Evidence map›Paper›PMID 33657379›Full record

ArticleCell reports2021

Topological stress is responsible for the detrimental outcomes of head-on replication-transcription conflicts.

Kevin S Lang, Houra Merrikh

Open access · goldAbstract read
In one paragraph

Article in Cell reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.

0numbers the graph read from it
0cells of the map it votes in
32citing papers in PubMed
2.0field-weighted citation impact, top 13% 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

32 citing papers in PubMed, 43 citations in OpenAlex.

  1. Review
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  11. Transcription-Replication Conflicts: Unlocking New Frontiers in Cancer.BioEssays : news and reviews in molecular, cellular and developmental biology · 2025
    Review
  12. Review
  13. Article
  14. Review
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  16. Kinetic Features of Degradation of R-Loops by RNase H1 fromInternational journal of molecular sciences · 2024
    Article
  17. Article
  18. Review
  19. Review
  20. Review
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

2 authors at 1 institution in 1 country.

Kevin S LangDepartment of Biochemistry, Light Hall, Vanderbilt University, Nashville, TN, USA.
Houra MerrikhDepartment of Biochemistry, Light Hall, Vanderbilt University, Nashville, TN, USA. Electronic address: houra.merrikh@vanderbilt.edu.
Vanderbilt University · US

Funding

INTERDISCIPLINARY PROGRAM IN BACTERIAL PATHOGENESIST32AI055396 · NIAID · UNIVERSITY OF WASHINGTON · PI FANG, FERRIC C · 2003 to 2019
$2.8M
Targeted Gene Evolution via Replication-Transcription ConflictsDP2GM110773 · NIGMS · UNIVERSITY OF WASHINGTON · PI MERRIKH, HOURA · 2013 to 2013
$2.2M
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 AI140557NIAID NIH HHS T32 AI055396NIGMS NIH HHS DP2 GM110773NIGMS NIH HHS R01 GM128191
6 · The paper itself

Abstract

Conflicts between the replication and transcription machineries have profound effects on chromosome duplication, genome organization, and evolution across species. Head-on conflicts (lagging-strand genes) are significantly more detrimental than codirectional conflicts (leading-strand genes). The fundamental reason for this difference is unknown. Here, we report that topological stress significantly contributes to this difference. We find that head-on, but not codirectional, conflict resolution requires the relaxation of positive supercoils by the type II topoisomerases DNA gyrase and Topo IV, at least in the Gram-positive model bacterium Bacillus subtilis. Interestingly, our data suggest that after positive supercoil resolution, gyrase introduces excessive negative supercoils at head-on conflict regions, driving pervasive R-loop formation. Altogether, our results reveal a fundamental mechanistic difference between the two types of encounters, addressing a long-standing question in the field of replication-transcription conflicts.

Indexed as

DNA ReplicationGene Expression Regulation, BacterialTranscription, GeneticBacillus subtilisBacterial ProteinsDNA, BacterialDNA-Directed RNA PolymerasesDNA GyraseDNA, SuperhelicalDNA Topoisomerase IVDNA Topoisomerases, Type IINucleic Acid ConformationStress, MechanicalStructure-Activity RelationshipBacterial ProteinsDNA, BacterialDNA-Directed RNA PolymerasesDNA GyraseDNA, SuperhelicalDNA Topoisomerase IVDNA Topoisomerases, Type IIDNA supercoilingReplication-transcription conflictsR-loopsType II topoisomerases

Identifiers

PMID33657379
PMCPMC7986047
OpenAlexW3135727438

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.