DNA Topoisomerase II (TOP2) (TOP2)

DNA Topoisomerase II (TOP2) is an essential enzyme that manages DNA supercoiling and tangling by creating transient double-strand breaks in the DNA phosphodiester backbone (UniProt P11388). This activity is crucial for fundamental cellular processes including DNA replication, transcription, and the segregation of daughter chromosomes during mitosis (StatPearls, NBK545232). In clinical oncology, Topoisomerase II is a major target for several classes of chemotherapy, including anthracyclines like doxorubicin and epipodophyllotoxins like etoposide (NCI Drug Dictionary). These drugs typically function as "topoisomerase poisons," which stabilize the enzyme-DNA cleavage complex and prevent DNA religation, ultimately triggering apoptosis (PubMed, PMID: 23511449). The inclusion of "cellular membranes and macromolecules" in this context likely refers to the multi-modal toxicity of certain agents like anthracyclines, which also intercalate into DNA and generate reactive oxygen species that cause lipid peroxidation and damage to various cellular structures (PubChem CID 31703). Consequently, while these mechanisms are effective against rapidly dividing cancer cells, they are also associated with significant adverse effects, most notably permanent cardiotoxicity (PubMed, PMID: 28438235).

Other names

Topoisomerase IIDNA Topoisomerase 2TOP2ATOP2BTopoisomerase II alphaTopoisomerase II beta

Stabilization of the topoisomerase II-DNA cleavage complex (topoisomerase poisoning), DNA intercalation, and generation of reactive oxygen species (ROS) leading to macromolecular damage.