Evidence map›Paper›PMID 34001856›Full record

ArticleCell death discovery2021

ROS induces NETosis by oxidizing DNA and initiating DNA repair.

Dhia Azzouz, Meraj A Khan, Nades Palaniyar

Open access · goldAbstract read
In one paragraph

Article in Cell death discovery, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 118 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
118citing papers in PubMed, 1 pooled it
9.3field-weighted citation impact, top 1% 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

118 citing papers in PubMed, 1 synthesis or guideline pooled it, 182 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Review
  4. Article
  5. Immunomodulatory Nanozymes as Programmable Redox-Immune Set-Point Regulators.Small (Weinheim an der Bergstrasse, Germany) · 2026
    Review
  6. Article
  7. Detection ofInternational journal of molecular sciences · 2026
    Article
  8. Article
  9. Article
  10. Article
  11. Review
  12. Review
  13. Macrophage Extracellular Traps in Immunity and Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Review
  14. Review
  15. Review
  16. Article
  17. Article
  18. Article
  19. Review
  20. Article

58 more citing papers are in PubMed but not listed here.

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

3 authors at 2 institutions in 1 country.

Dhia AzzouzProgram in Translational Medicine, Peter Gilgan Centre for Research and Learning, The Hospital for Sick Children, Toronto, ON, Canada.
Meraj A KhanProgram in Translational Medicine, Peter Gilgan Centre for Research and Learning, The Hospital for Sick Children, Toronto, ON, Canada.
Nades PalaniyarProgram in Translational Medicine, Peter Gilgan Centre for Research and Learning, The Hospital for Sick Children, Toronto, ON, Canada. nades.palaniyar@sickkids.ca.
University of Toronto · CAHospital for Sick Children · CA

Funding

Cystic Fibrosis Canada (Fibrose kystique Canada) 3180Gouvernement du Canada | Canadian Institutes of Health Research (Instituts de Recherche en Santé du Canada) MOP-111012Gouvernement du Canada | Natural Sciences and Engineering Research Council of Canada (Conseil de Recherches en Sciences Naturelles et en Génie du Canada) RGPIN436250-13
6 · The paper itself

Abstract

Reactive oxygen species (ROS) are essential for neutrophil extracellular trap (NET) formation or NETosis. Nevertheless, how ROS induces NETosis is unknown. Neutrophil activation induces excess ROS production and a meaningless genome-wide transcription to facilitate chromatin decondensation. Here we show that the induction of NADPH oxidase-dependent NETosis leads to extensive DNA damage, and the subsequent translocation of proliferating cell nuclear antigen (PCNA), a key DNA repair protein, stored in the cytoplasm into the nucleus. During the activation of NETosis (e.g., by phorbol myristate acetate, Escherichia coli LPS, Staphylococcus aureus (RN4220), or Pseudomonas aeruginosa), preventing the DNA-repair-complex assembly leading to nick formation that decondenses chromatin causes the suppression of NETosis (e.g., by inhibitors to, or knockdown of, Apurinic endonuclease APE1, poly ADP ribose polymerase PARP, and DNA ligase). The remaining repair steps involving polymerase activity and PCNA interactions with DNA polymerases β/δ do not suppress agonist-induced NETosis. Therefore, excess ROS produced during neutrophil activation induces NETosis by inducing extensive DNA damage (e.g., oxidising guanine to 8-oxoguanine), and the subsequent DNA repair pathway, leading to chromatin decondensation.

Identifiers

PMID34001856
PMCPMC8128883
OpenAlexW3163218484

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.