DNA-topoisomerase II alpha complex (DNA-TOP2A complex) (DNA-TOP2A complex)

The DNA-topoisomerase II complex is a critical transient intermediate formed during the catalytic cycle of topoisomerase II enzymes, which manage DNA supercoiling and catenation by creating double-strand breaks (StatPearls, 2023). In proliferating cells, the alpha isoform (TOP2A) is significantly upregulated during the S and G2/M phases to facilitate essential processes such as DNA replication and chromosome segregation (UniProt P11388). This complex is the primary molecular target for a class of chemotherapy drugs known as topoisomerase II poisons, including etoposide and anthracyclines like doxorubicin (PubMed, PMID: 23875711). These agents act by stabilizing the covalent DNA-protein intermediate, often called the 'cleavable complex,' which prevents the enzyme from religating the DNA strands (Nature Reviews Cancer, 2009). The resulting accumulation of double-strand breaks triggers genomic instability and programmed cell death in rapidly dividing cancer cells. While highly effective, targeting this complex is associated with significant clinical challenges, including dose-dependent cardiotoxicity and the risk of secondary leukemias due to off-target DNA damage (NIH, 2022).

Other names

Topoisomerase II-DNA cleavable complexTOP2-DNA covalent complexTopoisomerase II-DNA binary complexDNA-TOP2 complex

Stabilization of the covalent DNA-topoisomerase II intermediate (cleavable complex), which prevents DNA religation and converts the enzyme into a cellular toxin that induces permanent double-strand breaks and apoptosis (PubMed, PMID: 19373244).