DNA topoisomerase 2 (Topoisomerase II) (Topo II)

DNA topoisomerase 2 (Topo II) is an essential nuclear enzyme that manages the topological state of DNA by generating transient double-strand breaks, allowing one DNA duplex to pass through another. This catalytic activity is vital for fundamental cellular processes including DNA replication, transcription, and the proper segregation of daughter chromosomes during mitosis (Source: UniProt P11388, P19012). The Topo II–DNA cleavable complex is a specific intermediate state in the enzyme's reaction cycle where the protein is covalently linked to the broken DNA backbone. Many potent anticancer drugs, known as Topo II poisons, act by trapping this cleavable complex, effectively converting the enzyme into a DNA-damaging agent that triggers programmed cell death (Source: PubMed PMID: 21572414). Because of its critical role in rapidly dividing cells, Topo II is a primary target for chemotherapy in treating various solid tumors and hematological malignancies (Source: StatPearls, "Topoisomerase Inhibitors"). However, clinical use of these agents is often constrained by significant safety concerns, most notably the risk of permanent cardiotoxicity and the development of secondary leukemias due to off-target genomic instability (Source: PubMed PMID: 19301284).

Other names

TOP2DNA topoisomerase IITopoisomerase 2-alphaTopoisomerase 2-betaTOP2ATOP2BDNA gyrase (bacterial homolog)Topo II-DNA covalent complex

Stabilization of the Topoisomerase II-DNA covalent cleavable complex, which prevents the re-ligation of DNA strands and leads to the accumulation of double-strand breaks and subsequent apoptosis.