Cre-dependent DNA recombination activates a STING-dependent innate immune response

Geneviève Pépin, Jonathan Ferrand, Klara Höning, W. Samantha N Jayasekara, Jason E. Cain, Mark A. Behlke, Daniel J. Gough, Bryan R G Williams, Veit Hornung, Michael P. Gantier

Research output: Contribution to journalArticleResearchpeer-review

16 Citations (Scopus)

Abstract

Gene-recombinase technologies, such as Cre/loxP-mediated DNA recombination, are important tools in the study of gene function, but have potential side effects due to damaging activity on DNA. Here we show that DNA recombination by Cre instigates a robust antiviral response in mammalian cells, independent of legitimate loxP recombination. This is due to the recruitment of the cytosolic DNA sensor STING, concurrent with Cre-dependent DNA damage and the accumulation of cytoplasmic DNA. Importantly, we establish a direct interplay between this antiviral response and cell-cell interactions, indicating that low cell densities in vitro could be useful to help mitigate these effects of Cre. Taking into account the wide range of interferon stimulated genes that may be induced by the STING pathway, these results have broad implications in fields such as immunology, cancer biology, metabolism and stem cell research. Further, this study sets a precedent in the field of gene-engineering, possibly applicable to other enzymatic-based genome editing technologies.
Original languageEnglish
Pages (from-to)5356-5364
Number of pages9
JournalNucleic Acids Research
Volume44
Issue number11
DOIs
Publication statusPublished - 20 Jun 2016

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