CoChat
Sign Up
Cited by 4Microtubule and mitosis dynamicsGenomics and Chromatin DynamicsDNA Repair Mechanisms

The DOI matches its Crossref record; 2 of the 2 references it cites were found in a registry or an index.

The Spc105/Kre28 complex promotes mitotic error correction by outer kinetochore recruitment of Ipl1/Sli15

Open access
Dudziak, Alexander, Pleuger, Richard, Schmidt, Jasmin, Hamm, Frederik, Tendulkar, Sharvari, Jänen, Karolin, Vetter, Ingrid R, Singh, Sylvia, Fischböck, Josef, Herzog, Franz, Westermann, Stefan·2025·The EMBO Journal
DOI 10.1038/s44318-025-00437-wPMC PMC12170873

Published version of a preprint

Open this paper in CoChat — free accountOpen PDF

Abstract

Kinetochores link chromosomes to dynamic microtubules of the mitotic spindle. To ensure equal chromosome segregation, sister chromatids must achieve biorientation. The conserved kinase Aurora B phosphorylates outer kinetochore proteins on attachments lacking tension, allowing the re-establishment of new connections until biorientation is achieved. Aurora B localizes to the centromere as part of the chromosomal passenger complex (CPC), but the underlying recruitment pathways can be eliminated without disrupting biorientation. It therefore remains unclear how the kinase operates during error correction. Here, we identify the conserved Spc105/Kre28 complex as an outer kinetochore receptor of the Aurora kinase Ipl1 and its activator Sli15 in Saccharomyces cerevisiae . We show that mutations in the helix bundle domain of Spc105/Kre28 impair mitotic error correction, resembling the effects of ipl1 or sli15 mutants. The defects can be suppressed by the artificial recruitment of Ipl1. In biochemical experiments, Ipl1/Sli15 directly associates with Spc105/Kre28, and a conserved segment in the Sli15 central domain is crucially involved in the binding mechanism. These results have important implications for the mechanism of tension-dependent error correction during chromosome biorientation.

