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DNA repair drives cisplatin-induced neuronal death.

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Paper

Loaded from Europe PMC by your browser, not stored by OSCR: doi.org · Europe PMC

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The authors' code

Rust · 76 lines · 2.8 KB · GPL-3.0

  1. use std::env;
  2. use std::process::Command;
  3. use std::time::{SystemTime, UNIX_EPOCH};
  5. fn git_short_hash() -> String {
  6. Command::new("git")
  7. .args(["rev-parse", "--short", "HEAD"])
  8. .output()
  9. .ok()
  10. .filter(|o| o.status.success())
  11. .and_then(|o| String::from_utf8(o.stdout).ok())
  12. .map(|s| s.trim().to_string())
  13. .filter(|s| !s.is_empty())
  14. .unwrap_or_else(|| "unknown".to_string())
  15. }
  17. fn build_epoch() -> u64 {
  18. match env::var("SOURCE_DATE_EPOCH") {
  19. // .trim() absorbs whitespace from shell expansions like
  20. // `SOURCE_DATE_EPOCH="$(git log -1 --format=%ct) "`; sign/format
  21. // strictness (no leading `+`, no underscores, no hex) is preserved.
  22. Ok(s) => s.trim().parse::<u64>().unwrap_or_else(|_| {
  23. panic!(
  24. "SOURCE_DATE_EPOCH must be a non-negative decimal seconds-since-epoch integer, got {s:?}"
  25. )
  26. }),
  27. Err(_) => SystemTime::now()
  28. .duration_since(UNIX_EPOCH)
  29. .expect("system clock before 1970-01-01")
  30. .as_secs(),
  31. }
  32. }
  34. fn format_iso8601_utc(epoch: u64) -> String {
  35. let secs_of_day = epoch % 86_400;
  36. let days = epoch / 86_400;
  37. let hour = secs_of_day / 3600;
  38. let minute = (secs_of_day % 3600) / 60;
  39. let second = secs_of_day % 60;
  41. let (year, month, day) = civil_from_days(days as i64);
  42. format!("{year:04}-{month:02}-{day:02}T{hour:02}:{minute:02}:{second:02}Z")
  43. }
  45. // Howard Hinnant's days-from-civil algorithm (public domain).
  46. // Input: days since 1970-01-01. Output: (year, month, day) on the proleptic Gregorian calendar.
  47. fn civil_from_days(z: i64) -> (i64, u32, u32) {
  48. let z = z + 719_468;
  49. let era = if z >= 0 { z } else { z - 146_096 } / 146_097;
  50. let doe = (z - era * 146_097) as u64;
  51. let yoe = (doe - doe / 1460 + doe / 36_524 - doe / 146_096) / 365;
  52. let y = yoe as i64 + era * 400;
  53. let doy = doe - (365 * yoe + yoe / 4 - yoe / 100);
  54. let mp = (5 * doy + 2) / 153;
  55. let d = (doy - (153 * mp + 2) / 5 + 1) as u32;
  56. let m = (if mp < 10 { mp + 3 } else { mp - 9 }) as u32;
  57. let year = y + i64::from(m <= 2);
  58. (year, m, d)
  59. }
  61. fn main() {
  62. let hash = git_short_hash();
  63. let timestamp = format_iso8601_utc(build_epoch());
  64. let target_os = env::var("CARGO_CFG_TARGET_OS").unwrap_or_else(|_| "unknown".to_string());
  65. let target_arch = env::var("CARGO_CFG_TARGET_ARCH").unwrap_or_else(|_| "unknown".to_string());
  67. let version_body = format!("{hash} — {target_os}/{target_arch} — built {timestamp}");
  69. println!("cargo:rustc-env=GIT_SHORT_HASH={hash}");
  70. println!("cargo:rustc-env=BUILD_TIMESTAMP={timestamp}");
  71. println!("cargo:rustc-env=VERSION_BODY={version_body}");
  73. println!("cargo:rerun-if-changed=.git/HEAD");
  74. println!("cargo:rerun-if-changed=.git/index");
  75. println!("cargo:rerun-if-env-changed=SOURCE_DATE_EPOCH");
  76. }

