coupling of Cdc20 inhibition and activation by BubR1. Cell Biol 220:e202012081

    Article  CAS  Google Scholar 

  • Henen MA, Myers W, Schmitt LR, Wade KJ, Born A, Nichols PJ, Vögeli B (2021) The disordered spindly C-terminus interacts with RZZ subunits ROD-1 and ZWL-1 in the kinetochore through the same sites in C. elegans. J Mol Biol 433:166812

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Henriques AC, Ribeiro D, Pedrosa J, Sarmento B, Silva PMA, Bousbaa H (2019) Mitosis inhibitors in anticancer therapy: When blocking the exit becomes a solution. Cancer Lett 440-441:64–81

    Article  CAS  PubMed  Google Scholar 

  • Hertz EPT, Kruse T, Davey NE, López-Méndez B, Sigurðsson JO, Montoya G, Olsen JV, Nilsson J (2016) A conserved motif provides binding specificity to the PP2A-B56 phosphatase. Mol Cell 63:686–695

    Article  CAS  PubMed  Google Scholar 

  • Hiruma Y, Sacristan C, Pachis ST, Adamopoulos A, Kuijt T, Ubbink M, von Castelmur E, Perrakis A, Kops GJ (2015) Cell division cycle. Competition between MPS1 and microtubules at kinetochores regulates spindle checkpoint signaling. Science 348:1264–1267

    Article  CAS  PubMed  Google Scholar 

  • Hori T, Shang WH, Takeuchi K, Fukagawa T (2013) The CCAN recruits CENP-A to the centromere and forms the structural core for kinetochore assembly. J Cell Biol 200:45–60

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Izawa D, Pines J (2012) Mad2 and the APC/C compete for the same site on Cdc20 to ensure proper chromosome segregation. J Cell Biol 199:27–37

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Janssen A, Kops GJ, Medema RH (2009) Elevating the frequency of chromosome missegregation as a strategy to kill tumor cells. Proc Natl Acad Sci USA 106:19108–19113

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ji Z, Gao H, Yu H (2015) Cell division cycle. Kinetochore attachment sensed by competitive Mps1 and microtubule binding to Ndc80C. Science 348:1260–1264

    Article  CAS  PubMed  Google Scholar 

  • Ji Z, Gao H, Jia L, Li B, Yu H (2017) A sequential multi-target Mps1 phosphorylation cascade promotes spindle checkpoint signaling. Elife 6:e22513

    Article  PubMed  PubMed Central  Google Scholar 

  • Jia L, Kim S, Yu H (2013) Tracking spindle checkpoint signals from kinetochores to APC/C. Trends Biochem Sci 38:302–311

    Article  CAS  PubMed  Google Scholar 

  • Joglekar AP, DeLuca JG (2009) Chromosome segregation: Ndc80 can carry the load. Curr Biol 19:R404–R407

    Article  CAS  PubMed  Google Scholar 

  • Jones S, Thornton JM (1996) Principles of protein-protein interactions. Proc Natl Acad Sci USA 93:13–20

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jumper J, Evans R, Pritzel A, Green T, Figurnov M, Ronneberger O, Tunyasuvunakool K, Bates R, Žídek A, Potapenko A, Bridgland A, Meyer C, Kohl SAA, Ballard AJ, Cowie A, Romera-Paredes B, Nikolov S, Jain R, Adler J, Back T, Petersen S, Reiman D, Clancy E, Zielinski M, Steinegger M, Pacholska M, Berghammer T, Bodenstein S, Silver D, Vinyals O, Senior AW, Kavukcuoglu K, Kohli P, Hassabis D (2021) Highly accurate protein structure prediction with AlphaFold. Nature 596:583–589

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kim SC, Sprung R, Chen Y, Xu Y, Ball H, Pei J, Cheng T, Kho Y, **ao H, **ao L, Grishin NV, White M, Yang XJ, Zhao Y (2006) Substrate and functional diversity of lysine acetylation revealed by a proteomics survey. Mol Cell 23:607–618

    Article  CAS  PubMed  Google Scholar 

  • Kixmoeller K, Allu PK, Black BE (2020) The centromere comes into focus: from CENP-A nucleosomes to kinetochore connections with the spindle. Open Biol 10:200051

    Article  CAS  PubMed  PubMed Central  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 13:663–676

