Evidence map›Paper›PMID 23589891›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2013

Phosphoregulation promotes release of kinetochores from dynamic microtubules via multiple mechanisms.

Krishna K Sarangapani, Bungo Akiyoshi, Nicole M Duggan, Sue Biggins, Charles L Asbury

Abstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers.

0numbers the graph read from it
0cells of the map it votes in
68citing 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

68 citing papers in PubMed.

  1. Review
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  14. Mechanical coupling coordinates microtubule growth.bioRxiv : the preprint server for biology · 2023
    Article
  15. Article
  16. Article
  17. Article
  18. Article
  19. Review
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8 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors.

Krishna K SarangapaniDepartment of Physiology and Biophysics, University of Washington, Seattle, WA 98195, USA.
Bungo Akiyoshi
Nicole M Duggan
Sue Biggins
Charles L Asbury

Funding

EXPERIMENTAL PATHOLOGY OF CARDIOVASCULAR DISEASET32HL007312 · NHLBI · UNIVERSITY OF WASHINGTON · PI MAJESKY, MARK W., SCHWARTZ, STEPHEN MARK · 1985 to 2019
$11.8M
Regulation of Chromosome SegregationR01GM064386 · NIGMS · FRED HUTCHINSON CANCER RESEARCH CENTER · PI BIGGINS, SUSAN · 2002 to 2022
$7.2M
Supplement to Biophysical Study of Reconstituted Kinetochore-microtubule AttachmentsR01GM079373 · NIGMS · UNIVERSITY OF WASHINGTON · PI ASBURY, CHARLES · 2006 to 2019
$4.5M
NHLBI NIH HHS T32 HL007312NHLBI NIH HHS T32HL007312NIGMS NIH HHS R01 GM064386NIGMS NIH HHS R01GM064386NIGMS NIH HHS R01 GM079373NIGMS NIH HHS R01GM079373
6 · The paper itself

Abstract

During mitosis, multiprotein complexes called kinetochores orchestrate chromosome segregation by forming load-bearing attachments to dynamic microtubule tips, and by participating in phosphoregulatory error correction. The conserved kinase Aurora B phosphorylates the major microtubule-binding kinetochore subcomplexes, Ndc80 and (in yeast) Dam1, to promote release of erroneous attachments, giving another chance for proper attachments to form. It is unknown whether Aurora B phosphorylation promotes release directly, by increasing the rate of kinetochore detachment, or indirectly, by destabilizing the microtubule tip. Moreover, the relative importance of phosphorylation of Ndc80 vs. Dam1 in the context of whole kinetochores is unclear. To address these uncertainties, we isolated native yeast kinetochore particles carrying phosphomimetic mutations on Ndc80 and Dam1, and applied advanced laser-trapping techniques to measure the strength and stability of their attachments to individual dynamic microtubule tips. Rupture forces were reduced by phosphomimetic mutations on both subcomplexes, in an additive manner, indicating that both subcomplexes make independent contributions to attachment strength. Phosphomimetics on either subcomplex reduced attachment lifetimes under constant force, primarily by accelerating detachment during microtubule growth. Phosphomimetics on Dam1 also increased the likelihood of switches from microtubule growth into shortening, further promoting release in an indirect manner. Taken together, our results suggest that, in vivo, Aurora B releases kinetochores via at least two mechanisms: by weakening the kinetochore-microtubule interface and also by destabilizing the kinetochore-attached microtubule tip.

Indexed as

Biomechanical PhenomenaKineticsKinetochoresMicrotubulesMolecular MimicryMultiprotein ComplexesMutationPhosphorylationPhosphoserineProtein KinasesSaccharomyces cerevisiaeSaccharomyces cerevisiae ProteinsMultiprotein ComplexesPhosphoserineProtein KinasesSaccharomyces cerevisiae Proteins

Identifiers

PMID23589891
PMCPMC3645574

What OpenQuestion holds

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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.