Structural biology of CRISPR–Cas immunity and genome editing enzymes

• Published in: Nature reviews. Microbiology Vol. 20; no. 11; pp. 641 - 656
• Main Authors: Wang, Joy Y., Pausch, Patrick, Doudna, Jennifer A.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.11.2022; Nature Publishing Group
• Subjects: 631/326/4041; 631/45/147; 631/45/500; 631/535; 631/61; Antitoxins; Antitoxins - genetics; Bacteria; Biological evolution; Biology; Biomedical and Life Sciences; Biotechnology; CRISPR; CRISPR-Cas Systems - genetics; DNA Transposable Elements; Editing; Enzymes; Evolution; Gene Editing; Genome editing; Genomes; Immune system; Immunity; Infectious Diseases; Life Sciences; Medical Microbiology; Microbiology; Molecular modelling; Molecular structure; Parasitology; Retroelements; Review Article; Ribonucleic acid; RNA; RNA, Bacterial; Toxins; Transposons; Virology
• ISSN: 1740-1526; 1740-1534
• DOI: 10.1038/s41579-022-00739-4

CRISPR–Cas systems provide resistance against foreign mobile genetic elements and have a wide range of genome editing and biotechnological applications. In this Review, we examine recent advances in understanding the molecular structures and mechanisms of enzymes comprising bacterial RNA-guided CRISPR–Cas immune systems and deployed for wide-ranging genome editing applications. We explore the adaptive and interference aspects of CRISPR–Cas function as well as open questions about the molecular mechanisms responsible for genome targeting. These structural insights reflect close evolutionary links between CRISPR–Cas systems and mobile genetic elements, including the origins and evolution of CRISPR–Cas systems from DNA transposons, retrotransposons and toxin–antitoxin modules. We discuss how the evolution and structural diversity of CRISPR–Cas systems explain their functional complexity and utility as genome editing tools. CRISPR–Cas systems provide resistance against foreign mobile genetic elements and have a wide range of genome editing and biotechnological applications. In this Review, Wang, Pausch and Doudna examine recent advances in understanding the molecular structures and mechanisms of enzymes comprising bacterial RNA-guided CRISPR–Cas immune systems and deployed for wide-ranging genome editing applications.