DNA topoisomerase 2-alpha (TOP2A)

DNA topoisomerase 2-alpha (TOP2A) is an essential eukaryotic type IIA topoisomerase that functions as a homodimer to alter DNA topology by creating transient, ATP‑dependent double‑strand breaks and passing a second DNA segment through the break; it is crucial for decatenation of sister chromatids, chromosome condensation, and faithful chromosome segregation in proliferating cells. Human Top2α is the primary isoform targeted by frontline anticancer agents that form ternary drug–enzyme–DNA cleavage complexes; structural and cryo‑EM studies reveal the “two‑gate” mechanism, active‑site residues (including catalytic Tyr805 in human Top2α), and allosteric coupling between the ATPase and DNA‑cleavage cores that underlie drug action and opportunities for isoform‑selective inhibition.

Other names

Topoisomerase II alphaTop2αDNA topoisomerase II alphahTopo IIα

Topoisomerase II poison: drugs such as doxorubicin and etoposide stabilize the Top2α–DNA cleavage complex, producing persistent double‑strand breaks that trigger cell death in dividing cells