Cre-dependent DNA recombination activates a STING-dependent innate immune response
| Autor: | Veit Hornung, Genevieve Pepin, Michael P. Gantier, Klara Höning, Jonathan Ferrand, Mark A. Behlke, Jason E. Cain, Daniel J. Gough, W. Samantha N. Jayasekara, Bryan R.G. Williams |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
DNA damage DNA repair Biology Cell Line law.invention Mice 03 medical and health sciences chemistry.chemical_compound Genome editing law Genetics Animals Humans Homologous Recombination Gene Innate immune system Integrases Nucleic Acid Enzymes Macrophages Membrane Proteins Epithelial Cells Fibroblasts Immunity Innate 3. Good health 030104 developmental biology chemistry Recombinant DNA Homologous recombination DNA |
| Zdroj: | Nucleic Acids Research ResearcherID |
| ISSN: | 1362-4962 0305-1048 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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