IDEAS home Printed from https://ideas.repec.org/a/nat/nature/v599y2021i7884d10.1038_s41586-021-04009-w.html
   My bibliography  Save this article

eccDNAs are apoptotic products with high innate immunostimulatory activity

Author

Listed:
  • Yuangao Wang

    (Howard Hughes Medical Institute
    Boston Children’s Hospital)

  • Meng Wang

    (Howard Hughes Medical Institute
    Boston Children’s Hospital)

  • Mohamed Nadhir Djekidel

    (Howard Hughes Medical Institute
    Boston Children’s Hospital)

  • Huan Chen

    (Howard Hughes Medical Institute
    Boston Children’s Hospital)

  • Di Liu

    (Harvard University
    Harvard Medical School)

  • Frederick W. Alt

    (Howard Hughes Medical Institute
    Boston Children’s Hospital
    Harvard University)

  • Yi Zhang

    (Howard Hughes Medical Institute
    Boston Children’s Hospital
    Harvard University
    Harvard Stem Cell Institute WAB-149G)

Abstract

Extrachromosomal circular DNA elements (eccDNAs) have been described in the literature for several decades, and are known for their broad existence across different species1,2. However, their biogenesis and functions are largely unknown. By developing a new circular DNA enrichment method, here we purified and sequenced full-length eccDNAs with Nanopore sequencing. We found that eccDNAs map across the entire genome in a close to random manner, suggesting a biogenesis mechanism of random ligation of genomic DNA fragments. Consistent with this idea, we found that apoptosis inducers can increase eccDNA generation, which is dependent on apoptotic DNA fragmentation followed by ligation by DNA ligase 3. Importantly, we demonstrated that eccDNAs can function as potent innate immunostimulants in a manner that is independent of eccDNA sequence but dependent on eccDNA circularity and the cytosolic DNA sensor Sting. Collectively, our study not only revealed the origin, biogenesis and immunostimulant function of eccDNAs but also uncovered their sensing pathway and potential clinical implications in immune response.

Suggested Citation

  • Yuangao Wang & Meng Wang & Mohamed Nadhir Djekidel & Huan Chen & Di Liu & Frederick W. Alt & Yi Zhang, 2021. "eccDNAs are apoptotic products with high innate immunostimulatory activity," Nature, Nature, vol. 599(7884), pages 308-314, November.
    • Handle: RePEc:nat:nature:v:599:y:2021:i:7884:d:10.1038_s41586-021-04009-w
    DOI: 10.1038/s41586-021-04009-w
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41586-021-04009-w
    File Function: Abstract
    Download Restriction: Access to the full text of the articles in this series is restricted.
    File URL: https://libkey.io/10.1038/s41586-021-04009-w?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    As the access to this document is restricted, you may want to search for a different version of it.

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Jinxin Phaedo Chen & Constantin Diekmann & Honggui Wu & Chong Chen & Giulia Chiara & Enrico Berrino & Konstantinos L. Georgiadis & Britta A. M. Bouwman & Mohit Virdi & Luuk Harbers & Sara Erika Bellom, 2024. "scCircle-seq unveils the diversity and complexity of extrachromosomal circular DNAs in single cells," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    2. Panpan Zhang & Assane Mbodj & Abirami Soundiramourtty & Christel Llauro & Alain Ghesquière & Mathieu Ingouff & R. Keith Slotkin & Frédéric Pontvianne & Marco Catoni & Marie Mirouze, 2023. "Extrachromosomal circular DNA and structural variants highlight genome instability in Arabidopsis epigenetic mutants," Nature Communications, Nature, vol. 14(1), pages 1-11, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:nature:v:599:y:2021:i:7884:d:10.1038_s41586-021-04009-w. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.