    Article  CAS  PubMed  Google Scholar 

  • Kiyomitsu T, Murakami H, Yanagida M (2011) Protein interaction domain map** of human kinetochore protein Blinkin reveals a consensus motif for binding of spindle assembly checkpoint proteins Bub1 and BubR1. Mol Cell Biol 31:998–1011

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Klemm C, Thorpe PH, Ólafsson G (2021) Cell-cycle phospho-regulation of the kinetochore. Curr Genet 67:177–193

    Article  CAS  PubMed  Google Scholar 

  • Knossow M, Campanacci V, Khodja LA, Gigant B (2020) The mechanism of tubulin assembly into microtubules: insights from structural studies. iScience 23:101511

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Komaki S, Schnittger A (2016) The spindle checkpoint in plants-a green variation over a conserved theme? Curr Opin Plant Biol 34:84–91

    Article  CAS  PubMed  Google Scholar 

  • Komaki S, Schnittger A (2017) The spindle assembly checkpoint in Arabidopsis is rapidly shut off during severe stress. Dev Cell 43:172–185.e5

    Article  CAS  PubMed  Google Scholar 

  • Kops GJ, Kim Y, Weaver BA, Mao Y, McLeod I, Yates JR 3rd, Tagaya M, Cleveland DW (2005) ZW10 links mitotic checkpoint signaling to the structural kinetochore. J Cell Biol 169:49–60

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kops GJPL, Snel B, Tromer EC (2020) Evolutionary dynamics of the spindle assembly checkpoint in eukaryotes. Curr Biol 30:R589–R602

    Article  CAS  PubMed  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. J Cell Biol 196:451–467

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lander GC, Glaeser RM (2021) Conquer by cryo-EM without physically dividing. Biochem Soc Trans. 49:2287–2298

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lara-Gonzalez P, Westhorpe FG, Taylor SS (2012) The spindle assembly checkpoint. Curr Biol 22:R966–R980

    Article  CAS  PubMed  Google Scholar 

  • Lara-Gonzalez P, Pines J, Desai A (2021) Spindle assembly checkpoint activation and silencing at kinetochores. Semin Cell Dev Biol 117:86–98

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lara-Gonzalez P, Kim T, Oegema K, Corbett K, Desai A (2021b) A tripartite mechanism catalyzes Mad2-Cdc20 assembly at unattached kinetochores. Science 371:64–67

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Larsen NA, Harrison SC (2004) Crystal structure of the spindle assembly checkpoint protein Bub3. J Mol Biol 344:885–892

    Article  CAS  PubMed  Google Scholar 

  • Lawrimore J, Doshi A, Walker B, Bloom K (2019) AI-assisted forward modeling of biological structures. Front Cell Dev Biol 7:279

    Article  PubMed  PubMed Central  Google Scholar 

  • Legal T, Hayward D, Gluszek-Kustusz A, Blackburn EA, Spanos C, Rappsilber J, Gruneberg U, Welburn JPI (2020) The C-terminal helix of BubR1 is essential for CENP-E-dependent chromosome alignment. J Cell Sci 133:jcs246025

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lermontova I, Fuchs J, Schubert I (2008) The Arabidopsis checkpoint protein Bub3.1 is essential for gametophyte development. Front Biosci 13:5202–5211

    Article  CAS  PubMed  Google Scholar 

  • Liotta LA, Pappalardo PA, Carpino A, Haymond A, Howard M, Espina V, Wulfkuhle J, Petricoin E (2021) Laser capture proteomics: spatial tissue molecular profiling from the bench to personalized medicine. Expert Rev Proteomics 18:845–861

    Article  CAS  PubMed  Google Scholar 

  • Liu D, Vleugel M, Backer CB, Hori T, Fukagawa T, Cheeseman IM, Lampson LA (2010) Regulated targeting of protein phosphatase 1 to the outer kinetochore by KNL1 opposes Aurora B kinase. J Cell Biol 188:809–920

    Article  CAS  PubMed  PubMed Central  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 22:900–906

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Long AF, Suresh P, Dumont S (2020) Individual kinetochore-fibers locally dissipate force to maintain robust mammalian spindle structure. J Cell Biol 219:e201911090

    Article  PubMed  PubMed Central  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 9:59–71

