Evidence map›Paper›PMID 42230924›Full record

ArticleNature cell biology2026

Nucleophagy removes cytotoxic trapped PARP1.

Gwendoline Hoslett, Sara Tribble, Pauline Lascaux, Stelios Koukouravas, Ignacio Torrecilla, Wei Song, Cynthia X Hou, Junyi Li, Martín González-Fernández, Giuliana De Gregoriis and 14 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature cell biology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Article
  2. Article
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

24 authors.

Gwendoline HoslettThe MRC Weatherall Institute of Molecular Medicine, Department of Oncology, John Radcliffe Hospital, University of Oxford, Oxford, UK.
Sara TribbleThe MRC Weatherall Institute of Molecular Medicine, Department of Oncology, John Radcliffe Hospital, University of Oxford, Oxford, UK.
Pauline LascauxThe MRC Weatherall Institute of Molecular Medicine, Department of Oncology, John Radcliffe Hospital, University of Oxford, Oxford, UK.
Stelios KoukouravasThe MRC Weatherall Institute of Molecular Medicine, Department of Oncology, John Radcliffe Hospital, University of Oxford, Oxford, UK.
Ignacio TorrecillaThe MRC Weatherall Institute of Molecular Medicine, Department of Oncology, John Radcliffe Hospital, University of Oxford, Oxford, UK.ORCID http://orcid.org/0000-0003-4283-0283
Wei SongThe MRC Weatherall Institute of Molecular Medicine, Department of Oncology, John Radcliffe Hospital, University of Oxford, Oxford, UK.ORCID http://orcid.org/0000-0002-2834-5671
Cynthia X HouThe MRC Weatherall Institute of Molecular Medicine, Department of Oncology, John Radcliffe Hospital, University of Oxford, Oxford, UK.
Junyi LiThe MRC Weatherall Institute of Molecular Medicine, Department of Oncology, John Radcliffe Hospital, University of Oxford, Oxford, UK.
Martín González-FernándezInstitute of Animal Pathology, Vetsuisse Faculty, University of Bern, Bern, Switzerland.ORCID http://orcid.org/0009-0006-8308-5493
Giuliana De GregoriisDepartment of Oncology, University of Oxford, Oxford, UK.ORCID http://orcid.org/0000-0002-7857-0658
Rebecca A DaggDepartment of Oncology, University of Oxford, Oxford, UK.ORCID http://orcid.org/0000-0002-3023-9616
Darragh O'BrienCentre for Medicines Discovery, Nuffield Department of Medicine, University of Oxford, Oxford, UK.ORCID http://orcid.org/0000-0003-4924-7795
Andrea PierangeliniCentre for Medicines Discovery, Nuffield Department of Medicine, University of Oxford, Oxford, UK.ORCID http://orcid.org/0009-0009-9396-619X
Thibaud MartialCentre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
Alvin Wei Tian NgPopulation and Global Health Programme, Lee Kong Chian School of Medicine (LKCMedicine), Nanyang Technological University, Singapore, Singapore.
Nuno RaimundoDepartment of Cell and Molecular Systems, Penn State College of Medicine, and Penn State Cancer Institute, Hershey, PA, USA.ORCID http://orcid.org/0000-0002-5988-9129
Ira MilosevicCentre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK.ORCID http://orcid.org/0000-0001-6440-3763
Raimundo FreireUnidad de Investigación, Hospital Universitario de Canarias, Instituto de Investigación Sanitaria de Canarias (IISC)/FIISC, La Laguna, Spain.ORCID http://orcid.org/0000-0003-4473-8894
Yuliang LiDepartment of Interventional Medicine and Minimally Invasive Oncology, The Second Qilu Hospital of Shandong University, Jinan, P. R. China.
Sven RottenbergInstitute of Animal Pathology, Vetsuisse Faculty, University of Bern, Bern, Switzerland.ORCID http://orcid.org/0000-0003-2044-9844
Dragomir B KrastevPrecision Oncology Laboratory, The Breast Cancer Now Toby Robins Research Centre, The Institute of Cancer Research, London, UK.ORCID http://orcid.org/0000-0003-4298-7272
Christopher J LordPrecision Oncology Laboratory, The Breast Cancer Now Toby Robins Research Centre, The Institute of Cancer Research, London, UK.ORCID http://orcid.org/0000-0002-3226-0515
Madalena TarsounasDepartment of Oncology, University of Oxford, Oxford, UK.ORCID http://orcid.org/0000-0002-4273-2870
Kristijan RamadanThe MRC Weatherall Institute of Molecular Medicine, Department of Oncology, John Radcliffe Hospital, University of Oxford, Oxford, UK. kristijan.ramadan@ntu.edu.sg.ORCID http://orcid.org/0000-0001-5522-021X

Funding

Breast Cancer Now (BCN) 2022.11PR1570Cancer Research UK (CRUK) DRCPGM\100001Fonds National de la Recherche Luxembourg (National Research Fund) 14548187Ministry of Education - Singapore (MOE) 023917-00001RCUK | Biotechnology and Biological Sciences Research Council (BBSRC) BB/T008784/1RCUK | Medical Research Council (MRC) MR/X006409/1RCUK | Medical Research Council (MRC) StudentshipSwiss National Science Foundation | nccr - on the move (National Center of Competence in Research - The Migration-Mobility Nexus) 320030M_219453Wellcome TrustWellcome Trust (Wellcome) 224361/Z/21/Z
6 · The paper itself

Abstract

Poly(ADP-ribose) polymerase (PARP) inhibitors (PARPi) induce cytotoxicity in homologous recombination repair (HR)-deficient (HRD) cancers by trapping PARP1 on chromatin, thereby causing irreparable replication-associated DNA damage. Although increased clearance of trapped PARP1 from chromatin reduces the sensitivity of cancer cells to PARPi, details surrounding this process remain unclear. PARPi exposure is known to cause increased autophagy flux, whereas autophagy inhibition can hypersensitize cells to PARPi. Our study reveals that trapped PARP1 is cleared via nucleophagy, with the selective autophagy receptor TEX264 and its partner segregase p97 (also known as VCP) orchestrating this process. TEX264 interacts directly with trapped PARP1, linking it to the autophagosomal protein LC3 for degradation. Disrupting this pathway, either chemically or genetically, increases PARP1 trapping, resulting in protein aggregates, DNA damage and cell lethality, ultimately re-sensitizing PARPi-resistant cells. We conclude that nucleophagy serves a cytoprotective role by targeting PARPi-induced trapped PARP1 for degradation.

Indexed as

AutophagyPoly (ADP-Ribose) Polymerase-1Poly(ADP-ribose) Polymerase InhibitorsAnimalsCell Cycle ProteinsCell Line, TumorDNA DamageHumansMicrotubule-Associated ProteinsProteolysisValosin Containing ProteinCell Cycle ProteinsMAP1LC3A protein, humanMicrotubule-Associated ProteinsPARP1 protein, humanPoly (ADP-Ribose) Polymerase-1Poly(ADP-ribose) Polymerase InhibitorsValosin Containing Protein

Identifiers

PMID42230924
PMCPMC13278974

What OpenQuestion holds

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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.