Evidence map›Paper›PMID 28373564›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2017

CMG-Pol epsilon dynamics suggests a mechanism for the establishment of leading-strand synthesis in the eukaryotic replisome.

Jin Chuan Zhou, Agnieszka Janska, Panchali Goswami, Ludovic Renault, Ferdos Abid Ali, Abhay Kotecha, John F X Diffley, Alessandro Costa

Open access · bronzeAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2017. 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
6.5field-weighted citation impact, top 2% 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

68 citing papers in PubMed, 106 citations in OpenAlex.

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  6. 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
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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

8 authors at 2 institutions in 1 country.

Jin Chuan ZhouMacromolecular Machines Laboratory, The Francis Crick Institute, London, NW1 1AT, United Kingdom.ORCID 0000-0001-5716-5170
Agnieszka JanskaChromosome Replication Laboratory, The Francis Crick Institute, London, NW1 1AT, United Kingdom.
Panchali GoswamiMacromolecular Machines Laboratory, The Francis Crick Institute, London, NW1 1AT, United Kingdom.
Ludovic RenaultMacromolecular Machines Laboratory, The Francis Crick Institute, London, NW1 1AT, United Kingdom.
Ferdos Abid AliMacromolecular Machines Laboratory, The Francis Crick Institute, London, NW1 1AT, United Kingdom.
Abhay KotechaDivision of Structural Biology, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, OX3 7BN, United Kingdom.
John F X DiffleyChromosome Replication Laboratory, The Francis Crick Institute, London, NW1 1AT, United Kingdom.ORCID 0000-0001-5184-7680
Alessandro CostaMacromolecular Machines Laboratory, The Francis Crick Institute, London, NW1 1AT, United Kingdom; alessandro.costa@crick.ac.uk.
The Francis Crick Institute · GBCentre for Human Genetics · GB

Funding

Biotechnology and Biological Sciences Research CouncilCancer Research UK 15669Cancer Research UK 15852Medical Research CouncilWellcome Trust 060208/Z/00/ZWellcome Trust 093305/Z/10/ZWellcome Trust 106252/Z/14/Z
6 · The paper itself

Abstract

The replisome unwinds and synthesizes DNA for genome duplication. In eukaryotes, the Cdc45-MCM-GINS (CMG) helicase and the leading-strand polymerase, Pol epsilon, form a stable assembly. The mechanism for coupling DNA unwinding with synthesis is starting to be elucidated, however the architecture and dynamics of the replication fork remain only partially understood, preventing a molecular understanding of chromosome replication. To address this issue, we conducted a systematic single-particle EM study on multiple permutations of the reconstituted CMG-Pol epsilon assembly. Pol epsilon contains two flexibly tethered lobes. The noncatalytic lobe is anchored to the motor of the helicase, whereas the polymerization domain extends toward the side of the helicase. We observe two alternate configurations of the DNA synthesis domain in the CMG-bound Pol epsilon. We propose that this conformational switch might control DNA template engagement and release, modulating replisome progression.

Indexed as

DNA ReplicationDNA HelicasesDNA Polymerase IIEukaryotic CellsSaccharomyces cerevisiaeSaccharomyces cerevisiae ProteinsDNA HelicasesDNA Polymerase IISaccharomyces cerevisiae ProteinsCMG helicaseDNA polymeraseDNA replicationsingle-particle electron microscopy

Identifiers

PMID28373564
PMCPMC5402455
OpenAlexW2604825272

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.