CRISPR/Cas9-based DNA targeting has quickly become a leading tool in the fields of synthetic biology and genome engineering. It exploits the ability of a bacterial endonuclease, Cas9, guided by an RNA molecule, to target virtually any matching DNA sequence of interest for binding and/or cleavage. A study published in this issue of Nature reports the use of single-molecule and bulk biochemical experiments to reveal the mechanism by which RNA-guided Cas9 locates unique 20-base-pair sequences within DNA genomes, which can be billions of base pairs long.
The results highlight the role of a trinucleotide protospacer adjacent motif (PAM; yellow in the cover image) in recruiting Cas9–RNA complexes to potential DNA target sites, and in catalytically activating the nuclease (outlined in brown). Target DNA sequences are recognized via a ‘zip-up‘ mechanism, where the sequential formation of RNA–DNA base pairs (red) offsets the energetic cost of unwinding the DNA double helix (purple and blue). In addition to its relevance for gene manipulation, this work reveals how DNA is interrogated by Cas9–RNA in its role as an effector of adaptive immunity in bacteria. Cover: K.C. Roeyer.
From the Art Desk:
Art Director, Kelly Krause, explains:
“This cover is a fantastic example of visual storytelling. We can see the CRISPR process going on in the centre, with a real sense of action and movement, as well as the manipulated genes in the background, giving a sense of time and context.
“The artist has done a wonderful job of conveying a complex process simply and beautifully, using colour and composition to convey key information.”