    Article  PubMed  Google Scholar 

  • Luo X, Tang Z, **a G, Wassmann K, Matsumoto T, Rizo J, Yu H (2004) The Mad2 spindle checkpoint protein has two distinct natively folded states. Nat Struct Mol Biol 11:338–345

    Article  CAS  PubMed  Google Scholar 

  • Lyseng-Williamson KA, Fenton C (2005) Docetaxel: a review of its use in metastatic breast cancer. Drugs 65:2513–2531

    Article  CAS  PubMed  Google Scholar 

  • Maciejowski J, George KA, Terret ME, Zhang C, Shokat KM, Jallepalli PV (2010) Mps1 directs the assembly of Cdc20 inhibitory complexes during interphase and mitosis to control M phase timing and spindle checkpoint signaling. J Cell Biol 190:89–100

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mao YS, Zhang B, Spector DL (2011) Biogenesis and function of nuclear bodies. Trends Genet 27:295–306

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Matesanz R, Barasoain I, Yang CG, Wang L, Li X, de Inés C, Coderch C, Gago F, Barbero JJ, Andreu JM, Fang WS, Díaz JF (2008) Optimization of taxane binding to microtubules: binding affinity dissection and incremental construction of a high-affinity analog of paclitaxel. Chem Biol 15:573–585

    Article  CAS  PubMed  Google Scholar 

  • Matson DR, Stukenberg PT (2011) Spindle poisons and cell fate: a tale of two pathways. Mol Interven 11:141–150

    Article  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 17:101–114

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • McCleland ML, Kallio MJ, Barrett-Wilt GA, Kestner CA, Shabanowitz J, Hunt DF, Gorbsky GJ, Stukenberg PT (2004) The vertebrate Ndc80 complex contains Spc24 and Spc25 homologs, which are required to establish and maintain kinetochore-microtubule attachment. Curr Biol 14:131–137

    Article  CAS  PubMed  Google Scholar 

  • McKinley KL, Cheeseman IM (2016) The molecular basis for centromere identity and function. Nat Rev Mol Cell Biol 17:16–29

    Article  CAS  PubMed  Google Scholar 

  • McVey SL, Cosby JK, Nannas NJ (2021) Aurora B tension sensing mechanisms in the kinetochore ensure accurate chromosome segregation. Int J Mol Sci 22:8818

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Morrow CJ, Tighe A, Johnson VL, Scott MI, Ditchfield C, Taylor SS (2005) BUB1 and aurora B cooperate to maintain BubR1-mediated inhibition of APC/CCDC20. J Cell Sci 118:3639–3652

    Article  CAS  PubMed  Google Scholar 

  • Mosalaganti S, Keller J, Altenfeld A, Winzker M, Rombaut P, Saur M, Petrovic A, Wehenkel A, Wohlgemuth S, Müller F, Maffini S, Bange T, Herzog F, Waldmann H, Raunser S, Musacchio A (2017) Structure of the RZZ complex and molecular basis of its interaction with Spindly. J Cell Biol 216:961–981

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Moura M, Conde C (2019) Phosphatases in mitosis: roles and regulation. Biomolecules 9:55

    Article  PubMed Central  Google Scholar 

  • Musacchio A, Desai A (2017) A molecular view of kinetochore assembly and function. Biology 6:5

    Article  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  • Navarro AP, Cheeseman IM (2021) Kinetochore assembly throughout the cell cycle. Semin Cell Dev Biol 117:62–74

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nijenhuis W, Vallardi G, Teixeira A, Kops GJ, Saurin AT (2014) Negative feedback at kinetochores underlies a responsive spindle checkpoint signal. Nat Cell Biol 16:1257–1264

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Novais P, Silva PMA, Moreira J, Palmeira A, Amorim I, Pinto M, Cidade H, Bousbaa H (2021) BP-M345, a new diarylpentanoid with promising antimitotic activity. Molecules 26:7139

    Article  CAS  PubMed  PubMed Central  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 Biol 6:1135–1141

    Article  CAS  PubMed  Google Scholar 

  • Palmer DK, O’Day K, Wener MH, Andrews BS, Margolis RL (1987) A 17-kD centromere protein (CENP-A) copurifies with nucleosome core particles and with histones. J Cell Biol 104:805–815

