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Article summary:

1. IscB, a transposon-encoded nuclease, shares structural and mechanistic similarities with Cas9 in RNA-guided DNA cleavage.

2. The IscB-ωRNA RNP complex uses a target-adjacent motif (TAM) to recognize the target site and forms an R-loop for DNA cleavage.

3. The PLMP domain in IscB is dispensable for RNA-guided DNA cleavage, and engineering of stealthier versions of IscB can improve its genome-editing activity in human cells.

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