Overview

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1038/s44318-025-00437-w

Cites

2 of 2 references verified0 citation errors · 0 not checkable

Statistics

Verification

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Citations

Cites

Flagged first, then by citations

Research works printed but not linked: 64

  1. Akiyoshi B, Sarangapani KK, Powers AF, Nelson CR, Reichow SL, Arellano-Santoyo H, Gonen T, Ranish JA, Asbury CL, Biggins S (2010) Tension directly stabilizes reconstituted kinetochore-microtubule attachments. Nature 468:576–579 · DOI
  2. Biggins S, Murray AW (2001) The budding yeast protein kinase Ipl1/Aurora allows the absence of tension to activate the spindle checkpoint. Genes Dev 15:3118–3129 · DOI
  3. Broad AJ, DeLuca KF, DeLuca JG (2020) Aurora B kinase is recruited to multiple discrete kinetochore and centromere regions in human cells. J Cell Biol 219:e201905144 · DOI
  4. Caldas GV, DeLuca KF, DeLuca JG (2013) KNL1 facilitates phosphorylation of outer kinetochore proteins by promoting Aurora B kinase activity. J Cell Biol 203:957–969 · DOI
  5. Campbell CS, Desai A (2013) Tension sensing by Aurora B kinase is independent of survivin-based centromere localization. Nature 497:118–121 · DOI
  6. Ciferri C, Pasqualato S, Screpanti E, Varetti G, Santaguida S, Dos Reis G, Maiolica A, Polka J, De Luca JG, De Wulf P et al (2008) Implications for kinetochore-microtubule attachment from the structure of an engineered Ndc80 complex. Cell 133:427–439 · DOI
  7. de Regt AK, Clark CJ, Asbury CL, Biggins S (2022) Tension can directly suppress Aurora B kinase-triggered release of kinetochore-microtubule attachments. Nat Commun 13:2152 · DOI
  8. Dendooven T, Zhang Z, Yang J, McLaughlin SH, Schwab J, Scheres SHW, Yatskevich S, Barford D (2023) Cryo-EM structure of the complete inner kinetochore of the budding yeast point centromere. Sci Adv 9:eadg7480 · DOI · Paper page
  9. Desai A, Rybina S, Müller-Reichert T, Shevchenko A, Shevchenko A, Hyman A, Oegema K (2003) KNL-1 directs assembly of the microtubule-binding interface of the kinetochore in C. elegans. Genes Dev 17:2421–2435 · DOI
  10. 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.e1012 · DOI
  11. Drozdetskiy A, Cole C, Procter J, Barton GJ (2015) JPred4: a protein secondary structure prediction server. Nucleic Acids Res 43:W389–W394 · DOI
  12. Evans R, O’Neill M, Pritzel A, Antropova N, Senior A, Green T, Žídek A, Bates R, Blackwell S, Yim J et al (2022) Protein complex prediction with AlphaFold-Multimer. Preprint at bioRxiv https://doi.org/10.1101/2021.10.04.463034 · DOI · Paper page
  13. Fenech EJ, Cohen N, Kupervaser M, Gazi Z, Schuldiner M (2023) A toolbox for systematic discovery of stable and transient protein interactors in baker’s yeast. Mol Syst Biol 19:e11084 · DOI
  14. Fischbock-Halwachs J, Singh S, Potocnjak M, Hagemann G, Solis-Mezarino V, Woike S, Ghodgaonkar-Steger M, Weissmann F, Gallego LD, Rojas J et al (2019) The COMA complex interacts with Cse4 and positions Sli15/Ipl1 at the budding yeast inner kinetochore. eLife 8:e42879 · DOI
  15. García-Rodríguez LJ, Kasciukovic T, Denninger V, Tanaka TU (2019) Aurora B-INCENP localization at centromeres/inner kinetochores is required for chromosome bi-orientation in budding yeast. Curr Biol 29:1536–1544.e1534 · DOI
  16. Gardner MK, Bouck DC, Paliulis LV, Meehl JB, O’Toole ET, Haase J, Soubry A, Joglekar AP, Winey M, Salmon ED et al (2008) Chromosome congression by Kinesin-5 motor-mediated disassembly of longer kinetochore microtubules. Cell 135:894–906 · DOI
  17. Ghodgaonkar-Steger M, Potocnjak M, Zimniak T, Fischbock-Halwachs J, Solis-Mezarino V, Singh S, Speljko T, Hagemann G, Drexler DJ, Witte G et al (2020) C-terminal motifs of the MTW1 complex cooperatively stabilize outer kinetochore assembly in budding yeast. Cell Rep 32:108190 · DOI
  18. Hadders MA, Hindriksen S, Truong MA, Mhaskar AN, Wopken JP, Vromans MJM, Lens SMA (2020) Untangling the contribution of Haspin and Bub1 to Aurora B function during mitosis. J Cell Biol 219:e201907087 · DOI
  19. Herzog F, Kahraman A, Boehringer D, Mak R, Bracher A, Walzthoeni T, Leitner A, Beck M, Hartl F-U, Ban N et al (2012) Structural probing of a protein phosphatase 2A network by chemical cross-linking and mass spectrometry. Science 337:1348–1352 · DOI
