Figure 7.

Schematic diagram showing the repressor roles of Aca1 and Aca2 and their potential value in genome editing.A, in prophage or late infection stage of phage, the accumulated Aca1 or Aca2 proteins can function as repressor through binding to the inverted repeat (IR) in the promoter of the acr-aca operon, which then alleviates the deleterious effects on phages caused by the strong and constitutive transcription from the promoter of the operon. We have presented the structural basis for Aca1-and Aca2-mediating anti-CRISPR repression. B, a prophage within a bacterial host may have inhibitory effects on genome editing in the bacterial host, as inhibited by Acr proteins produced from the prophage. The epitopic expression of the Aca1 or Aca2 proteins can potentially repress the transcription from the acr promoter, which thus releases the inhibitory effects of the Acr proteins on CRISPR-Cas-mediated genome editing in the host, as proved by Csörgő et al. (29). Our structures can be used as a template/start to design stronger Aca1 and Aca2 repressors (higher binding affinity to the target DNA), which would potentially provide a more powerful anti-anti-CRISPR mechanism for different applications including genome editing.