    Article  CAS  PubMed  Google Scholar 

  • Pawson T, Nash P (2003) Assembly of cell regulatory systems through protein interaction domains. Science 300:445–452

    Article  CAS  PubMed  Google Scholar 

  • Pentakota S, Zhou K, Smith C, Maffini S, Petrovic A, Morgan GP, Weir JR, Vetter IR, Musacchio A, Luger K (2017) Decoding the centromeric nucleosome through CENP-N. Elife 6:e33442

    Article  PubMed  PubMed Central  Google Scholar 

  • Peplowska K, Wallek AU, Storchova Z (2014) Sgo1 regulates both condensin and Ipl1/Aurora B to promote chromosome biorientation. PLoS Genet 10:e1004411

    Article  PubMed  PubMed Central  Google Scholar 

  • Pereira C, Reis RM, Gama JB, Celestino R, Cheerambathur DK, Carvalho AX, Gassmann R (2018) Self-assembly of the RZZ complex into filaments drives kinetochore expansion in the absence of microtubule attachment. Curr Biol 28:3408–3421.e8

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Perpelescu M, Fukagawa T (2011) The ABCs of CENPs. Chromosoma 120:425–446

    Article  PubMed  Google Scholar 

  • Pesenti ME, Raisch T, Conti D, Hoffmann I, Vogt D, Prumbaum D, Vetter IR, Raunser S, Musacchio A (2022) Structure of the human inner kinetochore CCAN complex and its significance for human centromere organization. Mol Cell S1097-2765:00390-2.

    Google Scholar 

  • Petrov PN, Müller H, Glaeser RM (2021) Perspective: emerging strategies for determining atomic-resolution structures of macromolecular complexes within cells. J Struct Biol 214:107827

    Article  PubMed  PubMed Central  Google Scholar 

  • Petrovic A, Pasqualato S, Dube P, Krenn V, Santaguida S, Cittaro D, Monzani S, Massimiliano L, Keller J, Tarricone A, Maiolica A, Stark H, Musacchio A (2010) The MIS12 complex is a protein interaction hub for outer kinetochore assembly. J Cell Biol 190:835–852

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Petrovic A, Mosalaganti S, Keller J, Mattiuzzo M, Overlack K, Krenn V, De Antoni A, Wohlgemuth S, Cecatiello V, Pasqualato S, Raunser S, Musacchio A (2014) Modular assembly of RWD domains on the Mis12 complex underlies outer kinetochore organization. Mol Cell 53:591–605

    Article  CAS  PubMed  Google Scholar 

  • Petrovic A, Keller J, Liu Y, Overlack K, John J, Dimitrova YN, Jenni S, van Gerwen S, Stege P, Wohlgemuth S, Rombaut P, Herzog F, Harrison SC, Vetter IR, Musacchio A (2016) Structure of the MIS12 Complex and molecular basis of its interaction with CENP-C at human kinetochores. Cell 167:1028–1040.e15

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Piano V, Alex A, Stege P, Maffini S, Stoppiello GA, Huis In 't Veld PJ, Vetter IR, Musacchio A (2021) CDC20 assists its catalytic incorporation in the mitotic checkpoint complex. Science 371:67–71

    Article  CAS  PubMed  Google Scholar 

  • Ponjavić I, VukuÅ¡ić K, Tolić IM (2021) Expansion microscopy of the mitotic spindle. Methods Cell Biol 161:247–274

    Article  PubMed  Google Scholar 

  • Primorac I, Weir JR, Chiroli E, Gross F, Hoffmann I, van Gerwen S, Ciliberto A, Musacchio A (2013) Bub3 reads phosphorylated MELT repeats to promote spindle assembly checkpoint signaling. Elife 2:e01030

    Article  PubMed  PubMed Central  Google Scholar 

  • Przewloka MR, Glover DM (2009) The kinetochore and the centromere: a working long distance relationship. Annu Rev Genet 43:439–465

    Article  CAS  PubMed  Google Scholar 

  • Przewloka MR, Venkei Z, Bolanos-Garcia VM, Debski J, Dadlez M, Glover DM (2011) CENP-C is a structural platform for kinetochore assembly. Curr Biol 21:399–405

    Article  CAS  PubMed  Google Scholar 

  • Qian J, García-Gimeno MA, Beullens M, Manzione MG, Van der Hoeven G, Igual JC, Heredia M, Sanz P, Gelens L, Bollen M (2017) An attachment-independent biochemical timer of the spindle assembly checkpoint. Mol Cell 68:715–730.e5

