Discovery helps improve accuracy of CRISPR-Cas9 gene editing

The Cas9 protein (gray) is an RNA-guided nuclease that can be programmed to bind and cut any matching DNA sequence (dark blue double helix), making it a powerful tool for genome engineering. Upon target binding, Cas9 protein domains undergo conformational rearrangements (the motions of individual amino acids are represented by rocket tails) to activate the Cas9-sgRNA complex for target cleavage. The REC3 domain (teal) is responsible for target sensing, which signals the outward rotation of the REC2 domain (magenta) to open a path for the HNH nuclease domain (yellow). This active conformation of Cas9 is then capable of triggering concerted cleavage of both strands of the target DNA. Credit: Janet Iwasa graphic for Doudna Lab