Topoisomerase II-DNA cleavage complex (Top2-cc) (Top2-cc)

The Topoisomerase II-DNA cleavage complex (Top2-cc) is a transient, covalent intermediate formed during the catalytic cycle of type II topoisomerases, where the enzyme creates a double-strand break in DNA to allow the passage of another DNA duplex [1, 4, 10]. This complex is the primary molecular target for a class of potent anticancer drugs known as topoisomerase II poisons, such as etoposide and doxorubicin [2, 6, 14]. These drugs act by stabilizing the cleavage complex, preventing the religation of the DNA strands and leading to the accumulation of permanent double-strand breaks when the complex is encountered by cellular machinery like replication forks or RNA polymerases [7, 8, 13]. While essential for resolving topological constraints during DNA replication and chromosome segregation, the stabilization of this complex triggers apoptotic pathways in rapidly dividing cancer cells [3, 5, 9]. However, the formation of these complexes can also lead to genomic instability, contributing to side effects such as secondary leukemias and cardiotoxicity [4, 8, 11].

Other names

DNA / Topoisomerase II-DNA cleavage complexTopoisomerase II-DNA covalent complexTop2-DNA complexCleavable complexTop2ccTopoisomerase II-DNA adduct

Stabilization of the covalent enzyme-DNA cleavage complex (topoisomerase poisoning), which prevents the religation of DNA strands and leads to the accumulation of permanent double-strand breaks when the complex is encountered by cellular machinery such as replication forks or RNA polymerases [1, 4, 7, 10, 13].