DNA topoisomerase–DNA complex

The **topoisomerase–DNA complex** refers to a transient, functionally essential intermediate formed during the catalytic cycle of DNA topoisomerases, enzymes that resolve topological problems in DNA by transiently cleaving one or both strands to allow strand passage, relaxation, or untangling. Therapeutically, "trapping" this complex (i.e., preventing re-ligation of the DNA) is key to the cytotoxicity of several classes of anticancer drugs and antibiotics. This leads to persistent DNA breaks and cell death, especially in rapidly dividing cells. While this complex is critical in both normal physiology and as a drug target, the term describes an enzyme–substrate intermediate, not a specific protein or receptor. **Important note:** For most applications, **"Topoisomerase–DNA complex"** is not a canonical drug target name but a description of a key druggable complex state that arises during topoisomerase action and is exploited pharmacologically. Therapeutic databases typically list specific protein entities (e.g., DNA topoisomerase II alpha), not complexes per se.

Other names

Topoisomerase–DNA covalent complexTopoisomerase cleavage complexDNA–topoisomerase complexTopo–DNA adduct

Drugs targeting the topoisomerase–DNA complex generally: - Stabilize the transient cleavage complex (covalent topoisomerase–DNA intermediate) and prevent religation, causing accumulation of DNA breaks, leading to cell death (cytotoxicity). - For example, **etoposide** traps TopoII–DNA cleavage complexes, inducing DNA double-strand breaks. - **Camptothecin** analogs trap TopoI–DNA single-strand breaks. - **Fluoroquinolones** trap bacterial topoisomerase–DNA complexes, leading to DNA fragmentation.