Topoisomerase II alpha-DNA complex (Topoisomerase IIα-DNA complex (Topo IIα-DNA complex))

Topoisomerase II alpha is a type IIA topoisomerase enzyme crucial for managing DNA supercoiling, untangling chromosomes, and facilitating replication and segregation during the cell cycle. The pharmacologically relevant "Topoisomerase IIα-DNA complex" refers to the specific DNA-bound state that is targeted by many cancer therapeutics known as topoisomerase poisons. Drugs like etoposide function by stabilizing this cleavage complex, leading to accumulation of DNA double-strand breaks and cell death. The ability of topoisomerase IIα to form transient covalent bonds with DNA makes this complex uniquely susceptible to poisoning by anti-cancer agents, making it a pivotal therapeutic target. However, clinical targeting is challenged by significant safety concerns, notably therapy-related secondary malignancies and cardiotoxicity, often stemming from off-target poisoning of topoisomerase IIβ. Structural studies of this complex have generated valuable insights for rational drug design, including isoform-specific inhibition to improve safety. If further detail is needed for data structuring (e.g., gene identifiers, structure IDs), additional information can be extracted from cited protein structure resources.

Other names

Topoisomerase II alpha cleavage complexTOP2A-DNA complexDNA-bound Topoisomerase IIαHuman Topo IIα-DNA complex

*Topoisomerase poisons*: Stabilize the covalent Topoisomerase IIα-DNA cleavage complex, preventing religation and thus creating DNA double-strand breaks that trigger apoptosis. *Catalytic inhibitors*: Inhibit the enzyme's activity by targeting inactive conformations, not by stabilizing the cleavage complex.