Evidence map›Paper›PMID 42269607›Full record

ArticleCell2026

DNA repair drives cisplatin-induced neuronal death.

William J Nathan, Chuanyuan Chen, Rosy Sakr, Bruno Siqueira Mietto, Vincent van Batenburg, Jeroen van den Berg, Josette J Wlaschin, Ferenc Livak, Elsa Callen, Nancy Wong and 14 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. Review
  2. Article
  3. 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.

William J NathanLaboratory of Genome Integrity, National Cancer Institute, NIH, Bethesda, MD 20892, USA.
Chuanyuan ChenLaboratory of Genome Integrity, National Cancer Institute, NIH, Bethesda, MD 20892, USA.
Rosy SakrLaboratory of Genome Integrity, National Cancer Institute, NIH, Bethesda, MD 20892, USA.
Bruno Siqueira MiettoSection on the Development of Neurodegeneration, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Bethesda, MD 20892, USA; Institute of Biological Sciences, Federal University of Juiz de Fora, Juiz de Fora, 36036-900 MG, Brazil.
Vincent van BatenburgOncode Institute, Hubrecht Institute-KNAW (Royal Netherlands Academy of Arts and Sciences) and University Medical Center Utrecht, 3584 CT Utrecht, the Netherlands.
Jeroen van den BergOncode Institute, Hubrecht Institute-KNAW (Royal Netherlands Academy of Arts and Sciences) and University Medical Center Utrecht, 3584 CT Utrecht, the Netherlands.
Josette J WlaschinSection on the Development of Neurodegeneration, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Bethesda, MD 20892, USA.
Ferenc LivakLaboratory of Genome Integrity, National Cancer Institute, NIH, Bethesda, MD 20892, USA.
Elsa CallenLaboratory of Genome Integrity, National Cancer Institute, NIH, Bethesda, MD 20892, USA.
Nancy WongLaboratory of Genome Integrity, National Cancer Institute, NIH, Bethesda, MD 20892, USA.
Eliza Y H LloydSection on the Development of Neurodegeneration, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Bethesda, MD 20892, USA.
Hanna SilberbergSection on the Development of Neurodegeneration, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Bethesda, MD 20892, USA.
Sushma SharmaDepartment of Medical Biochemistry and Biophysics, Umeå University, Umeå 90187, Sweden.
Raj ChariGenome Modification Core, Laboratory Animal Sciences Program, Frederick National Laboratory for Cancer Research, Frederick, MD 21701, USA.
Tzipporah FreemanCenter for ViroScience and Cure, Department of Pediatrics, School of Medicine, Emory University, Atlanta, GA 30322, USA.
Baek KimCenter for ViroScience and Cure, Department of Pediatrics, School of Medicine, Emory University, Atlanta, GA 30322, USA.
Alexander van OudenaardenOncode Institute, Hubrecht Institute-KNAW (Royal Netherlands Academy of Arts and Sciences) and University Medical Center Utrecht, 3584 CT Utrecht, the Netherlands.
Alexander T CheslerNational Center for Complementary and Integrative Health, NIH, Bethesda, MD 20892, USA.
Michael E WardNational Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD 20892, USA.
Lisa D BoxerLaboratory of Genome Integrity, National Cancer Institute, NIH, Bethesda, MD 20892, USA.
Peter J McHughDepartment of Oncology, MRC Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DS, UK.
Andrei ChabesDepartment of Medical Biochemistry and Biophysics, Umeå University, Umeå 90187, Sweden.
Claire E Le PichonSection on the Development of Neurodegeneration, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Bethesda, MD 20892, USA.
André NussenzweigLaboratory of Genome Integrity, National Cancer Institute, NIH, Bethesda, MD 20892, USA. Electronic address: nussenza@exchange.nih.gov.

Funding

DNA RepairZIABC010283 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI NUSSENZWEIG, ANDRE A. · 2009 to 2025
$27.0M
Relationship between DNA damage detection and signalingZIABC010959 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI NUSSENZWEIG, ANDRE A. · 2009 to 2025
$27.0M
The neuronal stress response in neurodegenerative disease and painZIAHD008966 · NICHD · EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT · PI LE PICHON, CLAIRE · 2017 to 2025
$17.1M
NATIONAL INSTITUTE OF HEALTH (NIH), NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES (NCATS), BESPOKE GENE THERAPY CONSORTIUM - COORDINATION CENTER75N98022D00019 · OD · BLACK CANYON CONSULTING LLC · 2022 to 2025
$6.9M
Lentivirus Replication Strategy and PathogenesisR01AI136581 · NIAID · EMORY UNIVERSITY · PI Baek Kim · 2018 to 2026
$3.9M
DNA REPAIRZ01BC010283 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI NUSSENZWEIG, ANDRE A. · 1998 to 2008
$2.9M
SAMHD1 mediated dNTP regulation and HIV in myeloid cellsR01AI162633 · NIAID · EMORY UNIVERSITY · PI Baek Kim · 2021 to 2026
$2.7M
Relationship between DNA damage detection and signalingZ01BC010959 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI NUSSENZWEIG, ANDRE A. · 2008 to 2008
$812k
Intramural NIH HHS Z01 BC010283Intramural NIH HHS Z01 BC010959Intramural NIH HHS Z99 CA999999Intramural NIH HHS ZIA BC010283Intramural NIH HHS ZIA BC010959Intramural NIH HHS ZIA HD008966NCI NIH HHS HHSN261201500003CNCI NIH HHS HHSN261201500003INIAID NIH HHS R01 AI136581NIAID NIH HHS R01 AI162633NIH HHS 75N98022D00019
6 · The paper itself

Abstract

Platinum agents are cornerstone therapies for many cancers but often cause neurotoxicity in post-mitotic tissues, for which effective interventions are lacking. This limitation reflects an incomplete understanding of neuronal responses to DNA damage. We show that nucleotide excision repair (NER) mediates cisplatin lesion removal in neurons; however, unlike its protective role in dividing cells, NER promotes neuronal death in response to cisplatin. This vulnerability arises because neurons possess low deoxynucleoside triphosphate (dNTP) pools. dNTPs are initially consumed during transcription-coupled NER to resolve transcription-blocking lesions. As dNTP levels become depleted, repair fails to complete, leading to accumulation of double-strand breaks, particularly during global-genome NER. Supplementation with deoxynucleosides or genetic upregulation of dNTP synthesis restores nucleotide pools, protects neurons from cell death, and reduces cisplatin-induced neuropathic pain. These findings identify limited dNTP availability as a key vulnerability in post-mitotic cells and suggest nucleoside supplementation as a potential strategy to mitigate chemotherapy-induced neurotoxicity.

Indexed as

CisplatinDNA RepairNeuronsAnimalsAntineoplastic AgentsCell DeathDeoxyribonucleotidesDNA Breaks, Double-StrandedDNA DamageExcision RepairHumansMiceAntineoplastic AgentsCisplatinDeoxyribonucleotideschemotherapycisplatindeoxynucleotidesDNA repairneuronneuropathyneurotoxicitynucleotide excision repair

Identifiers

PMID42269607
PMCPMC13411057

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.