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Cited by 34Microtubule and mitosis dynamicsGenomics and Chromatin DynamicsDNA Repair Mechanisms

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Structural mechanism of outer kinetochore Dam1-Ndc80 complex assembly on microtubules

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Muir, Kyle W., Batters, Christopher, Dendooven, Tom, Yang, Jing, Zhang, Ziguo, Burt, Alister, Barford, David·2023·Science
DOI 10.1126/science.adj8736PMC PMC7615550

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Abstract

Kinetochores couple chromosomes to the mitotic spindle to segregate the genome during cell division. An error correction mechanism drives the turnover of kinetochore-microtubule attachments until biorientation is achieved. The structural basis for how kinetochore-mediated chromosome segregation is accomplished and regulated remains an outstanding question. In this work, we describe the cryo–electron microscopy structure of the budding yeast outer kinetochore Ndc80 and Dam1 ring complexes assembled onto microtubules. Complex assembly occurs through multiple interfaces, and a staple within Dam1 aids ring assembly. Perturbation of key interfaces suppresses yeast viability. Force-rupture assays indicated that this is a consequence of impaired kinetochore-microtubule attachment. The presence of error correction phosphorylation sites at Ndc80-Dam1 ring complex interfaces and the Dam1 staple explains how kinetochore-microtubule attachments are destabilized and reset.

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Metadata

Authors
Muir, K. W., Batters, C., Dendooven, T., Yang, J., Zhang, Z., Burt, A., & Barford, D.
Affiliations
MRC Laboratory of Molecular Biology (GB)
Corresponding author
  • Muir, Kyle W.
  • Barford, David
ORCID
Venue
Science
Publisher
American Association for the Advancement of Science (AAAS)
Published
2023-12-08
Volume
382
Issue
6675
Pages
1184-1190
ISSN
  • 0036-8075 (ISSN-L)
  • 1095-9203
DOI
10.1126/science.adj8736
PMC
PMC7615550
OpenAlex
W4389429528
Cited by
34
References
2
Citations by year
2026: 14 · 2025: 9 · 2024: 9 · 2023: 2
FWCI
4.92
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Science (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion, cc-by)
Funders
  • Wellcome Trust
  • Diamond Light Source (BI31336)
  • UK Research and Innovation (MC_UP_1201/6)
  • Cancer Research UK (24307, C576/A14109, DRCRPG-Jun22\100004, 14109)
  • Medical Research Council (MC_UP_1201/6)
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
outer kinetochore, Dam1 complex, Ndc80 complex, kinetochore-microtubule attachment, chromosome segregation, biorientation, error correction, phosphorylation sites, Saccharomyces cerevisiae, mitotic spindle
MeSH terms
Microtubule-Associated Proteins, Microtubules, Nuclear Proteins, Protein Conformation, Saccharomyces cerevisiae, Kinetochores, Cell Cycle Proteins, Chromosome Segregation, Cryoelectron Microscopy, Saccharomyces cerevisiae Proteins

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