Evidence map›Paper›PMID 28643783›Full record

ArticleNature communications2017

Cdt1 stabilizes an open MCM ring for helicase loading.

Jordi Frigola, Jun He, Kerstin Kinkelin, Valerie E Pye, Ludovic Renault, Max E Douglas, Dirk Remus, Peter Cherepanov, Alessandro Costa, John F X Diffley

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.

0numbers the graph read from it
0cells of the map it votes in
59citing papers in PubMed
3.6field-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

59 citing papers in PubMed, 94 citations in OpenAlex.

  1. Article
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  7. Compact Origins and Where to Find Them: ORC's Guide to Genome-Wide Licensing.BioEssays : news and reviews in molecular, cellular and developmental biology · 2025
    Review
  8. Review
  9. Article
  10. Review
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  15. Article
  16. Heliyon · 2024
    Article
  17. Article
  18. Article
  19. Regulation of replication origin licensing by ORC phosphorylation reveals a two-step mechanism for Mcm2-7 ring closing.Proceedings of the National Academy of Sciences of the United States of America · 2023
    Article
  20. Article
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

10 authors at 2 institutions in 2 countries.

Jordi FrigolaChromosome Replication Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.
Jun HeChromosome Replication Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.
Kerstin KinkelinChromosome Replication Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.
Valerie E PyeChromatin Structure and Mobile DNA Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.ORCID 0000-0001-9616-2992
Ludovic RenaultMacromolecular Machines Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.ORCID 0000-0001-6464-8808
Max E DouglasChromosome Replication Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.
Dirk RemusMolecular Biology Program, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, New York 10065, USA.
Peter CherepanovChromatin Structure and Mobile DNA Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.
Alessandro CostaMacromolecular Machines Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.
John F X DiffleyChromosome Replication Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.
The Francis Crick Institute · GBMemorial Sloan Kettering Cancer Center · US

Funding

Cancer Research UK 15669Cancer Research UK 15852Wellcome Trust FC001061Wellcome Trust FC001065Wellcome Trust FC001066
6 · The paper itself

Abstract

ORC, Cdc6 and Cdt1 act together to load hexameric MCM, the motor of the eukaryotic replicative helicase, into double hexamers at replication origins. Here we show that Cdt1 interacts with MCM subunits Mcm2, 4 and 6, which both destabilizes the Mcm2-5 interface and inhibits MCM ATPase activity. Using X-ray crystallography, we show that Cdt1 contains two winged-helix domains in the C-terminal half of the protein and a catalytically inactive dioxygenase-related N-terminal domain, which is important for MCM loading, but not for subsequent replication. We used these structures together with single-particle electron microscopy to generate three-dimensional models of MCM complexes. These show that Cdt1 stabilizes MCM in a left-handed spiral open at the Mcm2-5 gate. We propose that Cdt1 acts as a brace, holding MCM open for DNA entry and bound to ATP until ORC-Cdc6 triggers ATP hydrolysis by MCM, promoting both Cdt1 ejection and MCM ring closure.

Indexed as

Adenosine TriphosphateCell Cycle ProteinsCross-Linking ReagentsCrystallography, X-RayDNA-Binding ProteinsDNA, FungalDNA HelicasesDNA ReplicationHydrolysisMicroscopy, ElectronMinichromosome Maintenance ProteinsModels, MolecularOrigin Recognition ComplexProtein ConformationProtein DomainsReplication OriginAdenosine TriphosphateCell Cycle ProteinsCross-Linking ReagentsDNA-Binding ProteinsDNA, FungalDNA HelicasesMinichromosome Maintenance ProteinsOrigin Recognition ComplexSaccharomyces cerevisiae ProteinsTAH11 protein, S cerevisiae

Identifiers

PMID28643783
PMCPMC5490006
OpenAlexW2625839772

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.