Evidence map›Paper›PMID 37855233›Full record

ArticleThe EMBO journal2023

RNase H2 degrades toxic RNA:DNA hybrids behind stalled forks to promote replication restart.

Jonathan Heuzé, Samira Kemiha, Antoine Barthe, Alba Torán Vilarrubias, Elyès Aouadi, Umberto Aiello, Domenico Libri, Yea-Lih Lin, Armelle Lengronne, Jérôme Poli and 1 more

Open access · greenAbstract 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 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
3.4field-weighted citation impact, top 7% 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

16 citing papers in PubMed, 22 citations in OpenAlex.

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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

11 authors at 1 institution in 2 countries.

Jonathan Heuzé *Institut de Génétique Humaine, Université de Montpellier, CNRS, Equipe labélisée Ligue contre le Cancer, Montpellier, France.ORCID 0009-0008-2870-521X
Samira Kemiha *Institut de Génétique Humaine, Université de Montpellier, CNRS, Equipe labélisée Ligue contre le Cancer, Montpellier, France.ORCID 0000-0001-8405-6957
Antoine BartheInstitut de Génétique Humaine, Université de Montpellier, CNRS, Equipe labélisée Ligue contre le Cancer, Montpellier, France.
Alba Torán VilarrubiasInstitut de Génétique Humaine, Université de Montpellier, CNRS, Equipe labélisée Ligue contre le Cancer, Montpellier, France.
Elyès AouadiInstitut de Génétique Humaine, Université de Montpellier, CNRS, Equipe labélisée Ligue contre le Cancer, Montpellier, France.
Umberto AielloUniversité Paris Cité, CNRS, Institut Jacques Monod, Paris, France.
Domenico LibriUniversité Paris Cité, CNRS, Institut Jacques Monod, Paris, France.ORCID 0000-0001-6728-0594
Yea-Lih LinInstitut de Génétique Humaine, Université de Montpellier, CNRS, Equipe labélisée Ligue contre le Cancer, Montpellier, France.ORCID 0000-0003-4063-0771
Armelle LengronneInstitut de Génétique Humaine, Université de Montpellier, CNRS, Equipe labélisée Ligue contre le Cancer, Montpellier, France.ORCID 0000-0002-3140-7968
Jérôme PoliInstitut de Génétique Humaine, Université de Montpellier, CNRS, Equipe labélisée Ligue contre le Cancer, Montpellier, France.ORCID 0000-0001-8091-5507
Philippe PaseroInstitut de Génétique Humaine, Université de Montpellier, CNRS, Equipe labélisée Ligue contre le Cancer, Montpellier, France.ORCID 0000-0001-5891-0822
Centre National de la Recherche Scientifique · FR

Funding

Agence Nationale de la Recherche (ANR) ANR-16-CE12-0022-01Agence Nationale de la Recherche (ANR) ANR-17-EURE-0013Agence Nationale de la Recherche (ANR) ANR-18-IDEX-0001Agence Nationale de la Recherche (ANR) ANR-19-CE12-0016-01Agence Nationale de la Recherche (ANR) ANR-19-CE12-0023-03Agence Nationale de la Recherche (ANR) ANR-20-CE12-0016-01Agence Nationale de la Recherche (ANR) ANR-21-CE12-0040-01Agence Nationale de la Recherche (ANR) ANR-22-CE12-0031-01Centre National de la Recherche Scientifique (CNRS)Fondation ARC pour la Recherche sur le Cancer (ARC)Fondation pour la Recherche Médicale (FRM)French Ministry of Research and Higher EducationInstitut Universitaire de France (IUF)
6 · The paper itself

Abstract

R-loops represent a major source of replication stress, but the mechanism by which these structures impede fork progression remains unclear. To address this question, we monitored fork progression, arrest, and restart in Saccharomyces cerevisiae cells lacking RNase H1 and H2, two enzymes responsible for degrading RNA:DNA hybrids. We found that while RNase H-deficient cells could replicate their chromosomes normally under unchallenged growth conditions, their replication was impaired when exposed to hydroxyurea (HU) or methyl methanesulfonate (MMS). Treated cells exhibited increased levels of RNA:DNA hybrids at stalled forks and were unable to generate RPA-coated single-stranded (ssDNA), an important postreplicative intermediate in resuming replication. Similar impairments in nascent DNA resection and ssDNA formation at HU-arrested forks were observed in human cells lacking RNase H2. However, fork resection was fully restored by addition of triptolide, an inhibitor of transcription that induces RNA polymerase degradation. Taken together, these data indicate that RNA:DNA hybrids not only act as barriers to replication forks, but also interfere with postreplicative fork repair mechanisms if not promptly degraded by RNase H.

Indexed as

DNA ReplicationRNADNAHumansHydroxyureaRibonuclease HRibonucleasesDNAHydroxyureaRibonuclease HRibonucleasesRNAreplication stressR-loopsRNase Htranscription-replication conflicts

Identifiers

PMID37855233
PMCPMC10690446
OpenAlexW4387764895

What Socratic holds

Textmetadata
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 Socratic graph.