DNA topoisomerase II (Top2)

DNA topoisomerase II is an essential ATP-dependent enzyme that manages the topology of double-stranded DNA by introducing transient double-strand breaks. This allows it to resolve supercoils, untangle intertwined chromosomes, and facilitate proper chromosome segregation during cell division. The human genome encodes two isoforms—TOP2A and TOP2B—with distinct but overlapping roles. Many anticancer drugs exploit this target by either stabilizing the normally transient cleavage complex formed between the enzyme and cleaved DNA (“topoisomerase poisons,” e.g., etoposide, doxorubicin), or by intercalating into the DNA itself to disrupt enzymatic activity. These mechanisms can lead to cytotoxic double-strand breaks if not properly repaired. Bacterial type II topoisomerases are also important antibiotic targets.

Other names

Type II topoisomeraseTop2Topo IIDNA gyrase (bacterial)Topoisomerase IV (bacterial)TOP2A/TOP2B (human isoforms)

Inhibition of enzyme activity by stabilizing the covalent cleavage complex between topoisomerase II and DNA (“poisoning”); Intercalation into DNA to disrupt enzyme function.