Evidence map›Paper›PMID 30498216›Full record

ArticleNature communications2018

Structure of DNA-CMG-Pol epsilon elucidates the roles of the non-catalytic polymerase modules in the eukaryotic replisome.

Panchali Goswami, Ferdos Abid Ali, Max E Douglas, Julia Locke, Andrew Purkiss, Agnieszka Janska, Patrik Eickhoff, Anne Early, Andrea Nans, Alan M C Cheung and 2 more

Open access · greenAbstract read
In one paragraph

Article in Nature communications, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 79 papers.

0numbers the graph read from it
0cells of the map it votes in
79citing 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

79 citing papers in PubMed, 84 citations in OpenAlex.

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  15. The proofreading mechanism of the human leading-strand DNA polymerase ε holoenzyme.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  16. Review
  17. Article
  18. Article
  19. Article
  20. Clamping Pol ε to the leading strand.Nature structural & molecular biology · 2024
    Article

19 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

12 authors at 1 institution in 1 country.

Panchali GoswamiMacromolecular Machines Laboratory, The Francis Crick Institute, 1 Midland Road, London, NW1 1AT, UK.
Ferdos Abid AliMacromolecular Machines Laboratory, The Francis Crick Institute, 1 Midland Road, London, NW1 1AT, UK.
Max E DouglasChromosome Replication Laboratory, The Francis Crick Institute, 1 Midland Road, London, NW1 1AT, UK.
Julia LockeMacromolecular Machines Laboratory, The Francis Crick Institute, 1 Midland Road, London, NW1 1AT, UK.
Andrew PurkissStructural Biology Science Technology Platform, The Francis Crick Institute, 1 Midland Road, London, NW1 1AT, UK.
Agnieszka JanskaChromosome Replication Laboratory, The Francis Crick Institute, 1 Midland Road, London, NW1 1AT, UK.
Patrik EickhoffMacromolecular Machines Laboratory, The Francis Crick Institute, 1 Midland Road, London, NW1 1AT, UK.
Anne EarlyChromosome Replication Laboratory, The Francis Crick Institute, 1 Midland Road, London, NW1 1AT, UK.
Andrea NansStructural Biology Science Technology Platform, The Francis Crick Institute, 1 Midland Road, London, NW1 1AT, UK.
Alan M C CheungDepartment of Structural and Molecular Biology, Institute of Structural and Molecular Biology, University College London, London, UK.ORCID http://orcid.org/0000-0001-6430-5127
John F X DiffleyChromosome Replication 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. alessandro.costa@crick.ac.uk.
The Francis Crick Institute · GB

Funding

Wellcome Trust FC001065Wellcome Trust FC001066
6 · The paper itself

Abstract

Eukaryotic origin firing depends on assembly of the Cdc45-MCM-GINS (CMG) helicase. A key step is the recruitment of GINS that requires the leading-strand polymerase Pol epsilon, composed of Pol2, Dpb2, Dpb3, Dpb4. While a truncation of the catalytic N-terminal Pol2 supports cell division, Dpb2 and C-terminal Pol2 (C-Pol2) are essential for viability. Dpb2 and C-Pol2 are non-catalytic modules, shown or predicted to be related to an exonuclease and DNA polymerase, respectively. Here, we present the cryo-EM structure of the isolated C-Pol2/Dpb2 heterodimer, revealing that C-Pol2 contains a DNA polymerase fold. We also present the structure of CMG/C-Pol2/Dpb2 on a DNA fork, and find that polymerase binding changes both the helicase structure and fork-junction engagement. Inter-subunit contacts that keep the helicase-polymerase complex together explain several cellular phenotypes. At least some of these contacts are preserved during Pol epsilon-dependent CMG assembly on path to origin firing, as observed with DNA replication reconstituted in vitro.

Indexed as

Adaptor Proteins, Signal TransducingCell Cycle ProteinsDNADNA-Binding ProteinsDNA Polymerase IIDNA ReplicationHumansNuclear ProteinsProtein Structure, TertiaryAdaptor Proteins, Signal TransducingCDC45 protein, humanCell Cycle ProteinsDNADNA-Binding ProteinsDNA Polymerase IIMCMBP protein, humanNuclear Proteins

Identifiers

PMID30498216
PMCPMC6265327
OpenAlexW2900902074

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.