Structural biology of CRISPR-Cas immunity and genome editing enzymes

Joy Y Wang^{1

2}, Patrick Pausch³, Jennifer A Doudna^{4

5

6

7

8

9

10

11}

Affiliations

¹ Department of Chemistry, University of California, Berkeley, Berkeley, CA, USA.
² Innovative Genomics Institute, University of California, Berkeley, Berkeley, CA, USA.
³ VU LSC-EMBL Partnership for Genome Editing Technologies, Life Sciences Center, Vilnius University, Vilnius, Lithuania. patrick.pausch@gmc.vu.lt.
⁴ Department of Chemistry, University of California, Berkeley, Berkeley, CA, USA. doudna@berkeley.edu.
⁵ Innovative Genomics Institute, University of California, Berkeley, Berkeley, CA, USA. doudna@berkeley.edu.
⁶ Howard Hughes Medical Institute, University of California, Berkeley, Berkeley, CA, USA. doudna@berkeley.edu.
⁷ Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA, USA. doudna@berkeley.edu.
⁸ California Institute for Quantitative Biosciences (QB3), University of California, Berkeley, Berkeley, CA, USA. doudna@berkeley.edu.
⁹ MBIB Division, Lawrence Berkeley National Laboratory, Berkeley, CA, USA. doudna@berkeley.edu.
¹⁰ Gladstone Institutes, University of California, San Francisco, San Francisco, CA, USA. doudna@berkeley.edu.
¹¹ Gladstone-UCSF Institute of Genomic Immunology, San Francisco, CA, USA. doudna@berkeley.edu.

PMID: 35562427
DOI: 10.1038/s41579-022-00739-4

Review

Structural biology of CRISPR-Cas immunity and genome editing enzymes

Joy Y Wang et al. Nat Rev Microbiol. 2022 Nov.

. 2022 Nov;20(11):641-656.

doi: 10.1038/s41579-022-00739-4. Epub 2022 May 13.

Authors

Joy Y Wang^{1

2}, Patrick Pausch³, Jennifer A Doudna^{4

5

6

7

8

9

10

11}

Affiliations

¹ Department of Chemistry, University of California, Berkeley, Berkeley, CA, USA.
² Innovative Genomics Institute, University of California, Berkeley, Berkeley, CA, USA.
³ VU LSC-EMBL Partnership for Genome Editing Technologies, Life Sciences Center, Vilnius University, Vilnius, Lithuania. patrick.pausch@gmc.vu.lt.
⁴ Department of Chemistry, University of California, Berkeley, Berkeley, CA, USA. doudna@berkeley.edu.
⁵ Innovative Genomics Institute, University of California, Berkeley, Berkeley, CA, USA. doudna@berkeley.edu.
⁶ Howard Hughes Medical Institute, University of California, Berkeley, Berkeley, CA, USA. doudna@berkeley.edu.
⁷ Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA, USA. doudna@berkeley.edu.
⁸ California Institute for Quantitative Biosciences (QB3), University of California, Berkeley, Berkeley, CA, USA. doudna@berkeley.edu.
⁹ MBIB Division, Lawrence Berkeley National Laboratory, Berkeley, CA, USA. doudna@berkeley.edu.
¹⁰ Gladstone Institutes, University of California, San Francisco, San Francisco, CA, USA. doudna@berkeley.edu.
¹¹ Gladstone-UCSF Institute of Genomic Immunology, San Francisco, CA, USA. doudna@berkeley.edu.

PMID: 35562427
DOI: 10.1038/s41579-022-00739-4

Abstract

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.

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References

1. Barrangou, R. et al. CRISPR provides acquired resistance against viruses in prokaryotes. Science 315, 1709–1712 (2007). - PubMed - DOI
1. Knott, G. J. & Doudna, J. A. CRISPR-Cas guides the future of genetic engineering. Science 361, 866–869 (2018). - PubMed - PMC - DOI
1. Koonin, E. V. & Makarova, K. S. Origins and evolution of CRISPR-Cas systems. Phil. Trans. R. Soc. B 374, 20180087 (2019). - PubMed - PMC - DOI
1. Hille, F. et al. The biology of CRISPR-Cas: backward and forward. Cell 172, 1239–1259 (2018). - PubMed - DOI
1. Shmakov, S. et al. Discovery and functional characterization of diverse class 2 CRISPR-Cas systems. Mol. Cell 60, 385–397 (2015). - PubMed - PMC - DOI

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Structural biology of CRISPR-Cas immunity and genome editing enzymes

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