Molecular mechanisms of CRISPR–Cas spacer acquisition

Abstract

Many bacteria and archaea have the unique ability to heritably alter their genomes by incorporating small fragments of foreign DNA, called spacers, into CRISPR loci. Once transcribed and processed into individual CRISPR RNAs, spacer sequences guide Cas effector nucleases to destroy complementary, invading nucleic acids. Collectively, these two processes are known as the CRISPR–Cas immune response. In this Progress article, we review recent studies that have advanced our understanding of the molecular mechanisms underlying spacer acquisition and that have revealed a fundamental link between the two phases of CRISPR immunity that ensures optimal immunity from newly acquired spacers. Finally, we highlight important open questions and discuss the potential basic and applied impact of spacer acquisition research.

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Fig. 1: Integration of new spacers into the CRISPR locus.
Fig. 2: Protospacer selection and capture.

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Acknowledgements

The authors thank the members of the laboratory for helpful discussions. J.M. is supported by a US National Science Foundation Graduate Research Fellowship. L.A.M. is supported by a Burroughs Wellcome PATH Award, a National Institutes of Health (NIH) Director’s Pioneer Award (DP1GM128184-01) and an HHMI-Simons Faculty Scholar Award.

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Nature Reviews Microbiology thanks K. Severinov and the other anonymous reviewer(s) for their contribution to the peer review of this work.

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J.M. researched data for the article. J.M. and L.A.M. made substantial contributions to discussions of the content, wrote the article and reviewed and/or edited the manuscript before submission.

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Correspondence to Luciano A. Marraffini.

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McGinn, J., Marraffini, L.A. Molecular mechanisms of CRISPR–Cas spacer acquisition. Nat Rev Microbiol 17, 7–12 (2019). https://doi.org/10.1038/s41579-018-0071-7

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