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Stimulation of Cytoplasmic DNA Sensing Pathways In Vitro and In Vivo
Published on: September 18, 2014
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Cre-dependent DNA recombination activates a STING-dependent innate immune response
Geneviève Pépin1, Jonathan Ferrand1, Klara Höning2
1Centre 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.
Nucleic Acids Research
|May 12, 2016
Summary
Cre recombinase triggers an antiviral response in cells by activating the STING pathway, independent of DNA recombination. Lowering cell density can mitigate this effect, impacting gene editing research.
Area of Science:
- Molecular Biology
- Immunology
- Genetics
Background:
- Gene-recombinase technologies like Cre/loxP are crucial for studying gene function.
- These technologies can cause DNA damage, leading to potential side effects.
- The cellular response to such DNA damage is not fully understood.
Purpose of the Study:
- To investigate the cellular response to Cre-mediated DNA recombination.
- To determine if Cre activity, independent of loxP recombination, triggers specific cellular pathways.
- To explore potential strategies for mitigating unintended cellular responses in gene-editing applications.
Main Methods:
- Utilized Cre/loxP-mediated DNA recombination in mammalian cells.
- Assessed the activation of the cytosolic DNA sensor STING.
- Monitored DNA damage and cytoplasmic DNA accumulation.
- Investigated the role of cell density in modulating the cellular response.
Main Results:
- Cre recombinase induces a robust antiviral response in mammalian cells, independent of legitimate loxP recombination.
- This response is mediated by the recruitment of STING, linked to Cre-dependent DNA damage and cytoplasmic DNA.
- The antiviral response is influenced by cell-cell interactions, with low cell densities mitigating the effects.
- The STING pathway activation has broad implications for various research fields.
Conclusions:
- Cre-mediated DNA recombination activates a STING-dependent antiviral response, presenting a significant side effect.
- Understanding this interplay is crucial for interpreting results in gene-editing studies.
- Manipulating cell density offers a potential method to reduce Cre-induced cellular stress.
- These findings have wide-ranging implications for immunology, cancer biology, metabolism, and stem cell research.
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