DNA topoisomerase II enzyme (Topo II)

DNA topoisomerase II is an essential ATP-dependent enzyme that manages the topology of double-stranded DNA. It functions by creating transient double-strand breaks in the DNA helix, allowing another segment of duplex DNA to pass through before resealing the break. This process relieves torsional stress generated during replication and transcription and ensures proper chromosome segregation during mitosis. In eukaryotes there are two main isoforms—topo IIα and topo IIβ—with distinct but overlapping roles. The enzyme is a critical target for several anticancer drugs that exploit its mechanism by stabilizing its cleavage complex with DNA, thereby inducing lethal genetic damage preferentially in rapidly dividing tumor cells.

Other names

Topoisomerase IIType II topoisomeraseDNA gyrase (in prokaryotes, specifically for the bacterial form)Topo IIα (for the alpha isoform in eukaryotes)Topo IIβ (for the beta isoform in eukaryotes)

Drugs targeting this molecule typically act as **topoisomerase poisons**—they stabilize the transient double-strand break created by topoisomerase II, preventing religation and leading to accumulation of double-stranded breaks, which triggers apoptosis in rapidly dividing cells such as cancer cells.