DNA topoisomerase II-DNA cleavage complex (Topo II-DCC)

The DNA topoisomerase II-DNA cleavage complex is a transient catalytic intermediate formed during the enzyme's reaction cycle, where the protein is covalently linked to the 5' ends of a double-stranded DNA break (PubMed PMID: 19436320). Topoisomerase II enzymes, specifically the alpha (TOP2A) and beta (TOP2B) isoforms, are critical for managing DNA topology during replication, transcription, and chromosome segregation by passing one DNA duplex through another (UniProt P11388, P19012). Therapeutic agents known as topoisomerase II poisons, such as etoposide and doxorubicin, act by binding to and stabilizing this cleavage complex, effectively preventing the religation of the DNA strands (PubChem CID 36462). This stabilization converts an essential cellular enzyme into a potent toxin, leading to the accumulation of permanent DNA double-strand breaks that trigger programmed cell death (PubMed PMID: 23875711). While highly effective in treating various cancers, targeting this complex carries significant risks of genomic instability and secondary malignancies, such as leukemia, due to the persistence of DNA damage and chromosomal translocations (NIH/NCI; StatPearls).

Other names

Topoisomerase II-DNA covalent complexCleavable complexTopo II-DNA complexTopoisomerase II-DNA adduct

Stabilization of the covalent DNA-protein intermediate to prevent DNA religation, resulting in permanent double-strand breaks and induction of apoptosis.