Evidence map›Paper›PMID 33651990›Full record

ArticleCurrent biology : CB2021

Kinetochore stretching-mediated rapid silencing of the spindle-assembly checkpoint required for failsafe chromosome segregation.

Kazuhiko S K Uchida, Minji Jo, Kota Nagasaka, Motoko Takahashi, Norihisa Shindo, Katsushi Shibata, Kozo Tanaka, Hiroshi Masumoto, Tatsuo Fukagawa, Toru Hirota

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In one paragraph

Article in Current biology : CB, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
2.0field-weighted citation impact, top 15% of its field
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

20 citing papers in PubMed, 24 citations in OpenAlex.

  1. Review
  2. Structure and function of the outer kinetochore.Nature reviews. Molecular cell biology · 2026
    Review
  3. Article
  4. Article
  5. Article
  6. Review
  7. Principles and dynamics of spindle assembly checkpoint signalling.Nature reviews. Molecular cell biology · 2023
    Review
  8. Double-checking chromosome segregation.The Journal of cell biology · 2023
    Review
  9. Review
  10. Article
  11. Kinetochore Architecture Employs Diverse Linker Strategies Across Evolution.Frontiers in cell and developmental biology · 2022
    Review
  12. The microtubule- and PP1-binding activities ofMolecular biology of the cell · 2022
    Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. Spindle assembly checkpoint activation and silencing at kinetochores.Seminars in cell & developmental biology · 2021
    Review
  18. Review
  19. Review
  20. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors at 5 institutions in 1 country.

Kazuhiko S K UchidaDivision of Experimental Pathology, Cancer Institute of the Japanese Foundation for Cancer Research, Tokyo, Japan; Division of Functional Genomics, Faculty of Pharmaceutical Sciences, Himeji Dokkyo University, Himeji, Japan.
Minji JoDivision of Experimental Pathology, Cancer Institute of the Japanese Foundation for Cancer Research, Tokyo, Japan.
Kota NagasakaDivision of Experimental Pathology, Cancer Institute of the Japanese Foundation for Cancer Research, Tokyo, Japan.
Motoko TakahashiDivision of Experimental Pathology, Cancer Institute of the Japanese Foundation for Cancer Research, Tokyo, Japan.
Norihisa ShindoDivision of Experimental Pathology, Cancer Institute of the Japanese Foundation for Cancer Research, Tokyo, Japan.
Katsushi ShibataDivision of Functional Genomics, Faculty of Pharmaceutical Sciences, Himeji Dokkyo University, Himeji, Japan.
Kozo TanakaDepartment of Molecular Oncology, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan.
Hiroshi MasumotoLaboratory of Chromosome Engineering, Kazusa DNA Research Institute, Kisarazu, Japan.
Tatsuo FukagawaLaboratory of Chromosome Biology, Graduate School of Frontier Biosciences, Osaka University, Osaka, Japan.
Toru HirotaDivision of Experimental Pathology, Cancer Institute of the Japanese Foundation for Cancer Research, Tokyo, Japan. Electronic address: thirota@jfcr.or.jp.
Japanese Foundation For Cancer Research · JPHimeji Dokkyo University · JPKazusa DNA Research Institute · JPThe University of Osaka · JPTohoku University · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The spindle-assembly checkpoint facilitates mitotic fidelity by delaying anaphase onset in response to microtubule vacancy at kinetochores. Following microtubule attachment, kinetochores receive microtubule-derived force, which causes kinetochores to undergo repetitive cycles of deformation; this phenomenon is referred to as kinetochore stretching. The nature of the forces and the relevance relating this deformation are not well understood. Here, we show that kinetochore stretching occurs within a framework of single end-on attached kinetochores, irrespective of microtubule poleward pulling force. An experimental method to conditionally interfere with the stretching allowed us to determine that kinetochore stretching comprises an essential process of checkpoint silencing by promoting PP1 phosphatase recruitment after the establishment of end-on attachments and removal of the majority of checkpoint-activating kinase Mps1 from kinetochores. Remarkably, we found that a lower frequency of kinetochore stretching largely correlates with a prolonged metaphase in cancer cell lines with chromosomal instability. Perturbation of kinetochore stretching and checkpoint silencing in chromosomally stable cells produced anaphase bridges, which can be alleviated by reducing chromosome-loaded cohesin. These observations indicate that kinetochore stretching-mediated checkpoint silencing provides an unanticipated etiology underlying chromosomal instability and underscores the importance of a rapid metaphase-to-anaphase transition in sustaining mitotic fidelity.

Indexed as

Chromosome SegregationKinetochoresM Phase Cell Cycle CheckpointsSpindle ApparatusAnaphaseCell Line, TumorChromosomal InstabilityHumansMicrotubulesanaphase bridgescancerCENP-Tchromosomal instabilityKnl1metaphase-to-anaphase transitionmitotic checkpointMps1PP1

Identifiers

PMID33651990
OpenAlexW3135568890

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.