Evidence map›Paper›PMID 37820732›Full record

ArticleMolecular cell2023

The structural mechanism of dimeric DONSON in replicative helicase activation.

Milos A Cvetkovic, Paolo Passaretti, Agata Butryn, Alicja Reynolds-Winczura, Georgia Kingsley, Aggeliki Skagia, Cyntia Fernandez-Cuesta, Divyasree Poovathumkadavil, Roger George, Anoop S Chauhan and 4 more

Open access · hybridAbstract read
In one paragraph

Article in Molecular cell, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.

0numbers the graph read from it
0cells of the map it votes in
29citing papers in PubMed
6.3field-weighted citation impact, top 3% 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

29 citing papers in PubMed, 41 citations in OpenAlex.

  1. Article
  2. Article
  3. DONSON links tumor-cell survival to MIF-associated macrophage remodeling in small cell lung cancer.Apoptosis : an international journal on programmed cell death · 2026
    Article
  4. Article
  5. Article
  6. Meier-Gorlin syndrome due to a recurrentJournal of pediatric endocrinology & metabolism : JPEM · 2026
    Article
  7. Article
  8. Article
  9. Xenopus laevis Egg Extracts.Methods in molecular biology (Clifton, N.J.) · 2026
    Article
  10. Article
  11. Article
  12. Article
  13. Structure of the Saccharolobus solfataricus GINS tetramer.Acta crystallographica. Section F, Structural biology communications · 2025
    Article
  14. Article
  15. Review
  16. Article
  17. Article
  18. Review
  19. 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

14 authors at 2 institutions in 1 country.

Milos A CvetkovicMacromolecular Machines Laboratory, The Francis Crick Institute, London NW1 1AT, UK.
Paolo PassarettiInstitute of Cancer and Genomic Sciences, Birmingham Centre for Genome Biology, University of Birmingham, Birmingham B15 2TT, UK.
Agata ButrynMacromolecular Machines Laboratory, The Francis Crick Institute, London NW1 1AT, UK.
Alicja Reynolds-WinczuraInstitute of Cancer and Genomic Sciences, Birmingham Centre for Genome Biology, University of Birmingham, Birmingham B15 2TT, UK.
Georgia KingsleyInstitute of Cancer and Genomic Sciences, Birmingham Centre for Genome Biology, University of Birmingham, Birmingham B15 2TT, UK.
Aggeliki SkagiaInstitute of Cancer and Genomic Sciences, Birmingham Centre for Genome Biology, University of Birmingham, Birmingham B15 2TT, UK.
Cyntia Fernandez-CuestaInstitute of Cancer and Genomic Sciences, Birmingham Centre for Genome Biology, University of Birmingham, Birmingham B15 2TT, UK.
Divyasree PoovathumkadavilInstitute of Cancer and Genomic Sciences, Birmingham Centre for Genome Biology, University of Birmingham, Birmingham B15 2TT, UK.
Roger GeorgeStructural Biology Science Technology Platform, The Francis Crick Institute, London NW1 1AT, UK.
Anoop S ChauhanInstitute of Cancer and Genomic Sciences, Birmingham Centre for Genome Biology, University of Birmingham, Birmingham B15 2TT, UK.
Satpal S JhujhInstitute of Cancer and Genomic Sciences, Birmingham Centre for Genome Biology, University of Birmingham, Birmingham B15 2TT, UK.
Grant S StewartInstitute of Cancer and Genomic Sciences, Birmingham Centre for Genome Biology, University of Birmingham, Birmingham B15 2TT, UK.
Agnieszka GambusInstitute of Cancer and Genomic Sciences, Birmingham Centre for Genome Biology, University of Birmingham, Birmingham B15 2TT, UK. Electronic address: a.gambus@bham.ac.uk.
Alessandro CostaMacromolecular Machines Laboratory, The Francis Crick Institute, London NW1 1AT, UK. Electronic address: alessandro.costa@crick.ac.uk.
University of Birmingham · GBThe Francis Crick Institute · GB

Funding

Cancer Research UK CC2009European Research CouncilMedical Research Council MR/W001152/1Wellcome Trust 215510Wellcome Trust FC001065
6 · The paper itself

Abstract

The MCM motor of the replicative helicase is loaded onto origin DNA as an inactive double hexamer before replication initiation. Recruitment of activators GINS and Cdc45 upon S-phase transition promotes the assembly of two active CMG helicases. Although work with yeast established the mechanism for origin activation, how CMG is formed in higher eukaryotes is poorly understood. Metazoan Downstream neighbor of Son (DONSON) has recently been shown to deliver GINS to MCM during CMG assembly. What impact this has on the MCM double hexamer is unknown. Here, we used cryoelectron microscopy (cryo-EM) on proteins isolated from replicating Xenopus egg extracts to identify a double CMG complex bridged by a DONSON dimer. We find that tethering elements mediating complex formation are essential for replication. DONSON reconfigures the MCM motors in the double CMG, and primordial dwarfism patients' mutations disrupting DONSON dimerization affect GINS and MCM engagement in human cells and DNA synthesis in Xenopus egg extracts.

Indexed as

Cell Cycle ProteinsDNA HelicasesNuclear ProteinsAnimalsCryoelectron MicroscopyDNADNA ReplicationEnzyme ActivationHumansMinichromosome Maintenance ProteinsSaccharomyces cerevisiaeCell Cycle ProteinsDNADNA HelicasesDONSON protein, humanMinichromosome Maintenance ProteinsNuclear Proteinscryo-EMDNA replication initiationDONSONprimordial dwarfismreplicative helicaseXenopus egg extract

Identifiers

PMID37820732
PMCPMC7616792
OpenAlexW4387475681

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.