DNA topoisomerase II alpha and DNA topoisomerase II beta (Top2A (for alpha), Top2B (for beta))

DNA topoisomerase II alpha and II beta are essential nuclear enzymes that manage the topological states of DNA in eukaryotic cells by catalyzing the ATP-dependent passage of one DNA double helix through another via transient double-strand breaks. Topoisomerase II alpha (encoded by TOP2A) is crucial for chromosome condensation, decatenation, and segregation during mitosis and is highly expressed in proliferating cells, making it a key marker for cell proliferation and a major anticancer drug target. Topoisomerase II beta (TOP2B) plays critical roles in transcriptional regulation and neural development, but is dispensable for cell division in most cell types. Both isoforms are targeted by multiple chemotherapeutic drugs, which exploit their cleavage activity to induce cytotoxic double-strand breaks in cancer cells; inhibition or mutation of these enzymes can result in disease, impact drug responses, and pose significant safety concerns, including risk for secondary malignancies.

Other names

DNA topoisomerase IIα (TOP2A)DNA topoisomerase IIβ (TOP2B)Topoisomerase II alphaTopoisomerase II betaTop2ATop2BType II topoisomerase (general, but not isoform-specific)

Stabilization of Topo II-DNA cleavage complex (leading to double-strand DNA breaks and cell death); Inhibition of ATPase activity; Inhibition of catalytic activity, leading to prevention of relegation of DNA and generation of cytotoxic DNA damage