Format

Send to

Choose Destination
Nucleic Acids Res. 2016 Jun 20;44(11):5356-64. doi: 10.1093/nar/gkw405. Epub 2016 May 10.

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

Author information

1
Centre for Innate Immunity and Infectious Diseases, Hudson Institute of Medical Research, Clayton, Victoria 3168, Australia Department of Molecular and Translational Science, Monash University, Clayton, Victoria 3168, Australia.
2
Institute of Molecular Medicine, University Hospital University of Bonn, 53127 Bonn, Germany.
3
Department of Molecular and Translational Science, Monash University, Clayton, Victoria 3168, Australia Centre for Cancer Research, Hudson Institute of Medical Research, Clayton, Victoria 3168, Australia.
4
Integrated DNA Technologies Inc., Coralville, IA 52241, USA.
5
Institute of Molecular Medicine, University Hospital University of Bonn, 53127 Bonn, Germany Gene Centre and Department of Biochemistry, Ludwig-Maximilians-University Munich, 81377 Munich, Germany.
6
Centre for Innate Immunity and Infectious Diseases, Hudson Institute of Medical Research, Clayton, Victoria 3168, Australia Department of Molecular and Translational Science, Monash University, Clayton, Victoria 3168, Australia michael.gantier@hudson.org.au.

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.

PMID:
27166376
PMCID:
PMC4914124
DOI:
10.1093/nar/gkw405
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Silverchair Information Systems Icon for PubMed Central
Loading ...
Support Center