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CRISPR–Cas adaptation: insights into the mechanism of action

Nature Reviews Microbiology volume 14, pages 67–76 (2016)Cite this article

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Abstract

Since the first demonstration that CRISPR–Cas systems provide bacteria and archaea with adaptive immunity against phages and plasmids, numerous studies have yielded key insights into the molecular mechanisms governing how these systems attack and degrade foreign DNA. However, the molecular mechanisms underlying the adaptation stage, in which new immunological memory is formed, have until recently represented a major unresolved question. In this Progress article, we discuss recent discoveries that have shown both how foreign DNA is identified by the CRISPR–Cas adaptation machinery and the molecular basis for its integration into the chromosome to form an immunological memory. Furthermore, we describe the roles of each of the specific CRISPR–Cas components that are involved in memory formation, and consider current models for their evolutionary origin.

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Figure 1: The three stages of CRISPR–Cas immunity.
Figure 2: Discrimination between self and non-self DNA in type I-E CRISPR–Cas system adaptation.
Figure 3: Spacer integration into the CRISPR array.

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Acknowledgements

The authors thank P. Fineran for discussions on primed acquisition. R.S. was supported, in part, by the Israel Science Foundation (personal grant 1303/12 and Israeli Centers of Research Excellence (I-CORE) grant 1796/12), the European Research Council (ERC; Starting Grant 260432), the Human Frontier Science Program (HFSP; grant RGP0011/2013), the Abisch-Frenkel foundation, the Pasteur-Weizmann council, the Institut Merieux, the Leona M. and Harry B. Helmsley Charitable Trust, the Minerva Foundation and the Deutsche Forschungsgemeinschaft (a Deutsch-Israelische Projektkooperation (DIP) grant).

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  1. Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, 76100, Israel

    Gil Amitai & Rotem Sorek

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Correspondence to Rotem Sorek.

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Amitai, G., Sorek, R. CRISPR–Cas adaptation: insights into the mechanism of action. Nat Rev Microbiol 14, 67–76 (2016). https://doi.org/10.1038/nrmicro.2015.14

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