Evidence map›Paper›PMID 40219969›Full record

ArticleNucleic acids research2025

Oxidative stress at telomeres triggers internal DNA loops, TRF1 dissociation, and TRF2-dependent R-loops.

Trang Thu Nguyen, Giulia Mazzucco, Eftychia Kyriacou, Thomas Lunardi, Leona Brandl, Wareed Ahmed, Ylli Doksani, Joachim Lingner

Abstract read
In one paragraph

Article in Nucleic acids research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed, 1 pooled it
–field-weighted citation impact
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

12 citing papers in PubMed, 1 synthesis or guideline pooled it.

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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

8 authors.

Trang Thu NguyenSwiss Institute for Experimental Cancer Research (ISREC), School of Life Sciences, École Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland.
Giulia MazzuccoIFOM ETS - The AIRC Institute of Molecular Oncology, 20139 Milan, Italy.
Eftychia KyriacouSwiss Institute for Experimental Cancer Research (ISREC), School of Life Sciences, École Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland.
Thomas LunardiSwiss Institute for Experimental Cancer Research (ISREC), School of Life Sciences, École Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland.
Leona BrandlSwiss Institute for Experimental Cancer Research (ISREC), School of Life Sciences, École Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland.ORCID 0009-0009-2632-6897
Wareed AhmedSwiss Institute for Experimental Cancer Research (ISREC), School of Life Sciences, École Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland.
Ylli DoksaniIFOM ETS - The AIRC Institute of Molecular Oncology, 20139 Milan, Italy.
Joachim LingnerSwiss Institute for Experimental Cancer Research (ISREC), School of Life Sciences, École Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland.ORCID 0000-0002-2853-5803

Funding

Associazione Italiana per la Ricerca sul Cancro IG 28954Concern Foundation Conquer CancerEuropean Commission Seventh Framework Programme 812829Initial Training Network (ITN)NARNational Centre of Competence in Research 205601Peter and Traudl Engelhorn Stiftung 532515Swiss National Science Foundation 310030_214833
6 · The paper itself

Abstract

Telomeres are the nucleoprotein structures at chromosome ends. Telomeres are particularly sensitive to oxidative stress, which can induce telomere damage, shortening, and premature cellular senescence. How oxidative damage influences telomere structure has not been defined. Here, we induce oxidative damage at telomeres using menadione, which damages mitochondria mimicking intrinsic oxidative stress. We find that oxidative stress induces at telomeres single-stranded DNA breaks, internal DNA loop structures, dissociation of the shelterin component TRF1, upregulation of TERRA long noncoding RNA, and increased DNA:RNA hybrid structures known as R-loops. R-loop formation is enhanced not only in cis at telomeres, which show increased TERRA transcription, but also in trans at telomeres at which TERRA transcription is not induced indicating post-transcriptional R-loop formation. Finally, we show that oxidative damage induced R-loop formation requires TRF2, whose R-loop promoting activity may be unleashed upon TRF1 dissociation from telomeres. Altogether, our findings uncover in response to oxidative stress major remodelling of telomeric DNA, RNA, and shelterin complexes, and they unravel a physiological role of TRF2's ability to stimulate TERRA R-loop formation. We propose that the identified structural changes may facilitate DNA damage signalling and repair pathways to maintain telomere integrity during development and aging.

Indexed as

Oxidative StressR-Loop StructuresTelomereTelomeric Repeat Binding Protein 1Telomeric Repeat Binding Protein 2DNADNA DamageHumansRNA, Long NoncodingShelterin ComplexVitamin K 3DNARNA, Long NoncodingShelterin ComplexTelomeric Repeat Binding Protein 1Telomeric Repeat Binding Protein 2TERF2 protein, humanVitamin K 3

Identifiers

PMID40219969
PMCPMC11992676

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Registered trials

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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.