DNA topoisomerase II-DNA cleavable complex (Topo II-DNA CC)

The DNA topoisomerase II-DNA cleavable complex is a transient catalytic intermediate formed during the action of type II topoisomerases, which are essential enzymes that manage DNA topology by creating transient double-strand breaks [4, 7]. In this complex, the enzyme is covalently linked to the 5'-phosphoryl ends of the DNA through a phosphotyrosyl bond, maintaining genomic integrity while a second DNA duplex is passed through the break [8, 10]. This intermediate is the primary molecular target for "topoisomerase II poisons," a class of potent anticancer and antibacterial agents including etoposide, doxorubicin, and quinolones [1, 3, 6]. These drugs act by stabilizing the cleavable complex and preventing the religation of the DNA strands, which leads to the accumulation of permanent double-strand breaks when the complex encounters replication or transcription machinery [3, 5]. The resulting DNA damage triggers apoptotic pathways, making this complex a key target for treating various malignancies [2, 3]. However, the stabilization of these complexes can also lead to chromosomal translocations, posing a risk for secondary malignancies such as therapy-related leukemia [4, 5].

Other names

Topoisomerase II-DNA cleavage complexTopo II-DNA covalent complexTopoisomerase II-DNA phosphotyrosyl complexTopo II-DNA adduct

Topoisomerase II poisons stabilize the covalent intermediate (cleavable complex) where the enzyme is linked to the 5' ends of the broken DNA, preventing religation and causing lethal double-strand breaks [1, 3, 5].