Evidence map›Paper›PMID 29489749›Full record

ArticleNature2018

The mechanism of eukaryotic CMG helicase activation.

Max E Douglas, Ferdos Abid Ali, Alessandro Costa, John F X Diffley

Abstract read
In one paragraph

Article in Nature, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 177 papers.

0numbers the graph read from it
0cells of the map it votes in
177citing papers in PubMed
13.2field-weighted citation impact, top 1% 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

177 citing papers in PubMed, 278 citations in OpenAlex.

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  20. Structure of the Saccharolobus solfataricus GINS tetramer.Acta crystallographica. Section F, Structural biology communications · 2025
    Article

117 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

4 authors at 1 institution in 1 country.

Max E DouglasChromosome Replication 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.
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 · GB

Funding

Cancer Research UK 15669Cancer Research UK 15852Medical Research Council FC001065Medical Research Council FC001066Wellcome Trust 106252Wellcome Trust FC001065Wellcome Trust FC001066
6 · The paper itself

Abstract

The initiation of eukaryotic DNA replication occurs in two discrete stages: first, the minichromosome maintenance (MCM) complex assembles as a head-to-head double hexamer that encircles duplex replication origin DNA during G1 phase; then, 'firing factors' convert each double hexamer into two active Cdc45-MCM-GINS helicases (CMG) during S phase. This second stage requires separation of the two origin DNA strands and remodelling of the double hexamer so that each MCM hexamer encircles a single DNA strand. Here we show that the MCM complex, which hydrolyses ATP during double-hexamer formation, remains stably bound to ADP in the double hexamer. Firing factors trigger ADP release, and subsequent ATP binding promotes stable CMG assembly. CMG assembly is accompanied by initial DNA untwisting and separation of the double hexamer into two discrete but inactive CMG helicases. Mcm10, together with ATP hydrolysis, then triggers further DNA untwisting and helicase activation. After activation, the two CMG helicases translocate in an 'N terminus-first' direction, and in doing so pass each other within the origin; this requires that each helicase is bound entirely to single-stranded DNA. Our experiments elucidate the mechanism of eukaryotic replicative helicase activation, which we propose provides a fail-safe mechanism for bidirectional replisome establishment.

Indexed as

DNA ReplicationAdenosine DiphosphateAdenosine TriphosphateCell Cycle ProteinsDNA-Binding ProteinsDNA HelicasesDNA, Single-StrandedEnzyme ActivationEnzyme StabilityMinichromosome Maintenance ProteinsNucleic Acid ConformationReplication OriginSaccharomyces cerevisiaeSaccharomyces cerevisiae ProteinsAdenosine DiphosphateAdenosine TriphosphateCell Cycle ProteinsDNA-Binding ProteinsDNA HelicasesDNA, Single-StrandedMinichromosome Maintenance ProteinsSaccharomyces cerevisiae Proteins

Identifiers

PMID29489749
PMCPMC6847044
OpenAlexW2787975097

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.