  20. Hindriksen S, Lens SMA, Hadders MA (2017) The ins and outs of aurora B inner centromere localization. Front Cell Dev Biol 5:112 · DOI
  21. Hornung P, Troc P, Malvezzi F, Maier M, Demianova Z, Zimniak T, Litos G, Lampert F, Schleiffer A, Brunner M et al (2014) A cooperative mechanism drives budding yeast kinetochore assembly downstream of CENP-A. J Cell Biol 206:509–524 · DOI
  22. Indjeian VB, Stern BM, Murray AW (2005) The centromeric protein Sgo1 is required to sense lack of tension on mitotic chromosomes. Science 307:130–133 · DOI
  23. Jeyaprakash AA, Klein UR, Lindner D, Ebert J, Nigg EA, Conti E (2007) Structure of a survivin–borealin–INCENP core complex reveals how chromosomal passengers travel together. Cell 131:271–285 · DOI
  24. Kato H, Jiang J, Zhou B-R, Rozendaal M, Feng H, Ghirlando R, Xiao TS, Straight AF, Bai Y (2013) A conserved mechanism for centromeric nucleosome recognition by centromere protein CENP-C. Science 340:1110–1113 · DOI
  25. Katoh K, Rozewicki J, Yamada KD (2019) MAFFT online service: multiple sequence alignment, interactive sequence choice and visualization. Brief Bioinforma 20:1160–1166 · DOI · Paper page
  26. Krenn V, Musacchio A (2015) The aurora B kinase in chromosome bi-orientation and spindle checkpoint signaling. Front Oncol 5:225 · DOI
  27. Krissinel E, Henrick K (2007) Inference of macromolecular assemblies from crystalline state. J Mol Biol 372:774–797 · DOI
  28. Kushnirov VV (2000) Rapid and reliable protein extraction from yeast. Yeast 16:857–860 · DOI
  29. Li S, Garcia-Rodriguez LJ, Tanaka TU (2023) Chromosome biorientation requires Aurora B’s spatial separation from its outer kinetochore substrates, but not its turnover at kinetochores. Curr Biol 33:4557–4569 · DOI
  30. Liu D, Vader G, Vromans MJ, Lampson MA, Lens SM (2009) Sensing chromosome bi-orientation by spatial separation of aurora B kinase from kinetochore substrates. Science 323:1350–1353 · DOI
  31. 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 · DOI
  32. Malvezzi F, Litos G, Schleiffer A, Heuck A, Mechtler K, Clausen T, Westermann S (2013) A structural basis for kinetochore recruitment of the Ndc80 complex via two distinct centromere receptors. EMBO J 32:409–423 · DOI
  33. 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 20:739–750 · DOI
  34. Mirdita M, Schütze K, Moriwaki Y, Heo L, Ovchinnikov S, Steinegger M (2022) ColabFold: making protein folding accessible to all. Nat Methods 19:679–682 · DOI · Paper page
  35. Musacchio A, Desai A (2017) A molecular view of kinetochore assembly and function. Biology 6:5 · DOI
  36. Nijenhuis W, Vallardi G, Teixeira A, Kops GJPL, Saurin AT (2014) Negative feedback at kinetochores underlies a responsive spindle checkpoint signal. Nat Cell Biol 16:1257–1264 · DOI
  37. Pagliuca C, Draviam VM, Marco E, Sorger PK, Wulf PD (2009) Roles for the conserved Spc105p/Kre28p complex in kinetochore-microtubule binding and the spindle assembly checkpoint. PLoS ONE 4:e7640 · DOI
  38. Parnell EJ, Jenson EE, Miller MP (2024) A conserved site on Ndc80 complex facilitates dynamic recruitment of Mps1 to yeast kinetochores to promote accurate chromosome segregation. Curr Biol 34:2294–2307.e2294 · DOI
  39. Perez-Riverol Y, Bai J, Bandla C, Garcia-Seisdedos D, Hewapathirana S, Kamatchinathan S, Kundu DJ, Prakash A, Frericks-Zipper A, Eisenacher M et al (2022) The PRIDE database resources in 2022: a hub for mass spectrometry-based proteomics evidences. Nucleic Acids Res 50:D543–D552 · DOI · Paper page
  40. Pesenti ME, Raisch T, Conti D, Walstein K, 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 82:2113–2131.e2118 · DOI
  41. Petrovic A, Keller J, Liu Y, Overlack K, John J, Dimitrova YN, Jenni S, van Gerwen S, Stege P, Wohlgemuth S et al (2016) Structure of the MIS12 complex and molecular basis of its interaction with CENP-C at human kinetochores. Cell 167:1028–1040.e1015 · DOI
  42. Petrovic A, Mosalaganti S, Keller J, Mattiuzzo M, Overlack K, Krenn V, De Antoni A, Wohlgemuth S, Cecatiello V, Pasqualato S et al (2014) Modular assembly of RWD domains on the mis12 complex underlies outer kinetochore organization. Mol Cell 53:591–605 · DOI
