DNA–Topoisomerase II complex (Topo II-DNA complex)

The DNA–Topoisomerase II complex is a transient intermediate formed during the catalytic cycle of topoisomerase II enzymes, which are essential for managing DNA topology during replication, transcription, and chromosome segregation (Source: PubMed, PMID: 23856310). This complex involves the enzyme creating a double-strand break in DNA and becoming covalently attached to the 5' ends of the DNA backbone via a phosphotyrosyl linkage (Source: UniProt, P11388). As a therapeutic target, this complex is primarily exploited by "topoisomerase II poisons," such as etoposide and anthracyclines, which stabilize the cleavage complex and prevent DNA religation (Source: StatPearls, NBK546664). The stabilization of these complexes leads to the accumulation of permanent double-strand breaks, which triggers apoptosis in rapidly dividing cells, making it a cornerstone of cancer chemotherapy (Source: NIH, National Cancer Institute). However, targeting this complex is associated with significant risks, including cardiotoxicity—linked to the TOP2B isoform in cardiomyocytes—and the development of secondary leukemias due to chromosomal translocations (Source: PubMed, PMID: 21947482).

Other names

Topoisomerase II-DNA cleavage complexTIICCDNA-Topo II complexDNA-Topoisomerase 2 complex

Topoisomerase II poisons stabilize the covalent DNA-protein cleavage complex, preventing DNA religation and inducing lethal double-strand breaks and apoptosis.