build.rs at commit c6528e5, under GPL-3.0 · at the source

Overview

Authors: William J. Nathan1, Chuanyuan Chen1,2, Rosy Sakr1,2, Bruno Siqueira Mietto3,4,2, Vincent van Batenburg5, Jeroen van den Berg5, Josette J. Wlaschin3, Ferenc Livak1, Elsa Callen1, Nancy Wong1, Eliza Y.H. Lloyd3, Hanna Silberberg3, Sushma Sharma6, Raj Chari7, Tzipporah Freeman8, Baek Kim8, Alexander van Oudenaarden5, Alexander T. Chesler9,10, Michael E. Ward11, Lisa D. Boxer1, Peter J. McHugh12, Andrei Chabes6, Claire E. Le Pichon3, André Nussenzweig1,13
ORCID iDs: Vincent van Batenburg, Lisa D. Boxer, André Nussenzweig
13 affiliations
  1. Laboratory of Genome Integrity, National Cancer Institute, NIH, Bethesda, MD 20892, USA
  2. These authors contributed equally
  3. Section on the Development of Neurodegeneration, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Bethesda, MD 20892, USA
  4. Institute of Biological Sciences, Federal University of Juiz de Fora, Juiz de Fora, 36036-900 MG, Brazil
  5. Oncode Institute, Hubrecht Institute-KNAW (Royal Netherlands Academy of Arts and Sciences) and University Medical Center Utrecht, 3584 CT Utrecht, the Netherlands
  6. Department of Medical Biochemistry and Biophysics, Umeå University, Umeå 90187, Sweden
  7. Genome Modification Core, Laboratory Animal Sciences Program, Frederick National Laboratory for Cancer Research, Frederick, MD 21701, USA
  8. Center for ViroScience and Cure, Department of Pediatrics, School of Medicine, Emory University, Atlanta, GA 30322, USA
  9. National Center for Complementary and Integrative Health, NIH, Bethesda, MD 20892, USA
  10. Present address: Research Management, Vertex Pharmaceuticals Incorporated, 50 Northern Avenue, Boston, MA 02210, USA
  11. National Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD 20892, USA
  12. Department of Oncology, MRC Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DS, UK
  13. Lead contact
Institutions: National Institutes of Health (United States); National Cancer Institute (United States); Universidade Federal de Juiz de Fora (Brazil); Eunice Kennedy Shriver National Institute of Child Health and Human Development (United States); Royal Netherlands Academy of Arts and Sciences (Netherlands); University Medical Center Utrecht (Netherlands); Oncode Institute (Netherlands); Umeå University (Sweden); Frederick National Laboratory for Cancer Research (United States); Emory University (United States); National Center for Complementary and Integrative Health (United States); National Institute of Neurological Disorders and Stroke (United States); John Radcliffe Hospital (United Kingdom); University of Oxford (United Kingdom); MRC Weatherall Institute of Molecular Medicine (United Kingdom)
Journal: Cell, volume 189, issue 13, pages 4005-4021.e11
Dates: published online 10 June 2026; in print 25 June 2026
Type: Research article · Language: English
License: CC BY-NC
Identifiers: DOI 10.1016/j.cell.2026.05.025 · PMID 42269607 · PMCID PMC13411057 · OpenAlex W7164126234
Open access: hybrid, a free copy (OpenAlex)
Status: code verified
Categories: human (organism), mouse (organism), other condition (population), cellular / molecular (subfield)
Keywords: DNA repair, Neuron, Nucleotide excision repair, Neurotoxicity, Cisplatin, Chemotherapy, Neuropathy, Deoxynucleotides
MeSH: Cisplatin*, DNA Repair*, Neurons*, Animals, Antineoplastic Agents, Cell Death, Deoxyribonucleotides, DNA Breaks, Double-Stranded, DNA Damage, Excision Repair, Humans, Mice (* major topic)
Topic: DNA Repair Mechanisms (Molecular Biology, Biochemistry, Genetics and Molecular Biology), according to OpenAlex
Funding: NIAID NIH HHS (R01 AI162633, R01 AI136581); Intramural NIH HHS (Z01 BC010959, ZIA BC010959, ZIA HD008966, Z99 CA999999, Z01 BC010283, ZIA BC010283); National Cancer Institute Division of Cancer Epidemiology and Genetics; NCI NIH HHS (HHSN261201500003I, HHSN261201500003C); NIH HHS (75N98022D00019)
Citations: cited by 4 papers (Europe PMC); 81 references in the paper
Research resources: anti-53BP1 RRID:AB_10001695, anti-CSB RRID:AB_10679889, IRDye 680RD goat anti-mouse IgG RRID:AB_10956588, Alexa Fluor 647 goat anti-rat RRID:AB_141778, Alexa Fluor 568 goat anti-rabbit RRID:AB_143157, anti-XPA RRID:AB_1925572, anti-RPA32 clone 4E4 RRID:AB_2238543, anti-ERCC1 (D-10) RRID:AB_2278023, Alexa Fluor 488 goat anti-mouse RRID:AB_2534088, Alexa Fluor 647 goat anti-rabbit RRID:AB_2535813, Alexa Fluor 647 chicken anti-mouse RRID:AB_2535869, anti-poly-ADP-ribose binding reagent RRID:AB_2665467, Alexa Fluor 647 anti-NeuN RRID:AB_2732785, anti-RRM2B (EPR8816) RRID:AB_2750599, anti-XPC (D1M5Y) RRID:AB_2798603, anti-phospho-histone H2AX clone JBW301 RRID:AB_309864, anti-β-tubulin RRID:AB_477579, IRDye 800CW goat anti-rabbit IgG RRID:AB_621843, anti-XPG RRID:AB_999684