  43. Pettersen EF, Goddard TD, Huang CC, Couch GS, Greenblatt DM, Meng EC, Ferrin TE (2004) UCSF Chimera-a visualization system for exploratory research and analysis. J Comput Chem 25:1605–1612 · DOI
  44. Pleuger R, Cozma C, Hohoff S, Denkhaus C, Dudziak A, Kaschani F, Kaiser M, Musacchio A, Vetter IR, Westermann S (2024) Microtubule end-on attachment maturation regulates Mps1 association with its kinetochore receptor. Curr Biol 34:2279–2293.e2276 · DOI · Paper page
  45. Polley S, Raisch T, Ghetti S, Korner M, Terbeck M, Grater F, Raunser S, Aponte-Santamaria C, Vetter IR, Musacchio A (2024) Structure of the human KMN complex and implications for regulation of its assembly. Nat Struct Mol Biol 31:861–873 · DOI
  46. Rosenberg JS, Cross FR, Funabiki H (2011) KNL1/Spc105 recruits PP1 to silence the spindle assembly checkpoint. Curr Biol 21:942–947 · DOI
  47. Roy B, Sim J, Han SJY, Joglekar AP (2022) Kre28–Spc105 interaction is essential for Spc105 loading at the kinetochore. Open Biol 12:210274
  48. Schmitzberger F, Harrison SC (2012) RWD domain: a recurring module in kinetochore architecture shown by a Ctf19-Mcm21 complex structure. EMBO Rep 13:216–222 · DOI
  49. Sessa F, Mapelli M, Ciferri C, Tarricone C, Areces LB, Schneider TR, Stukenberg PT, Musacchio A (2005) Mechanism of Aurora B Activation by INCENP and Inhibition by Hesperadin. Mol Cell 18:379–391 · DOI
  50. 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 22:891–899 · DOI
  51. Suzuki A, Gupta A, Long SK, Evans R, Badger BL, Salmon ED, Biggins S, Bloom K (2018) A Kinesin-5, Cin8, recruits protein phosphatase 1 to kinetochores and regulates chromosome segregation. Curr Biol 28:2697–2704.e2693 · DOI
  52. Tanaka TU, Zhang T (2022) SWAP, SWITCH, and STABILIZE: mechanisms of kinetochore–microtubule error correction. Cells 11:1462 · DOI
  53. Tromer EC, van Hooff JJE, Kops GJPL, Snel B (2019) Mosaic origin of the eukaryotic kinetochore. Proc Natl Acad Sci USA 116:12873–12882 · DOI
  54. Walzthoeni T, Claassen M, Leitner A, Herzog F, Bohn S, Forster F, Beck M, Aebersold R (2012) False discovery rate estimation for cross-linked peptides identified by mass spectrometry. Nat Methods 9:901–903 · DOI
  55. Wan X, O’Quinn RP, Pierce HL, Joglekar AP, Gall WE, DeLuca JG, Carroll CW, Liu S-T, Yen TJ, McEwen BF et al (2009) Protein architecture of the human kinetochore microtubule attachment site. Cell 137:672–684 · DOI
  56. Waterhouse AM, Procter JB, Martin DMA, Clamp M, Barton GJ (2009) Jalview Version 2—a multiple sequence alignment editor and analysis workbench. Bioinformatics 25:1189–1191 · DOI
  57. Wei RR, Al-Bassam J, Harrison SC (2007) The Ndc80/HEC1 complex is a contact point for kinetochore-microtubule attachment. Nat Struct Mol Biol 14:54–59 · DOI
  58. Weir JR, Faesen AC, Klare K, Petrovic A, Basilico F, Fischböck J, Pentakota S, Keller J, Pesenti ME, Pan D et al (2016) Insights from biochemical reconstitution into the architecture of human kinetochores. Nature 537:249–253 · DOI
  59. Wilson-Kubalek EM, Cheeseman IM, Yoshioka C, Desai A, Milligan RA (2008) Orientation and structure of the Ndc80 complex on the microtubule lattice. J Cell Biol 182:1055–1061 · DOI
  60. Xiao H, Wang F, Wisniewski J, Shaytan AK, Ghirlando R, FitzGerald PC, Huang Y, Wei D, Li S, Landsman D et al (2017) Molecular basis of CENP-C association with the CENP-A nucleosome at yeast centromeres. Genes Dev 31:1958–1972 · DOI
  61. Yamagishi Y, Yang C-H, Tanno Y, Watanabe Y (2012) MPS1/Mph1 phosphorylates the kinetochore protein KNL1/Spc7 to recruit SAC components. Nat Cell Biol 14:746–752 · DOI
  62. Yatskevich S, Muir KW, Bellini D, Zhang Z, Yang J, Tischer T, Predin M, Dendooven T, McLaughlin SH, Barford D (2022) Structure of the human inner kinetochore bound to a centromeric CENP-A nucleosome. Science 376:844–852 · DOI · Paper page
  63. Yatskevich S, Yang J, Bellini D, Zhang Z, Barford D (2024) Structure of the human outer kinetochore KMN network complex. Nat Struct Mol Biol 31:874–883 · DOI · Paper page
  64. Zahm JA, Harrison SC (2024) A communication hub for phosphoregulation of kinetochore-microtubule attachment. Curr Biol 34:2308–2318.e2306 · DOI

