CRISPR-associated Cas12 proteins are a highly variable collection of nucleic acid-targeting proteins. All Cas12 variants use RNA guides and a single nuclease domain to target complementary DNA or, in rare cases, RNA.
The high variability of Cas12 effectors can be explained by a series of independent evolution events from different transposon-associated TnpB-like ancestors. Despite basic structural and functional similarities, this has resulted in unprecedented variation of the Cas12 effector proteins in terms of size, domain composition, guide structure, target identity and interference strategy. In this Review, we compare the unique molecular features of natural and engineered Cas12 and TnpB variants.
–Cas enzymes in cancer therapeutics and detection.Kersulyte, D., Mukhopadhyay, A. K., Shirai, M., Nakazawa, T. & Berg, D. E. Functional organization and insertion specificity of IS607, a chimeric element ofAravind, L., Makarova, K. S. & Koonin, E. V. Holliday junction resolvases and related nucleases: identification of new families, phyletic distribution and evolutionary trajectories. Ch. 2 .Swarts, D. C., van der Oost, J. & Jinek, M.
RNA.Zhang, H., Li, Z., Xiao, R. & Chang, L. Mechanisms for target recognition and cleavage by the Cas12i RNA-guided endonuclease.Gao, P., Yang, H., Rajashankar, K. R., Huang, Z. & Patel, D. J. Type V editing with a hypercompact Cas12f1 and engineered guide RNAs delivered by adeno-associated virus.Chen, W. et al. Cas12n nucleases, early evolutionary intermediates of type V
-associated nucleases.Kim, Y. B. et al. A novel mechanistic framework for precise sequence replacement using reverse transcriptase and diverse
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