    Article  CAS  PubMed  Google Scholar 

  • Rago F, Gascoigne KE, Cheeseman IM (2015) Distinct organization and regulation of the outer kinetochore KMN network downstream of CENP-C and CENP-T. Curr Biol 25:671–677

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ren X, Zhao B, Chang H, **ao M, Wu Y, Liu Y (2018) Paclitaxel suppresses proliferation and induces apoptosis through regulation of ROS and the AKT/MAPK signaling pathway in canine mammary gland tumor cells. Mol Med Rep 17:8289–8299

    CAS  PubMed  PubMed Central  Google Scholar 

  • Renda F, Khodjakov A (2021) Role of spatial patterns and kinetochore architecture in spindle morphogenesis. Semin Cell Dev Biol 117:75–85

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rodriguez-Rodriguez JA, Lewis C, McKinley KL, Sikirzhytski V, Corona J, Maciejowski J, Khodjakov A, Cheeseman IM, Jallepalli PV (2018) Distinct roles of RZZ and Bub1-KNL1 in mitotic checkpoint signaling and kinetochore expansion. Curr Biol 28:3422–3429.e5

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rosenberg JS, Cross FR, Funabiki H (2011) KNL1/Spc105 recruits PP1 to silence the spindle assembly checkpoint. Curr Biol 21:942–947

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sacristan C, Ahmad MUD, Keller J, Fermie J, Groenewold V, Tromer E, Fish A, Melero R, Carazo JM, Klumperman J, Musacchio A, Perrakis A, Kops GJ (2018) Dynamic kinetochore size regulation promotes microtubule capture and chromosome biorientation in mitosis. Nat Cell Biol 20:800–810

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Santaguida S, Musacchio A (2009) The life and miracles of kinetochores. EMBO J 28:2511–2531

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sarangapani KK, Koch LB, Nelson CR, Asbury CL, Biggins S (2021) Kinetochore-bound Mps1 regulates kinetochore-microtubule attachments via Ndc80 phosphorylation. J Cell Biol 220:e202106130

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sarkar S, Sahoo PK, Mahata S, Pal R, Ghosh D, Mistry T, Ghosh S, Bera T, Nasare VD (2021) Mitotic checkpoint defects: en route to cancer and drug resistance. Chromosome Res 29:131–144

    Article  CAS  PubMed  Google Scholar 

  • Scarborough EA, Davis TN, Asbury CL (2019) Tight bending of the Ndc80 complex provides intrinsic regulation of its binding to microtubules. Elife 8:e44489

    Article  PubMed  PubMed Central  Google Scholar 

  • Screpanti E, De Antoni A, Alushin GM, Petrovic A, Melis T, Nogales E, Musacchio A (2011) Direct binding of Cenp-C to the Mis12 complex joins the inner and outer kinetochore. Curr Biol 20:391–398

    Article  Google Scholar 

  • Seet BT, Dikic I, Zhou MM, Pawson T (2006) Reading protein modifications with interaction domains. Nat Rev Mol Cell Biol 7:473–483

    Article  CAS  PubMed  Google Scholar 

  • Shepperd LA, Meadows JC, Sochaj AM, Lancaster TC, Zou J, Buttrick GJ, Rappsilber J, Hardwick KG, Millar JB (2012) Phosphodependent recruitment of Bub1 and Bub3 to Spc7/KNL1 by Mph1 kinase maintains the spindle checkpoint. Curr Biol 22:891–899

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shrestha RL, Conti D, Tamura N, Braun D, Ramalingam RA, Cieslinski K, Ries J, Draviam VM (2017) Aurora-B kinase pathway controls the lateral to end-on conversion of kinetochore-microtubule attachments in human cells. Nat Commun 8:150

    Article  PubMed  PubMed Central  Google Scholar 

  • Simorellis AK, Flynn PF (2006) Fast local backbone dynamics of encapsulated ubiquitin. J Am Chem Soc 128:9580–9581

    Article  CAS  PubMed  Google Scholar 

  • Sironi L, Mapelli M, Knapp S, De Antoni A, Jeang KT, Musacchio A (2002) Crystal structure of the tetrameric Mad1-Mad2 core complex: implications of a ‘safety belt’ binding mechanism for the spindle checkpoint. EMBO J 21:2496–2506

