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Anti-CRISPR-Associated Proteins Are Crucial Repressors of Anti-CRISPR Transcription.


ABSTRACT: Phages express anti-CRISPR (Acr) proteins to inhibit CRISPR-Cas systems that would otherwise destroy their genomes. Most acr genes are located adjacent to anti-CRISPR-associated (aca) genes, which encode proteins with a helix-turn-helix DNA-binding motif. The conservation of aca genes has served as a signpost for the identification of acr genes, but the function of the proteins encoded by these genes has not been investigated. Here we reveal that an acr-associated promoter drives high levels of acr transcription immediately after phage DNA injection and that Aca proteins subsequently repress this transcription. Without Aca activity, this strong transcription is lethal to a phage. Our results demonstrate how sufficient levels of Acr proteins accumulate early in the infection process to inhibit existing CRISPR-Cas complexes in the host cell. They also imply that the conserved role of Aca proteins is to mitigate the deleterious effects of strong constitutive transcription from acr promoters.

SUBMITTER: Stanley SY 

PROVIDER: S-EPMC6754177 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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Anti-CRISPR-Associated Proteins Are Crucial Repressors of Anti-CRISPR Transcription.

Stanley Sabrina Y SY   Borges Adair L AL   Chen Kuei-Ho KH   Swaney Danielle L DL   Krogan Nevan J NJ   Bondy-Denomy Joseph J   Davidson Alan R AR  

Cell 20190829 6


Phages express anti-CRISPR (Acr) proteins to inhibit CRISPR-Cas systems that would otherwise destroy their genomes. Most acr genes are located adjacent to anti-CRISPR-associated (aca) genes, which encode proteins with a helix-turn-helix DNA-binding motif. The conservation of aca genes has served as a signpost for the identification of acr genes, but the function of the proteins encoded by these genes has not been investigated. Here we reveal that an acr-associated promoter drives high levels of  ...[more]

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