DNA-Topoisomerase II complex (TOP2cc) (TOP2cc)

The DNA-Topoisomerase II complex is a transient intermediate formed during the catalytic cycle of Topoisomerase II enzymes, which are essential for managing DNA supercoiling, knotting, and catenation (Nitiss, 2009). These enzymes function by creating a double-strand break in one DNA duplex, passing a second duplex through the gate, and then religating the broken strands (UniProt, 2024). The interface between the DNA and the enzyme is the primary target for "topoisomerase II poisons," a potent class of anticancer drugs including etoposide and doxorubicin, as well as certain antibacterial agents like fluoroquinolones that target the bacterial homologs (PubMed, 2023). These agents intercalate or bind at the cleavage site, trapping the enzyme in a covalent complex with the DNA and preventing the religation step (Pommier, 2013). This conversion of an essential enzyme into a cellular toxin results in the accumulation of double-strand breaks, which trigger apoptosis in rapidly dividing cancer cells or cell death in bacteria (NIH, 2023). However, the clinical use of these drugs is limited by significant safety concerns, most notably dose-dependent cardiotoxicity and the risk of secondary malignancies like acute myeloid leukemia (StatPearls, 2023).

Other names

Topoisomerase II-DNA cleavage complexTOP2ccDNA-Topoisomerase II interfaceTopoisomerase II-DNA binary complex

Stabilization of the covalent DNA-Topoisomerase II cleavage complex (TOP2cc), which prevents DNA religation and leads to double-strand breaks and apoptosis (Pommier, 2013; StatPearls, 2023).