{
  "abstract": "The innate immune system maintains cellular homeostasis by recognizing cytosolic nucleic acids. While the cGAS-STING pathway is well characterized in detecting non-self-DNA, its response to self-DNA originating from the host nucleus remains unclear. Extrachromosomal circular DNA (eccDNA), a form of self-DNA often enriched in cancer, has been implicated in immune modulation, yet its ability to activate cGAS-STING remains unresolved. Here, we developed a Cre-loxP-based eccDNA reporter system, where Cre-mediated eccDNA formation triggers expression of the fluorescent protein mCitrine, enabling time-resolved, single-cell analysis of chromosome-derived eccDNA dynamics and STING activation. Using an mRuby3-STING reporter, we found that low-dose plasmid transfection induced STING activation, as evidenced by modest STING accumulation and downstream cytokine induction. Cells carrying chromosome-derived cytosolic eccDNA also showed a modest, cGAS-dependent accumulation of STING. However, this accumulation was uncoupled from detectable STING-Ser366 phosphorylation or induction of downstream cytokines. These findings indicate that chromosome-derived eccDNA does not drive detectable STING signaling under the conditions tested, and that STING accumulation and its activation are mechanistically separable steps. This work provides a foundation for understanding the immunological roles of eccDNA in genome instability and cancer.",
  "abstract_shown": true,
  "affiliations": [
    "Kyoto University"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 3,
  "authors": [
    {
      "name": "H. Dushimyineza"
    },
    {
      "name": "J. Cai"
    },
    {
      "affs": [
        0
      ],
      "name": "M. T. Hayashi"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/d08pq7kpxk9my.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.10.23.761201",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.10.23.761201v1.full",
  "id": "d08pq7kpxk9my",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.10.23.761201v1",
  "language": null,
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "cell biology"
    ],
    [
      "openalex",
      "2403|interferon and immune responses"
    ]
  ],
  "openalex": "W7223578320",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.10.23.761201v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-23",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/d08pq7kpxk9my.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:29:37Z",
      "native_id": "10.64898/2026.10.23.761201",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.10.23.761201v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:cell biology",
      "subfield": "cell-biology"
    }
  ],
  "title": "Uncoupling of STING Accumulation and Activation upon Chromosome-Derived Extrachromosomal Circular DNA Formation",
  "title_text": "Uncoupling of STING Accumulation and Activation upon Chromosome-Derived Extrachromosomal Circular DNA Formation",
  "type": "preprint",
  "updated_at": "2026-10-30T12:29:37Z",
  "url": "https://research.draconitic.com/paper/d08pq7kpxk9my",
  "venue": "bioRxiv",
  "versions": []
}