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.

Reproduced under the paper's license (CC BY-NC), from the paper cited above.

Repository

Its files are read in the Code ↔ Paper reader above.

FelixKrueger/TrimGalore

License: GPL-3.0
State: the link answers, verified on 27 September 2026
Evidence: files inventoried
Commit: c6528e54512e0e388a392d36475291bcbf0eb0dd, 27 June 2026
Languages: Rust (24), TypeScript (2), Shell (2), Python (1)
Size: 267 files, 29 scripts
Software Heritage: not archived
Found in: the text, “Single-cell SAR-seq analysis”
Holds: README, license file, CITATION.cff, environment (Dockerfile), tests, continuous integration, documentation
Tools: Matplotlib (1 file), SAMtools (1 file)
Availability: 1 check, the latest on 27 September 2026: the link answers
  • 27 September 2026: the link answers
31 files
At the source: github.com/FelixKrueger/TrimGalore

The paper's code and data availability statement is in the Data section.

Tracing map

Proposed by the machine: these links were found in the paper and verified at the source, without human review. The map will receive a Zenodo DOI once one of the paper's authors has validated it with their ORCID.

What the map holds:

  • 1 repository of the authors' code, each at its verified commit, with its license and how the link was found in the paper;
  • 29 scripts, each with its path and the digest of its content;
  • no match between paragraphs and code yet;
  • neither the text of the paper nor the code itself.

Its JSON (tracing-map.json) is deposited on Zenodo with its DOI once the map is validated.

Data

No dataset and no data link were found in the paper.

Data and code availability

Microscopy data reported in this paper will be shared by the lead contact upon request.

This paper does not report original code.

All scSAR-seq, SAR-seq, END-seq, S1-END-seq, and RNA-seq datasets have been deposited at GEO (accession numbers GEO: GSE329935 and GEO: GSE329361) and are publicly available as of the date of publication.

