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Publication : Cre-dependent DNA recombination activates a STING-dependent innate immune response.

First Author  Pépin G Year  2016
Journal  Nucleic Acids Res Volume  44
Issue  11 Pages  5356-64
PubMed ID  27166376 Mgi Jnum  J:263632
Mgi Id  MGI:5924483 Doi  10.1093/nar/gkw405
Citation  Pepin G, et al. (2016) Cre-dependent DNA recombination activates a STING-dependent innate immune response. Nucleic Acids Res 44(11):5356-64
abstractText  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.
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