Evidence map›Paper›PMID 41099706›Full record

ArticleNucleic acids research2025

Direct observation of interdependent and hierarchical kinetochore assembly on individual centromeres.

Changkun Hu, Andrew R Popchock, Angelica Andrade Latino, Charles L Asbury, Sue Biggins

Abstract read
In one paragraph

Article in Nucleic acids research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

7 citing papers in PubMed.

  1. Structure and function of the centromere and inner kinetochore.Nature reviews. Molecular cell biology · 2026
    Review
  2. An interdependent Cbf1-CCAN interaction stabilizes the budding yeast kinetochore.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

5 authors.

Changkun HuBasic Sciences Division, Howard Hughes Medical Institute, Fred Hutchinson Cancer Center, Seattle, WA 98109, United States.
Andrew R PopchockBasic Sciences Division, Howard Hughes Medical Institute, Fred Hutchinson Cancer Center, Seattle, WA 98109, United States.
Angelica Andrade LatinoBasic Sciences Division, Howard Hughes Medical Institute, Fred Hutchinson Cancer Center, Seattle, WA 98109, United States.
Charles L AsburyDepartment of Neurobiology and Biophysics, University of Washington, Seattle, WA 98195, United States.
Sue BigginsBasic Sciences Division, Howard Hughes Medical Institute, Fred Hutchinson Cancer Center, Seattle, WA 98109, United States.ORCID 0000-0002-4499-6319

Funding

Translational Bioimaging Core Shared ResourceP30CA015704 · NCI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI Eric Collisson · 1985 to 2026
$296.4M
Reconstitution and biophysical study of chromosome segregation machineryR35GM134842 · NIGMS · UNIVERSITY OF WASHINGTON · PI Charles L Asbury · 2020 to 2026
$4.7M
Mechanisms underlying chromosome segregationR35GM149357 · NIGMS · FRED HUTCHINSON CANCER CENTER · PI Susan Biggins · 2023 to 2026
$1.5M
Elucidating the mechanisms of kinetochore assembly initiationF32GM136010 · NIGMS · FRED HUTCHINSON CANCER RESEARCH CENTER · PI POPCHOCK, ANDREW R · 2020 to 2021
$131k
HHS P30 CA015704/CA/NCIHoward Hughes Medical InstituteJane Coffin Childs Memorial FundNCI NIH HHS P30 CA015704NIGMS NIH HHS F32 GM136010NIGMS NIH HHS R35 GM134842NIGMS NIH HHS R35 GM149357NIH HHS F32GM136010NIH HHS R35 GM149357/GM/NIGMS
6 · The paper itself

Abstract

Kinetochores are megadalton protein machines that harness microtubules to segregate chromosomes during cell division. The kinetochores must assemble after DNA replication during every cell cycle onto specialized regions of chromosomes called centromeres, but the order and regulation of their assembly remains unclear due to the complexity of kinetochore composition and the difficulty resolving individual kinetochores in vivo. Here, by adapting a prior single-molecule method for monitoring kinetochore assembly in budding yeast lysates, we identify a sequential order of assembly and uncover previously unknown interdependencies between subcomplexes. We show that inner kinetochore assembly depends partly on outer kinetochore components, and that outer kinetochore branches do not assemble independently of one another. Notably, Mif2 assembly is a rate-limiting step that can be accelerated by binding to the Mtw1 subcomplex, thereby promoting rapid assembly of many inner and outer kinetochore components. The importance of controlling kinetochore assembly kinetics is supported by a Mif2 mutant lacking both autoinhibition and Mtw1 subcomplex binding activity, which leads to defective kinetochore-microtubule attachments when the centromeric histone variant Cse4 is overexpressed. Altogether, our work provides a direct view of kinetochore assembly and reveals highly interdependent regulatory events that control its order and timing.

Indexed as

CentromereKinetochoresSaccharomyces cerevisiae ProteinsCell Cycle ProteinsChromosomal Proteins, Non-HistoneDNA-Binding ProteinsMicrotubulesProtein BindingSaccharomyces cerevisiaeCell Cycle ProteinsChromosomal Proteins, Non-HistoneCSE4 protein, S cerevisiaeDNA-Binding ProteinsMIF2 protein, S cerevisiaeMTW1 protein, S cerevisiaeSaccharomyces cerevisiae Proteins

Identifiers

PMID41099706
PMCPMC12526914

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.