Any additional information required to reanalyze the data reported in this paper is available from the lead contact upon request.

Reproduced under the paper's license (CC BY-NC), from the paper cited above.

Versions

The history of this record: each version stored by the harvester or made by a correction of its authors or of the maintainers of its code, and what changed in its facts. The texts of the paper (its abstract, its availability statements) are not part of it; versions that changed only those are not listed.

Version 2, 28 September 2026

  • Publisher: n/a → Cell Press
  • Authors: added André Nussenzweig (0000-0003-0037-7898); removed André Nussenzweig

Version 1, 27 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 24 authors, 8 keywords, 12 MeSH terms, 5 funders, 81 references, 19 RRIDs.

Cite

This paper

Nathan, W. J., Chen, C., Sakr, R., Mietto, B. S., van Batenburg, V., van den Berg, J., Wlaschin, J. J., Livak, F., Callen, E., Wong, N., Lloyd, E. Y., Silberberg, H., Sharma, S., Chari, R., Freeman, T., Kim, B., van Oudenaarden, A., Chesler, A. T., Ward, M. E., . . . Nussenzweig, A. (2026). DNA repair drives cisplatin-induced neuronal death. Cell, 189(13), 4005-4021.e11. https://doi.org/10.1016/j.cell.2026.05.025

BibTeX

@article{nathan2026dna,
author = {Nathan, William J. and Chen, Chuanyuan and Sakr, Rosy and Mietto, Bruno Siqueira and van Batenburg, Vincent and van den Berg, Jeroen and Wlaschin, Josette J. and Livak, Ferenc and Callen, Elsa and Wong, Nancy and Lloyd, Eliza Y.H. and Silberberg, Hanna and Sharma, Sushma and Chari, Raj and Freeman, Tzipporah and Kim, Baek and van Oudenaarden, Alexander and Chesler, Alexander T. and Ward, Michael E. and Boxer, Lisa D. and McHugh, Peter J. and Chabes, Andrei and Le Pichon, Claire E. and Nussenzweig, André},
title = {{DNA repair drives cisplatin-induced neuronal death}},
journal = {Cell},
year = {2026},
month = jun,
volume = {189},
number = {13},
pages = {4005--4021.e11},
publisher = {Cell Press},
issn = {0092-8674},
doi = {10.1016/j.cell.2026.05.025},
url = {https://doi.org/10.1016/j.cell.2026.05.025},
pmid = {42269607},
pmcid = {PMC13411057}
}

RIS

TY - JOUR
AU - Nathan, William J.
AU - Chen, Chuanyuan
AU - Sakr, Rosy
AU - Mietto, Bruno Siqueira
AU - van Batenburg, Vincent
AU - van den Berg, Jeroen
AU - Wlaschin, Josette J.
AU - Livak, Ferenc
AU - Callen, Elsa
AU - Wong, Nancy
AU - Lloyd, Eliza Y.H.
AU - Silberberg, Hanna
AU - Sharma, Sushma
AU - Chari, Raj
AU - Freeman, Tzipporah
AU - Kim, Baek
AU - van Oudenaarden, Alexander
AU - Chesler, Alexander T.
AU - Ward, Michael E.
AU - Boxer, Lisa D.
AU - McHugh, Peter J.
AU - Chabes, Andrei
AU - Le Pichon, Claire E.
AU - Nussenzweig, André
TI - DNA repair drives cisplatin-induced neuronal death
T2 - Cell
J2 - Cell
PY - 2026
DA - 2026/06/10
VL - 189
IS - 13
SP - 4005
EP - 4021.e11
SN - 0092-8674
PB - Cell Press
DO - 10.1016/j.cell.2026.05.025
UR - https://doi.org/10.1016/j.cell.2026.05.025
LA - en
ER -

CSL-JSON

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