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Updated: Mar 13, 2026

Detection and Visualization of DNA Damage-induced Protein Complexes in Suspension Cell Cultures Using the Proximity Ligation Assay
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Interferon stimulatory DNA activates the DNA damage signaling through ATM and DNA-PK sensing

Samira Kemiha1, Lorena Rejón-Franco1, Estelle Ghibaudo1

  • 1Université Côte d'Azur, IRCAN, CNRS, INSERM, Nice, France.

The Journal of Biological Chemistry
|March 11, 2026
PubMed

Insights

Foreign DNA, like Interferon Stimulatory DNA (ISD), triggers both innate immune responses and DNA damage signaling in cells. This study reveals ISD activates DNA damage sensors ATM and DNA-PK, independent of the cGAS-STING pathway.

Area of Science:

  • Cellular Biology
  • Immunology
  • Genetics

Background:

  • Cytoplasmic DNA in eukaryotic cells signals danger, activating innate immunity.
  • The cGAS-STING pathway detects cytoplasmic double-stranded DNA (dsDNA), inducing type I Interferon (IFN-I) and inflammation.
  • Interferon Stimulatory DNA (ISD) is a linear dsDNA tool for studying cGAS-STING.

Purpose of the Study:

  • To investigate whether ISD stimulates DNA damage signaling pathways.
  • To determine if ISD activates DNA damage sensor kinases.
  • To elucidate the relationship between ISD, cGAS-STING, and DNA damage response.

Main Methods:

  • Treatment of mammalian cells with ISD.
  • Analysis of cGAS-STING pathway activation.
  • Assessment of ATM and DNA-PK kinase activation using specific assays.

Main Results:

  • ISD was found to stimulate DNA damage signaling.
  • ISD activated both ATM and DNA-PK kinases.
  • This activation occurred independently of the cGAS-STING pathway.

Conclusions:

  • Foreign DNA, such as ISD, can initiate DNA damage responses.
  • The DNA damage response can be triggered by non-genomic DNA lesions.
  • ISD links innate immunity and DNA damage checkpoints, coordinating cellular protective functions.
Keywords:
ATMDNA damage responseDNA-PKInterferon stimulatory DNAcGAS-STING pathway

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