Evidence map›Paper›PMID 22581055›Full record

ArticleNature cell biology2012

Recruitment of the human Cdt1 replication licensing protein by the loop domain of Hec1 is required for stable kinetochore-microtubule attachment.

Dileep Varma, Srikripa Chandrasekaran, Lynsie J R Sundin, Karen T Reidy, Xiaohu Wan, Dawn A D Chasse, Kathleen R Nevis, Jennifer G DeLuca, E D Salmon, Jeanette Gowen Cook

Abstract read
In one paragraph

Article in Nature cell biology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers.

0numbers the graph read from it
0cells of the map it votes in
65citing papers in PubMed
4.1field-weighted citation impact, top 6% 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

65 citing papers in PubMed, 104 citations in OpenAlex.

  1. Structure and function of the outer kinetochore.Nature reviews. Molecular cell biology · 2026
    Review
  2. Article
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  5. The Crk4-Cyc4 complex regulates GThe EMBO journal · 2024
    Article
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  19. Phospho-regulation of mitotic spindle assembly.Cytoskeleton (Hoboken, N.J.) · 2020
    Review
  20. Review

5 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors at 4 institutions in 1 country.

Dileep VarmaDepartment of Biology, University of North Carolina, Chapel Hill, North Carolina 27599, USA.
Srikripa Chandrasekaran
Lynsie J R Sundin
Karen T Reidy
Xiaohu Wan
Dawn A D Chasse
Kathleen R Nevis
Jennifer G DeLuca
E D Salmon
Jeanette Gowen Cook
University of North Carolina at Chapel Hill · USColorado State University · USDuke Medical Center · USMassachusetts General Hospital · US

Funding

Virology Research Program (Program 4)P30CA016086 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Deborah F. Tate · 1985 to 2026
$201.5M
MECHANISMS OF MITOTIC SPINDLE ASSEMBLY AND FUNCTIONR37GM024364 · NIGMS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI SALMON, EDWARD D. · 2004 to 2013
$4.1M
MECHANISMS OF MITOTIC SPINDLE ASSEMBLY AND FUNCTIONR01GM024364 · NIGMS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI BLOOM, KERRY S, SALMON, EDWARD D. · 1985 to 2018
$3.1M
Kinetochore Function in Vertebrate CellsR01GM088371 · NIGMS · COLORADO STATE UNIVERSITY · PI DELUCA, JENNIFER G · 2010 to 2018
$3.1M
Replication Licensing and the Cell CycleR01GM083024 · NIGMS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI COOK, JEANETTE GOWEN · 2009 to 2020
$2.9M
Pre-replication complex formation in mammalian cellsK01CA094907 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI COOK, JEANETTE GOWEN · 2003 to 2007
$741k
NCI NIH HHS K01 CA094907NCI NIH HHS P30 CA016086NIGMS NIH HHS GM083024NIGMS NIH HHS GM088371NIGMS NIH HHS GM24364NIGMS NIH HHS R01 GM024364NIGMS NIH HHS R01 GM083024NIGMS NIH HHS R01 GM088371NIGMS NIH HHS R37 GM024364
6 · The paper itself

Abstract

Cdt1, a protein critical for replication origin licensing in G1 phase, is degraded during S phase but re-accumulates in G2 phase. We now demonstrate that human Cdt1 has a separable essential mitotic function. Cdt1 localizes to kinetochores during mitosis through interaction with the Hec1 component of the Ndc80 complex. G2-specific depletion of Cdt1 arrests cells in late prometaphase owing to abnormally unstable kinetochore-microtubule (kMT) attachments and Mad1-dependent spindle-assembly-checkpoint activity. Cdt1 binds a unique loop extending from the rod domain of Hec1 that we show is also required for kMT attachment. Mutation of the loop domain prevents Cdt1 kinetochore localization and arrests cells in prometaphase. Super-resolution fluorescence microscopy indicates that Cdt1 binding to the Hec1 loop domain promotes a microtubule-dependent conformational change in the Ndc80 complex in vivo. These results support the conclusion that Cdt1 binding to Hec1 is essential for an extended Ndc80 configuration and stable kMT attachment.

Indexed as

Amino Acid SequenceCell Cycle CheckpointsCell Cycle ProteinsCytoskeletal ProteinsHeLa CellsHumansKinetochoresMicrotubulesMitosisMolecular Sequence DataNuclear ProteinsCDT1 protein, humanCell Cycle ProteinsCytoskeletal ProteinsNDC80 protein, humanNuclear Proteins

Identifiers

PMID22581055
PMCPMC3366049
OpenAlexW1975153105

What OpenQuestion holds

Textmetadata
LicenceTDM
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.