Evidence map›Paper›PMID 36864174›Full record

ArticleNature structural & molecular biology2023

Direct visualization of transcription-replication conflicts reveals post-replicative DNA:RNA hybrids.

Henriette Stoy, Katharina Zwicky, Danina Kuster, Kevin S Lang, Jana Krietsch, Magdalena P Crossley, Jonas A Schmid, Karlene A Cimprich, Houra Merrikh, Massimo Lopes

Open access · hybridFull text read
In one paragraph

Article in Nature structural & molecular biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.

0numbers the graph read from it
0cells of the map it votes in
53citing papers in PubMed
10.8field-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

53 citing papers in PubMed, 72 citations in OpenAlex.

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  17. Deaminase Modulation Driving a New Era in Drug Development.International journal of molecular sciences · 2025
    Review
  18. Article
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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

10 authors at 4 institutions in 2 countries.

Henriette StoyInstitute of Molecular Cancer Research, University of Zurich, Zurich, Switzerland.ORCID 0000-0002-2943-414X
Katharina Zwicky *Institute of Molecular Cancer Research, University of Zurich, Zurich, Switzerland.
Danina Kuster *Institute of Molecular Cancer Research, University of Zurich, Zurich, Switzerland.
Kevin S LangVanderbilt University School of Medicine, Nashville, TN, USA.
Jana KrietschInstitute of Molecular Cancer Research, University of Zurich, Zurich, Switzerland.
Magdalena P CrossleyDepartment of Chemical and Systems Biology, Stanford University School of Medicine, Stanford, CA, USA.
Jonas A SchmidInstitute of Molecular Cancer Research, University of Zurich, Zurich, Switzerland.ORCID 0000-0003-1791-1874
Karlene A CimprichDepartment of Chemical and Systems Biology, Stanford University School of Medicine, Stanford, CA, USA.ORCID 0000-0002-1937-2969
Houra MerrikhVanderbilt University School of Medicine, Nashville, TN, USA.ORCID 0000-0001-9956-9640
Massimo LopesInstitute of Molecular Cancer Research, University of Zurich, Zurich, Switzerland. lopes@imcr.uzh.ch.ORCID 0000-0003-3847-8133
University of Zurich · CHStanford University · USUniversity of Minnesota · USVanderbilt University · US

Funding

Transcription-Associated Genome InstabilityR01GM119334 · NIGMS · STANFORD UNIVERSITY · PI Karlene A Cimprich · 2016 to 2026
$4.0M
Replication resolved in the living cell: Replisome dynamics, stability and structure.R01GM128191 · NIGMS · VANDERBILT UNIVERSITY · PI MERRIKH, HOURA, WIGGINS, PAUL A · 2018 to 2021
$1.4M
The impact of replication-transcription conflicts on bacterial pathogenesisF32AI140557 · NIAID · VANDERBILT UNIVERSITY · PI LANG, KEVIN S · 2018 to 2020
$130k
NIAID NIH HHS F32 AI140557NIGMS NIH HHS R01 GM119334NIGMS NIH HHS R01 GM128191
6 · The paper itself

Abstract

Transcription-replication collisions (TRCs) are crucial determinants of genome instability. R-loops were linked to head-on TRCs and proposed to obstruct replication fork progression. The underlying mechanisms, however, remained elusive due to the lack of direct visualization and of non-ambiguous research tools. Here, we ascertained the stability of estrogen-induced R-loops on the human genome, visualized them directly by electron microscopy (EM), and measured R-loop frequency and size at the single-molecule level. Combining EM and immuno-labeling on locus-specific head-on TRCs in bacteria, we observed the frequent accumulation of DNA:RNA hybrids behind replication forks. These post-replicative structures are linked to fork slowing and reversal across conflict regions and are distinct from physiological DNA:RNA hybrids at Okazaki fragments. Comet assays on nascent DNA revealed a marked delay in nascent DNA maturation in multiple conditions previously linked to R-loop accumulation. Altogether, our findings suggest that TRC-associated replication interference entails transactions that follow initial R-loop bypass by the replication fork.

Indexed as

DNA ReplicationRNAChromosomesDNADNA-Binding ProteinsGenomic InstabilityHumansDNADNA-Binding ProteinsRNA

Identifiers

PMID36864174
PMCPMC10023573
OpenAlexW4322766156

What OpenQuestion holds

Textfull text, public
LicenceCC BY
measurements read177
identifiers read1
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.