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bioRxiv · 10.1101/2020.05.28.119941

An anti-CRISPR protein induces strong non-specific DNA binding activity in a CRISPR-Cas complex

Lu, W.-T.·Trost, C. N.·Muller-Esparza, H.·Randau, L.·Davidson, A. R.
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Abstract

Phages and other mobile genetic elements express anti-CRISPR proteins (Acrs) to protect their genomes from destruction by CRISPR-Cas systems. Acrs usually block the ability of CRISPR-Cas systems to bind or cleave their nucleic acid substrates. Here, we investigate an unusual Acr, AcrIF9, that induces a gain-of-function to a type I-F CRISPR-Cas (Csy) complex, causing it to bind strongly to DNA that lacks both a PAM sequence and sequence complementarity. We show that specific and non-specific dsDNA compete for the same site on the Csy:AcrIF9 complex with rapid exchange, but specific ssDNA appears to still bind through complemetarity to the CRISPR RNA. We also demonstrate that induction of non-specific DNA-binding is a conserved property of diverse AcrIF9 homologues, implying that this activity contributes the biologically relevant function of this Acr family. AcrIF9 provides another example of the surprising variety of mechanisms by which Acrs inhibit CRISPR-Cas systems.

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Lu, W.-T., Trost, C. N., Muller-Esparza, H., Randau, L., Davidson, A. R.. 2020-05-29. An anti-CRISPR protein induces strong non-specific DNA binding activity in a CRISPR-Cas complex. https://doi.org/10.1101/2020.05.28.119941

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