The DdmDE defense system eradicates plasmids by target-centered bidirectional ssDNA loop extrusion and site-specific cleavage
Yang et al. reveal a dynamic DdmDE-mediated plasmid clearance pathway. Transient DNA bubbles permit promiscuous DdmE binding, while target specificity arises from slower dissociation at matched sites. DdmE then recruits a DdmD dimer to drive target-centered, bidirectional dsDNA unwinding. Free DdmD subsequently coats extruded ssDNA to enable site-specific endonucleolytic cleavage.