Evidence map›Paper›PMID 26275776›Full record

ArticleNucleic acids research2015

The WRN exonuclease domain protects nascent strands from pathological MRE11/EXO1-dependent degradation.

Chiara Iannascoli, Valentina Palermo, Ivana Murfuni, Annapaola Franchitto, Pietro Pichierri

Open access · goldAbstract read
In one paragraph

Article in Nucleic acids research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.

0numbers the graph read from it
0cells of the map it votes in
59citing papers in PubMed
4.5field-weighted citation impact, top 5% 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

59 citing papers in PubMed, 85 citations in OpenAlex.

  1. Article
  2. Article
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  4. Article
  5. The function of Mgs1/WRNIP1 in genome maintenance.Frontiers in molecular biosciences · 2026
    Review
  6. Review
  7. Review
  8. PLK1 phosphorylates WRN at replication forks.The Journal of pharmacology and experimental therapeutics · 2025
    Article
  9. Article
  10. Article
  11. Article
  12. RAD52 prevents accumulation ofbioRxiv : the preprint server for biology · 2024
    Article
  13. Review
  14. Review
  15. Article
  16. Article
  17. Article
  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

5 authors at 1 institution in 1 country.

Chiara IannascoliSection of Experimental and Computational Carcinogenesis, Department of Environment and Primary Prevention, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy.
Valentina PalermoSection of Experimental and Computational Carcinogenesis, Department of Environment and Primary Prevention, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy.
Ivana MurfuniSection of Experimental and Computational Carcinogenesis, Department of Environment and Primary Prevention, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy.
Annapaola FranchittoSection of Molecular Epidemiology, Department of Environment and Primary Prevention, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy.
Pietro PichierriSection of Experimental and Computational Carcinogenesis, Department of Environment and Primary Prevention, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy pietro.pichierri@iss.it.
Istituto Superiore di Sanità · IT

Funding

Telethon GGP12144
6 · The paper itself

Abstract

The WRN helicase/exonuclease protein is required for proper replication fork recovery and maintenance of genome stability. However, whether the different catalytic activities of WRN cooperate to recover replication forks in vivo is unknown. Here, we show that, in response to replication perturbation induced by low doses of the TOP1 inhibitor camptothecin, loss of the WRN exonuclease resulted in enhanced degradation and ssDNA formation at nascent strands by the combined action of MRE11 and EXO1, as opposed to the limited processing of nascent strands performed by DNA2 in wild-type cells. Nascent strand degradation by MRE11/EXO1 took place downstream of RAD51 and affected the ability to resume replication, which correlated with slow replication rates in WRN exonuclease-deficient cells. In contrast, loss of the WRN helicase reduced exonucleolytic processing at nascent strands and led to severe genome instability. Our findings identify a novel role of the WRN exonuclease at perturbed forks, thus providing the first in vivo evidence for a distinct action of the two WRN enzymatic activities upon fork stalling and providing insights into the pathological mechanisms underlying the processing of perturbed forks.

Indexed as

DNA ReplicationCamptothecinCell Line, TransformedDNA-Binding ProteinsDNA HelicasesDNA, Single-StrandedExodeoxyribonucleasesGenomic InstabilityHumansMutationPoly(ADP-ribose) PolymerasesProtein Structure, TertiaryRecQ HelicasesTopoisomerase I InhibitorsCamptothecinDNA-Binding ProteinsDNA HelicasesDNA, Single-Strandedexodeoxyribonuclease IExodeoxyribonucleasesPoly(ADP-ribose) PolymerasesRecQ HelicasesTopoisomerase I Inhibitors

Identifiers

PMID26275776
PMCPMC4787784
OpenAlexW1825467031

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.