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Starr DA, Saffery R, Li Z, Simpson AE, Choo KH, Yen TJ, Goldberg ML (2000) HZwint-1, a novel human kinetochore component that interacts with HZW10. J Cell Sci 113:1939–1950

    Article  CAS  PubMed  Google Scholar 

  • Strobel T, Swanson L, Korsmeyer S, Cannistra SA (1996) BAX enhances paclitaxel-induced apoptosis through a P53-independent pathway. Proc Natl Acad Sci USA 93:14094–14099

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Su H, Liu Y, Wang C, Liu Y, Feng C, Sun Y, Yuan J, Birchler JA, Han F (2021) Knl1 participates in spindle assembly checkpoint signaling in maize. Proc Natl Acad Sci USA 118:e2022357118

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Suijkerbuijk SJ, van Dam TJ, Karagöz GE, von Castelmur E, Hubner NC, Duarte AM, Vleugel M, Perrakis A, Rüdiger SG, Snel B, Kops GJ (2012) The vertebrate mitotic checkpoint protein BUBR1 is an unusual pseudokinase. Dev Cell 22:1321–1329

    Article  CAS  PubMed  Google Scholar 

  • Tanaka K (2013) Regulatory mechanisms of kinetochore-microtubule interaction in mitosis. Cell Mol Life Sci 70:559–579

    Article  CAS  PubMed  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 16:387–397

    Article  CAS  PubMed  Google Scholar 

  • Tian T, Li X, Liu Y, Wang C, Liu X, Bi G, Zhang X, Yao X, Zhou ZH, Zang J (2018) Molecular basis for CENP-N recognition of CENP-A nucleosome on the human kinetochore. Cell Res 28:374–378

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tipton AR, Ji W, Sturt-Gillespie B, Bekier ME 2nd, Wang K, Taylor WR, Liu ST (2013) Monopolar spindle 1 (MPS1) kinase promotes production of closed MAD2 (C-MAD2) conformer and assembly of the mitotic checkpoint complex. J Biol Chem 288:35149–35158

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Trinkle-Mulcahy L (2019) Recent advances in proximity-based labeling methods for interactome map**. F1000Res 8:F1000

    Article  PubMed  PubMed Central  Google Scholar 

  • Tromer E, Snel B, Kops GJPL (2015) Widespread recurrent patterns of rapid repeat evolution in the kinetochore scaffold KNL1. Genome Biol Evol 7:2383–2393

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tromer E, Bade D, Snel B, Kops GJ (2016) Phylogenomics guided discovery of a novel conserved cassette of short linear motifs in BubR1 essential for the spindle checkpoint. Open Biol 6:160315

    Article  PubMed  PubMed Central  Google Scholar 

  • Tromer EC, van Hooff JJE, Kops GJPL, Snel B (2019) Mosaic origin of the eukaryotic kinetochore. Proc Natl Acad Sci USA 116:12873–12882

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ustinov NB, Korshunova AV, Gudimchuk NB (2020) Protein complex NDC80: properties, functions, and possible role in pathophysiology of cell division. Biochemistry (Mosc) 85:448–462

    Article  CAS  Google Scholar 

  • Vallardi G, Allan LA, Crozier L, Saurin AT (2019) Division of labour between PP2A-B56 isoforms at the centromere and kinetochore. Elife 8:e42619

    Article  PubMed  PubMed Central  Google Scholar 

  • van Hooff JJ, Tromer E, van Wijk LM, Snel B, Kops GJ (2017) Evolutionary dynamics of the kinetochore network in eukaryotes as revealed by comparative genomics. EMBO Rep 18:1559–1571

    Article  PubMed  PubMed Central  Google Scholar 

  • Vanoosthuyse V, Hardwick KG (2005) Bub1 and the multilayered inhibition of CDC20-APC/C in mitosis. Trends Cell Biol 15:231–233

