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PreprintCited by 17Microtubule and mitosis dynamicsGenomics and Chromatin DynamicsDNA Repair Mechanisms

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A communication hub for phosphoregulation of kinetochore-microtubule attachment

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Zahm, Jacob A., Harrison, Stephen C.·2023·Current Biology
DOI 10.1101/2023.11.22.568383PMC PMC11847324

Preprint — published as 10.1016/j.cub.2024.04.067

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Abstract

The Mps1 and Aurora B kinases regulate and monitor kinetochore attachment to spindle microtubules during cell division, ultimately ensuring accurate chromosome segregation. In yeast, the critical attachment components are the Ndc80 and Dam1 complexes (Ndc80c and DASH/Dam1c, respectively). Ndc80c is an 600-Å long heterotetramer that binds microtubules through a globular “head” at one end and centromere-proximal kinetochore components through a globular knob at the other end. Dam1c is a heterodecamer that forms a ring of 16-17 protomers around the shaft of the single kinetochore microtubule in point-centromere yeast. The ring coordinates the approximately eight Ndc80c rods per kinetochore. In published work, we showed that a site on the globular “head” of Ndc80c, including residues from both Ndc80 and Nuf2, binds a bipartite segment in the long, C-terminal extension of Dam1. Results reported here show, both by in vitro binding experiments and by crystal structure determination, that the same site binds a conserved segment in the long N-terminal extension of Mps1 and a similarly conserved segment in the N-terminal extension of Ipl1 (yeast Aurora B). Together with results from experiments in yeast cells and from biochemical assays reported in two accompanying papers, the structures and graded affinities identify a communication hub for ensuring uniform bipolar attachment and for signaling anaphase onset.

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Metadata

Authors
Zahm, J. A., & Harrison, S. C.
Affiliations
  • Harvard University (US)
  • Howard Hughes Medical Institute (US)
Corresponding author
Harrison, Stephen C.
ORCID
Venue
Current Biology
Publisher
openRxiv
Published
2023-11-23
Volume
34
Issue
11
Pages
2308-2318.e6
ISSN
0960-9822 (ISSN-L)
DOI
10.1101/2023.11.22.568383
PMC
PMC11847324
OpenAlex
W4398167278
Cited by
17
References
1
Citations by year
2026: 5 · 2025: 6 · 2024: 6
FWCI
3.82
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Current Biology (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion, cc-by)
Funders
  • Howard Hughes Medical Institute
  • American Cancer Society (PF-21-188-01-CCB)
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
kinetochore-microtubule attachment, Mps1 kinase, Aurora B kinase, Ipl1, Ndc80 complex, Dam1 complex, NUF2, spindle assembly checkpoint, chromosome segregation, anaphase onset, protein-protein interaction, crystal structure, Saccharomyces cerevisiae
MeSH terms
Microtubule-Associated Proteins, Microtubules, Nuclear Proteins, Phosphorylation, Saccharomyces cerevisiae, Kinetochores, Cell Cycle Proteins, Saccharomyces cerevisiae Proteins

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