Cas9 slide-and-seek for phage defense and genome engineering

How does the Cas9 nuclease locate a specific 20‐nucleotide target sequence in a crowded intracellular environment packed with mega bases of distracting non‐target DNA? Previously, it was shown that Cas9 finds DNA targets via three‐dimensional diffusion. In this issue of The EMBO Journal, Globyte et al (2019) reveal another dimension of the search process, which involves short‐range one‐dimensional sliding. These results have implications for understanding the natural function of Cas9 and its applications in genome engineering experiments.

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