Evidence map›Paper›PMID 42049237›Full record

ArticleNucleic acids research2026

K63-linked ubiquitylation of S2P-RNAPII regulates transcription in a DNAPK inter-dependent manner in response to double-strand breaks.

Vasiliki Pantazi, Paul Smith, Zoltan G Pahi, Manuela Katona, Adam Pap, Zsuzsanna Darula, Roman Fischer, Iolanda Vendrell, Benedikt M Kessler, Marcel A T M van Vugt and 2 more

Abstract read
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In one paragraph

Article in Nucleic acids research, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

12 authors.

Vasiliki PantaziGenome Integrity and DNA Repair Core Group, Hungarian Centre of Excellence for Molecular Medicine (HCEMM), Szeged H-6728, Hungary.
Paul SmithThe Institute of Genetics and Cancer, University of Edinburgh, Edinburgh EH4 2XU, United Kingdom.
Zoltan G PahiGenome Integrity and DNA Repair Core Group, Hungarian Centre of Excellence for Molecular Medicine (HCEMM), Szeged H-6728, Hungary.
Manuela KatonaGenome Integrity and DNA Repair Core Group, Hungarian Centre of Excellence for Molecular Medicine (HCEMM), Szeged H-6728, Hungary.
Adam PapSingle Cell Omics Advanced Core Facility, Hungarian Centre of Excellence for Molecular Medicine (HCEMM), Szeged H-6728, Hungary.
Zsuzsanna DarulaSingle Cell Omics Advanced Core Facility, Hungarian Centre of Excellence for Molecular Medicine (HCEMM), Szeged H-6728, Hungary.
Roman FischerTarget Discovery Institute, Centre for Medicines Discovery, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7FZ, United Kingdom.
Iolanda VendrellTarget Discovery Institute, Centre for Medicines Discovery, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7FZ, United Kingdom.
Benedikt M KesslerTarget Discovery Institute, Centre for Medicines Discovery, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7FZ, United Kingdom.
Marcel A T M van VugtDepartment of Medical Oncology, University Medical Center Groningen, University of Groningen, Groningen 9713GZ, The Netherlands.
Vincenzo D'AngiolellaThe Institute of Genetics and Cancer, University of Edinburgh, Edinburgh EH4 2XU, United Kingdom.
Tibor PankotaiGenome Integrity and DNA Repair Core Group, Hungarian Centre of Excellence for Molecular Medicine (HCEMM), Szeged H-6728, Hungary.ORCID 0000-0001-9810-5465

Funding

Dutch Cancer Society 15919EU's Horizon 2020 739593Medical Research Council MR/X006980/1Ministry of Culture and Innovation of Hungary 2022-2.1.1-NLMinistry of Culture and Innovation of Hungary 2022-2.1.1-NL-2022-00005Ministry of Culture and Innovation of Hungary TKP2021-EGAMinistry of Culture and Innovation of Hungary TKP-2021-EGA-05National Research, Development and Innovation Office NKFI-FK 132080University of SzegedUniversity of Szeged Open Access Fund 8490
6 · The paper itself

Abstract

DNA double-strand breaks (DSBs) are highly toxic DNA lesions that can lead to genomic instability. DSBs can also interfere with other DNA-based processes, including transcription, and thereby jeopardizing cellular function. In situations of persistent DSBs, RNA polymerase II (RNAPII) needs to be removed to facilitate DNA repair. DSB-induced RNAPII removal involves multifaceted ubiquitylation, but the mechanisms involved remain elusive. Our data show that in response to DSBs, the E3 ubiquitin ligase NEDD4, and to a lesser extent CRL3 complexes, catalyse the ubiquitylation of elongating RNAPII, facilitating efficient DSB repair. Specifically, NEDD4 is identified as the specific writer of K63-linked ubiquitin chains on Serine2 phosphorylated (S2P)-RNAPII under stress, while the total pool of RNAPII is found to be modified mainly with K48-linked ubiquitin chains. We find that the ubiquitin ligases NEDD4, WWP2, and CUL3-based complexes exhibit a DNAPK inter-dependency, driving NHEJ repair and proper resolution of transcription defects caused by DSBs.

Indexed as

DNA Breaks, Double-StrandedRNA Polymerase IITranscription, GeneticUbiquitinationCullin ProteinsDNA End-Joining RepairHumansLysineNedd4 Ubiquitin Protein LigasesPhosphorylationUbiquitin-Protein LigasesCullin ProteinsLysineNedd4 protein, humanNedd4 Ubiquitin Protein LigasesRNA Polymerase IIUbiquitin-Protein Ligases

Identifiers

PMID42049237
PMCPMC13122179

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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.