CRISPR-Associated Primase-Polymerases are implicated in prokaryotic CRISPR-Cas adaptation

Abstract CRISPR-Cas pathways provide prokaryotes with acquired “immunity” against foreign genetic elements, including phages and plasmids. Although many of the proteins associated mechanisms are characterized, some requisite enzymes remain elusive. Genetic studies have implicated host DNA polymerases in systems but CRISPR-specific replicases not yet been discovered. We identified characterised a family CRISPR-Associated Primase-Polymerases (CAPPs) range that operonically Cas1 Cas2. CAPPs belong to Primase-Polymerase (Prim-Pol) superfamily operate various repair replication maintain genome stability. Here, we characterise synthesis activities bacterial CAPP homologues from Type IIIA IIIB establish they possess replicase priming, polymerisation strand-displacement. demonstrate operonically-associated partners, Cas2, form complex possesses spacer integration activity. show physically associate Cas bespoke complexes. Finally, propose how activities, conjunction their may function undertake key roles adaptation.