New insights into DNA-binding by type IIA topoisomerases

► The WHD of type IIA topoisomerases exhibits a non-canonical DNA-binding mode. ► Packing of the two WHDs defines the cleavage pattern of type IIA topoisomerases. ► The wing-2 region of IIA enzyme's WHD mediates G-segment-bending. ► The Rossmann-like TOPRIM domain involves in catalysis as well as DNA-binding. ► The IIA enzyme-DNA interface can be targeted by antibiotics and anticancer drugs.