    Article  CAS  PubMed  Google Scholar 

  • Varadi M, Anyango S, Deshpande M, Nair S, Natassia C, Yordanova G, Yuan D, Stroe O, Wood G, Laydon A, Žídek A, Green T, Tunyasuvunakool K, Petersen S, Jumper J, Clancy E, Green R, Vora A, Lutfi M, Figurnov M, Cowie A, Hobbs N, Kohli P, Kleywegt G, Birney E, Hassabis D, Velankar S (2022) AlphaFold protein structure database: massively expanding the structural coverage of protein-sequence space with high-accuracy models. Nucleic Acids Res 50:D439–D444

    Article  CAS  PubMed  Google Scholar 

  • Varma D, Salmon ED (2012) The KMN protein network – chief conductors of the kinetochore orchestra. J Cell Sci 125:5927–5936

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Varma D, Wan X, Cheerambathur D, Gassmann R, Suzuki A, Lawrimore J, Desai A, Salmon ED (2013) Spindle assembly checkpoint proteins are positioned close to core microtubule attachment sites at kinetochores. J Cell Biol 202:735–746

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Venkei Z, Przewloka MR, Glover DM (2011) Drosophila Mis12 complex acts as a single functional unit essential for anaphase chromosome movement and a robust spindle assembly checkpoint. Genetics 187:131–140

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Vetter IR, Pesenti M, Raisch T. (2021) Structure of the human inner kinetochore CCAN complex. Protein Data Bank ID 7QOO

    Google Scholar 

  • Vleugel M, Tromer E, Omerzu M, Groenewold V, Nijenhuis W, Snel B, Kops GJ (2013) Arrayed BUB recruitment modules in the kinetochore scaffold KNL1 promote accurate chromosome segregation. J Cell Biol 203:943–955

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • von Schubert C, Cubizolles F, Bracher JM, Sliedrecht T, Kops GJPL, Nigg EA (2015) Plk1 and Mps1 cooperatively regulate the spindle assembly checkpoint in human cells. Cell Rep 12:66–78

    Article  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 137:672–684

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wan J, Subramonian D, Zhang XD (2012) SUMOylation in control of accurate chromosome segregation during mitosis. Curr Protein Pept Sci 13:467–481

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wang H, Hu X, Ding X, Dou Z, Yang Z, Shaw AW, Teng M, Cleveland DW, Goldberg ML, Niu L, Yao X (2004) Human Zwint-1 specifies localization of Zeste White 10 to kinetochores and is essential for mitotic checkpoint signaling. J Biol Chem 279:54590–54598

    Article  CAS  PubMed  Google Scholar 

  • Wang X, Bajaj R, Bollen M, Peti W, Page R (2016a) Expanding the PP2A interactome by defining a B56-specific SLiM. Structure 24:2174–2181

    Article  PubMed  PubMed Central  Google Scholar 

  • Wang J, Wang Z, Yu T, Yang H, Virshup DM, Kops GJ, Lee SH, Zhou W, Li X, Xu W, Rao Z (2016b) Crystal structure of a PP2A B56-BubR1 complex and its implications for PP2A substrate recruitment and localization. Protein Cell 7:516–526

    Article  CAS  PubMed  PubMed Central  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 13:3029–3041

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Watanabe R, Hara M, Okumura EI, Hervé S, Fachinetti D, Ariyoshi M, Fukagawa T (2019) CDK1-mediated CENP-C phosphorylation modulates CENP-A binding and mitotic kinetochore localization. J Cell Biol 218:4042–4062

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wei RR, Sorger PK, Harrison SC (2005) Molecular organization of the Ndc80 complex, an essential kinetochore component. Proc Natl Acad Sci USA 102:5363–5367

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wei RR, Al-Bassam J, Harrison SC (2007) The Ndc80/HEC1 complex is a contact point for kinetochore-microtubule attachment. Nat Struct Mol Biol 14:54–55

    Article  CAS  PubMed  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 132:111–123

    Article  CAS  PubMed  Google Scholar 

  • Welburn JP, Vleugel M, Liu D, Yates JR 3rd, Lampson MA, Fukagawa T, Cheeseman IM (2010) Aurora B phosphorylates spatially distinct targets to differentially regulate the kinetochore-microtubule interface. Mol Cell 38:383–392

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Westhorpe FG, Straight AF (2013) Functions of the centromere and kinetochore in chromosome segregation. Curr Opin Cell Biol 25:334–340

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wigge PA, Kilmartin JV (2001) The Ndc80p complex from Saccharomyces cerevisiae contains conserved centromere components and has a function in chromosome segregation. J Cell Biol 152:349–360

