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CRISPR-Cas systems are transformative tools for gene editing which can be tuned or controlled by anti-CRISPRs (Acrs) - phage derived inhibitors that regulate CRISPR-Cas activity. However, Acrs that ar...

Yuan and colleagues reveal that type II CRISPR-Cas systems dominate the human gut, and diverse gut phage-encoded anti-CRISPR (Acr) proteins target these systems. They identify a widespread family, Gut...

If you’ve just started learning about accessibility, you might be a bit overwhelmed by all the jargon. WCAG, VPAT, s508, Level A – what on earth are they? Do they…

Anti-CRISPRs (Acrs) are diverse proteins or RNAs that protect invading phages and plasmids from host CRISPR-Cas immunity. Most Acrs neutralize their cognate Cas proteins via direct physical interaction. Here we describe CasPRs, a particularly widespread family of DNA-binding Acrs that recognize specific sequence motifs within cas gene coding regions, thereby blocking RNA polymerase and silencing transcription. We demonstrate that eight diverse CasPRs bind to the cas8b gene to repress the type I-B CRISPR-Cas system in its native host, Listeria seeligeri . Meanwhile, a CasPR from Streptococcus dysgalactiae silences type II-A CRISPR-Cas immunity by binding to the cas9 coding sequence. We found that one CasPR is required to inhibit CRISPR immunity during lysogeny by its host prophage. Taken together, our results indicate that members of the CasPR family have diverged to silence completely unrelated CRISPR types, and suggest transcriptional repression is a common mode of phage-mediated immune antagonism. ### Competing Interest Statement AJM is a co-founder and advisor of Profluent Bio. The other author declares no competing interests. National Institute of General Medical Sciences, https://ror.org/04q48ey07, R35GM142460, GM136534 U.S. National Science Foundation, FAIN2235762 Defense Advanced Research Projects Agency, https://ror.org/02caytj08, HR00112590142 Rita Allen Foundation, https://ror.org/0515k5w36