DNA topoisomerase II alpha–DNA complex (TOP2A–DNA complex)

DNA topoisomerase II alpha (TOP2A) is a vital nuclear enzyme that controls DNA topology by catalyzing the ATP-dependent passage of one double-stranded DNA segment through a transient double-stranded break in another segment, a reaction essential for DNA replication, chromosome segregation, and transcription[4][7][1]. The enzyme forms a homodimer and interacts closely with DNA, bending and cleaving it at specific sites as part of its catalytic cycle[2][7]. Antineoplastic (anticancer) drugs such as etoposide, doxorubicin, and others act by stabilizing the transient TOP2A–DNA cleavage complex, thereby preventing DNA religation and causing persistent double-stranded breaks that trigger cell death[9][7]. This mechanism underlies the therapeutic efficacy of these drugs in proliferating cancer cells, but also poses risks for secondary malignancies due to genome instability. The structure and regulation of the TOP2A–DNA complex, particularly at the catalytic and C-terminal domains, are active areas of research for developing more selective and less toxic cancer therapeutics[4][9][7].\n\nNote on is_incorrect: “Topoisomerase IIα / DNA complex” refers not to a unique molecule but to the transient, drug-targeted intermediate formed when DNA topoisomerase IIα is covalently linked to DNA at a double-strand break site. This is a relevant drug target state but not a standalone protein, so the entry is somewhat non-canonical as a molecular target and should be flagged as such[9][7].

Other names

Topoisomerase IIα–DNA complexHuman topoisomerase IIα–DNA complexTOP2A–DNA cleavage complex

Stabilization of TOP2A–DNA cleavage complex (poisons); Induction of persistent double-stranded DNA breaks; Inhibition of DNA religation/re-ligation