PerspectiveStructural Biology

Cas9, poised for DNA cleavage

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Science  19 Feb 2016:
Vol. 351, Issue 6275, pp. 811-812
DOI: 10.1126/science.aaf2089

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Summary

Over the past 3 years, the technique known as CRISPR—clustered regularly interspaced short palindromic repeats—has revolutionized the field of genome editing (1). A single enzyme called CRISPR-associated protein 9 (Cas9) can be programmed with CRISPR-derived RNAs (crRNAs) to introduce double-stranded DNA (dsDNA) breaks at specific sites in the genome. On page 867 of this issue, Jiang et al. (2) describe structures of Streptococcus pyogenes Cas9 captured in a state poised for DNA cleavage. This new snapshot, together with those from previous structures, explains how binding to a dsDNA target allosterically activates DNA cleavage by the Cas9 endonuclease.