CasX enzymes comprise a distinct family of RNA-guided genome editors
| Autor: | Liu, Jun-Jie, Orlova, Natalia, Oakes, Benjamin L, Ma, Enbo, Spinner, Hannah B, Baney, Katherine LM, Chuck, Jonathan, Tan, Dan, Knott, Gavin J, Harrington, Lucas B, Al-Shayeb, Basem, Wagner, Alexander, Brötzmann, Julian, Staahl, Brett T, Taylor, Kian L, Desmarais, John, Nogales, Eva, Doudna, Jennifer A |
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| Rok vydání: | 2019 |
| Předmět: |
Evolution
General Science & Technology 1.1 Normal biological development and functioning CRISPR-Associated Proteins Protein Domains Models Underpinning research MD Multidisciplinary Escherichia coli Genetics Humans Gene Silencing DNA Cleavage Kinetoplastida Gene Editing Genome Cryoelectron Microscopy Human Genome Bacterial Molecular DNA Emerging Infectious Diseases Infectious Diseases Nucleic Acid Conformation RNA Generic health relevance CRISPR-Cas Systems Guide Human Biotechnology |
| Zdroj: | Nature, vol 566, iss 7743 Liu, Jun-Jie; Orlova, Natalia; Oakes, Benjamin L; Ma, Enbo; Spinner, Hannah B; Baney, Katherine LM; et al.(2019). CasX enzymes comprise a distinct family of RNA-guided genome editors.. Nature, 566(7743), 218-223. doi: 10.1038/s41586-019-0908-x. UC Berkeley: Retrieved from: http://www.escholarship.org/uc/item/86h3d967 |
| DOI: | 10.1038/s41586-019-0908-x. |
| Popis: | The RNA-guided CRISPR-associated (Cas) proteins Cas9 and Cas12a provide adaptive immunity against invading nucleic acids, and function as powerful tools for genome editing in a wide range of organisms. Here we reveal the underlying mechanisms of a third, fundamentally distinct RNA-guided genome-editing platform named CRISPR-CasX, which uses unique structures for programmable double-stranded DNAbinding and cleavage. Biochemical and in vivo data demonstrate that CasX is active for Escherichia coli and human genome modification. Eight cryo-electron microscopy structures of CasX in different states of assembly with its guide RNA and double-stranded DNA substrates reveal an extensive RNA scaffold and a domain required for DNA unwinding. These data demonstrate how CasX activity arose through convergent evolution to establish an enzyme family that is functionally separate from both Cas9 and Cas12a. |
| Databáze: | OpenAIRE |
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