A-to-Z interactions in fear extinction

The functional importance of Z-DNA — a left-turning helical conformation of DNA — is unclear. Marshall et al. identified an immediate increase in the formation of Z-DNA in neurons in the prefrontal cortex (PFC) of mice that had undergone fear learning. Subsequent fear extinction training led to increases in the levels of the Z-DNA-binding protein ADAR1 in activated PFC neurons, where it bound to more than 100 Z-DNA loci and promoted RNA editing. ADAR1–Z-DNA binding reduced Z-DNA levels, and knock-down of Adar1 disrupted fear extinction learning, suggesting the interaction between Z-DNA and ADAR1 is necessary for memory flexibility.


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  1. Marshall, P. R. et al. Dynamic regulation of Z-DNA in the mouse prefrontal cortex by the RNA-editing enzyme Adar1 is required for fear extinction. Nat. Neurosci. https://doi.org/10.1038/s41593-020-0627-5 (2020)

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Correspondence to Natasha Bray.

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Bray, N. A-to-Z interactions in fear extinction. Nat Rev Neurosci 21, 351 (2020). https://doi.org/10.1038/s41583-020-0321-3

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