Evidence map›Paper›PMID 37781931›Full record

ArticleThe EMBO journal2023

Replication-induced DNA secondary structures drive fork uncoupling and breakage.

Sophie L Williams, Corella S Casas-Delucchi, Federica Raguseo, Dilek Guneri, Yunxuan Li, Masashi Minamino, Emma E Fletcher, Joseph Tp Yeeles, Ulrich F Keyser, Zoë Ae Waller and 2 more

Open access · hybridAbstract read
In one paragraph

Article in The EMBO journal, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.

0numbers the graph read from it
0cells of the map it votes in
34citing papers in PubMed
7.7field-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

34 citing papers in PubMed, 50 citations in OpenAlex.

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  18. Centromeres drive and take a break.Chromosome research : an international journal on the molecular, supramolecular and evolutionary aspects of chromosome biology · 2025
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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 6 institutions in 1 country.

Sophie L WilliamsGenome Replication Lab, Division of Cancer Biology, Institute of Cancer Research, Chester Beatty Laboratories, London, UK.ORCID 0000-0002-8796-9185
Corella S Casas-DelucchiGenome Replication Lab, Division of Cancer Biology, Institute of Cancer Research, Chester Beatty Laboratories, London, UK.ORCID 0000-0003-2531-1123
Federica RaguseoChemistry Department, Imperial College London, MSRH, London, UK.ORCID 0000-0001-9397-5496
Dilek GuneriUCL, School of Pharmacy, London, UK.ORCID 0000-0003-0858-1746
Yunxuan LiCavendish Laboratory, University of Cambridge, Cambridge, UK.ORCID 0009-0005-8362-5173
Masashi MinaminoFrancis Crick Institute, London, UK.ORCID 0000-0002-9521-5906
Emma E FletcherMRC Laboratory of Molecular Biology, Cambridge, UK.ORCID 0000-0002-0792-5212
Joseph Tp YeelesMRC Laboratory of Molecular Biology, Cambridge, UK.ORCID 0000-0002-2255-2119
Ulrich F KeyserCavendish Laboratory, University of Cambridge, Cambridge, UK.ORCID 0000-0003-3188-5414
Zoë Ae WallerUCL, School of Pharmacy, London, UK.ORCID 0000-0001-8538-0484
Marco Di AntonioChemistry Department, Imperial College London, MSRH, London, UK.ORCID 0000-0002-7321-1867
Gideon CosterGenome Replication Lab, Division of Cancer Biology, Institute of Cancer Research, Chester Beatty Laboratories, London, UK.ORCID 0000-0002-1449-6655
Institute of Cancer Research · GBMRC Laboratory of Molecular Biology · GBThe Francis Crick Institute · GBThe London College · GBUniversity of Cambridge · GBMorgan Stanley (United Kingdom) · GB

Funding

Biotechnology and Biological Sciences Research Council BB/R011605/1Biotechnology and Biological Sciences Research Council BB/W001616/1Cancer Research UK 15671Medical Research Council MC_UP_1201/12Wellcome TrustWellcome Trust 210470/Z/18/Z
6 · The paper itself

Abstract

Sequences that form DNA secondary structures, such as G-quadruplexes (G4s) and intercalated-Motifs (iMs), are abundant in the human genome and play various physiological roles. However, they can also interfere with replication and threaten genome stability. Multiple lines of evidence suggest G4s inhibit replication, but the underlying mechanism remains unclear. Moreover, evidence of how iMs affect the replisome is lacking. Here, we reconstitute replication of physiologically derived structure-forming sequences to find that a single G4 or iM arrest DNA replication. Direct single-molecule structure detection within solid-state nanopores reveals structures form as a consequence of replication. Combined genetic and biophysical characterisation establishes that structure stability and probability of structure formation are key determinants of replisome arrest. Mechanistically, replication arrest is caused by impaired synthesis, resulting in helicase-polymerase uncoupling. Significantly, iMs also induce breakage of nascent DNA. Finally, stalled forks are only rescued by a specialised helicase, Pif1, but not Rrm3, Sgs1, Chl1 or Hrq1. Altogether, we provide a mechanism for quadruplex structure formation and resolution during replication and highlight G4s and iMs as endogenous sources of replication stress.

Indexed as

DNAG-QuadruplexesDNA ReplicationGenome, HumanHumansNucleotidyltransferasesDNANucleotidyltransferasesDNA replicationDNA secondary structuresgenome stabilityG-quadruplex and i-Motifreplication stress

Identifiers

PMID37781931
PMCPMC10646557
OpenAlexW4387242024

What OpenQuestion holds

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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.