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wimbish RT, DeLuca JG (2020) Hec1/Ndc80 tail domain function at the kinetochore-microtubule interface. Front Cell Dev Biol 8:43

    Article  PubMed  PubMed Central  Google Scholar 

  • **ng QR, Cipta NO, Hamashima K, Liou YC, Koh CG, Loh YH (2020) Unraveling heterogeneity in transcriptome and its regulation through single-cell multi-omics technologies. Front Genet 11:662

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Xu P, Raetz EA, Kitagawa M, Virshup DM, Lee SH (2013) BUBR1 recruits PP2A via the B56 family of targeting subunits to promote chromosome congression. Biol Open 2:479–486

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yamagishi Y, Yang CH, Tanno Y, Watanabe Y (2012) MPS1/Mph1 phosphorylates the kinetochore protein KNL1/Spc7 to recruit SAC components. Nat Cell Biol 14:746–752

    Article  CAS  PubMed  Google Scholar 

  • Yamamoto A (2021) Shake it off: the elimination of erroneous kinetochore-microtubule attachments and chromosome oscillation. Int J Mol Sci 22:3174

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yan K, Yang J, Zhang Z, McLaughlin SH, Chang L, Fasci D, Ehrenhofer-Murray AE, Heck AJR, Barford D (2019) Structure of the inner kinetochore CCAN complex assembled onto a centromeric nucleosome. Nature 574:278–282

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yao Y, Dai W (2012) Mitotic checkpoint control and chromatin remodeling. Front Biosci 17:976–983

    Article  CAS  Google Scholar 

  • Zhang G, Lischetti T, Nilsson J (2014) A minimal number of MELT repeats supports all functions of KNL1 in chromosome segregation. J Cell Sci 127:871–884

    CAS  PubMed  Google Scholar 

  • Zhang G, Kruse T, López-Méndez B, Sylvestersen KB, Garvanska DH, Schopper S, Nielsen ML, Nilsson J (2017) Bub1 positions Mad1 close to KNL1 MELT repeats to promote checkpoint signalling. Nat Commun 8:15822

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhang G, Kruse T, Guasch Boldú C, Garvanska DH, Coscia F, Mann M, Barisic M, Nilsson J (2019) Efficient mitotic checkpoint signaling depends on integrated activities of Bub1 and the RZZ complex. EMBO J 38:e100977

    Article  PubMed  PubMed Central  Google Scholar 

  • Zhu T, Dou Z, Qin B, ** C, Wang X, Xu L, Wang Z, Zhu L, Liu F, Gao X, Ke Y, Wang Z, Aikhionbare F, Fu C, Ding X, Yao X (2013) Phosphorylation of microtubule-binding protein Hec1 by mitotic kinase Aurora B specifies spindle checkpoint kinase Mps1 signaling at the kinetochore. J Biol Chem 288:36149–36159

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgments

I thank Andrea Musacchio, Stefan Raunser and Ingrid Vetter of the Max-Planck Institute of Molecular Physiology, Dortmund, Germany, for kindly sharing the atom coordinates of the human CCAN complex (PDB ID 7QOO) prior to its publication.

Author information

Authors and Affiliations

  1. Department of Biological and Medical Sciences, Faculty of Health and Life Sciences, Oxford Brookes University, Oxford, UK

    Victor M. Bolanos-Garcia

Authors
  1. Victor M. Bolanos-Garcia
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Victor M. Bolanos-Garcia .

Editor information

Editors and Affiliations

  1. Institute of Molecular Physiology, University of Mainz, Mainz, Germany

    J. Robin Harris

  2. Biosciences Institute, Newcastle University, Newcastle upon Tyne, UK

    Jon Marles-Wright

Rights and permissions

Reprints and permissions

Copyright information

© 2022 The Author(s), under exclusive license to Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Bolanos-Garcia, V.M. (2022). On the Regulation of Mitosis by the Kinetochore, a Macromolecular Complex and Organising Hub of Eukaryotic Organisms. In: Harris, J.R., Marles-Wright, J. (eds) Macromolecular Protein Complexes IV. Subcellular Biochemistry, vol 99. Springer, Cham. https://doi.org/10.1007/978-3-031-00793-4_7

Download citation

Publish with us

Policies and ethics

Search

Navigation