eccDNAs are apoptotic products with high innate immunostimulatory activity

Yuangao Wang, Meng Wang, Mohamed Nadhir Djekidel, Huan Chen, Di Liu, Frederick W. Alt and Yi Zhang ()
Additional contact information
Yuangao Wang: Howard Hughes Medical Institute
Meng Wang: Howard Hughes Medical Institute
Mohamed Nadhir Djekidel: Howard Hughes Medical Institute
Huan Chen: Howard Hughes Medical Institute
Di Liu: Harvard University
Frederick W. Alt: Howard Hughes Medical Institute
Yi Zhang: Howard Hughes Medical Institute

Nature, 2021, vol. 599, issue 7884, 308-314

Abstract: 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.

Date: 2021
References: Add references at CitEc
Citations: View citations in EconPapers (3)

Downloads: (external link)
https://www.nature.com/articles/s41586-021-04009-w Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:599:y:2021:i:7884:d:10.1038_s41586-021-04009-w

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/s41586-021-04009-w

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().