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Bacterial Cas12i crRNA R-loop complex before target DNA cleavage (PDB id: 7EU9; Zhang B, Luo D, Li Y, Perculija V, Chen J, Lin J, Ye Y, Ouyang S. 2021. Mechanistic insights into the R-loop formation and cleavage in CRISPR-Cas12i1. Nat Commun 12: 3476). Cas12i is a newly identified member of the functionally diverse type V CRISPR-Cas effectors, shown here in a pre-cleavage crRNA–DNA complex. Formation of the RNA–DNA heteroduplex triggers a conformational rearrangement that unleashes DNase activity. The RNA backbone is displayed as a red ribbon; DNA backbones are displayed as orange ribbons; block bases use NDB colors: A—red, C—yellow, G—green, T—blue, U—cyan; protein is displayed as a gold ribbon. Cover image provided by the Nucleic Acid Database (ndbserver.rutgers.edu). Image generated using DSSR and PyMOL (Lu XJ. 2020. Nucleic Acids Res 48: e74).