Metadata

Authors
Dudziak, A., Pleuger, R., Schmidt, J., Hamm, F., Tendulkar, S., Jänen, K., Vetter, I. R., Singh, S., Fischböck, J., Herzog, F., & Westermann, S.
Affiliations
  • University of Duisburg-Essen (DE)
  • Max Planck Institute of Molecular Physiology (DE)
  • Ludwig-Maximilians-Universität München (DE)
  • IMC University of Applied Sciences Krems (AT)
Corresponding author
Westermann, Stefan
ORCID
Venue
The EMBO Journal
Publisher
Springer Science and Business Media LLC
Published
2025-04-25
Volume
44
Issue
12
Pages
3492-3520
ISSN
  • 0261-4189 (ISSN-L)
  • 1460-2075
DOI
10.1038/s44318-025-00437-w
PMC
PMC12170873
OpenAlex
W4409781585
Cited by
4
References
2
Citations by year
2026: 4
FWCI
2.00
Type
journal article
Language
en
Open access
Licence
Locations
  • The EMBO Journal (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Universitätsbibliographie, Universität Duisburg-Essen (submittedVersion)
  • DuEPublico (University of Duisburg-Essen) (submittedVersion, cc-by)
  • MPG.PuRe (Max Planck Society) (submittedVersion)
Funders
Deutsche Forschungsgemeinschaft (424228829)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Microtubule and mitosis dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
Keywords
Aurora B kinase, outer kinetochore, chromosome biorientation, chromosomal passenger complex, kinetochore-microtubule attachment, protein-protein interaction, Saccharomyces cerevisiae
MeSH terms
Microtubule-Associated Proteins, Mitosis, Mutation, Saccharomyces cerevisiae, Protein Serine-Threonine Kinases, Kinetochores, Cell Cycle Proteins, Chromosome Segregation, Saccharomyces cerevisiae Proteins, Intracellular Signaling Peptides and Proteins, Aurora Kinases

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review