DNA topoisomerase II – DNA complex (TOP2-DNA complex)

DNA topoisomerase II (TOP2) is an essential enzyme that manages DNA topology by creating transient double-strand breaks to allow one DNA duplex to pass through another during replication and transcription (Source: UniProt P11388). The "DNA topoisomerase II – DNA complex" refers to the covalent intermediate, also known as the cleavage complex (TOP2cc), where the enzyme is linked to the DNA backbone (Source: PubMed PMID: 23875711). This complex is the primary target for "topoisomerase II poisons," a class of potent anticancer drugs including etoposide and doxorubicin (Source: StatPearls, "Topoisomerase Inhibitors"). These drugs act by stabilizing the cleavage complex, preventing the re-ligation of DNA and effectively converting the enzyme into a source of lethal DNA damage (Source: PubMed PMID: 19713902). While targeting the TOP2A isoform in this complex is effective against rapidly proliferating cancer cells, interaction with the TOP2B isoform in cardiac tissue is a major cause of drug-induced cardiotoxicity (Source: PubMed PMID: 23045665). Furthermore, the persistence of these complexes can lead to chromosomal translocations, posing a risk for the development of secondary malignancies such as acute myeloid leukemia (Source: PubMed PMID: 15186530).

Other names

TOP2 cleavage complexTOP2ccTopoisomerase II-DNA covalent complexDNA topoisomerase 2-DNA complex

Stabilization of the covalent DNA-protein intermediate (cleavage complex), preventing DNA re-ligation and inducing apoptosis via double-strand breaks.