DNA topoisomerase-DNA cleavage complex (Topo-DNA CC) (Topo-DNA CC)

The DNA topoisomerase-DNA cleavage complex is a transient, covalent intermediate formed during the catalytic cycle of topoisomerase enzymes as they resolve topological strain in DNA (Pommier, 2013). These enzymes are essential for processes such as DNA replication, transcription, and chromosome segregation by creating temporary single- or double-strand breaks (Nitiss, 2009). In the context of oncology, this complex is the specific target of topoisomerase poisons, which trap the enzyme on the DNA, preventing the religation of the phosphodiester backbone (StatPearls, 2023). When the replication machinery or RNA polymerase encounters these stabilized complexes, it leads to the formation of permanent, lethal DNA double-strand breaks (Pommier, 2013). Tumor cells are often more susceptible to this damage due to their rapid proliferation rates and potential defects in DNA repair pathways (NIH, 2022). Consequently, targeting this complex remains a cornerstone of chemotherapy for various solid tumors and hematological malignancies (Nitiss, 2009). The stabilization of this complex is distinct from catalytic inhibition, as it converts an essential enzyme into a cellular toxin (Pommier, 2013). Clinical efficacy is often limited by the development of resistance mechanisms, such as the upregulation of repair enzymes like tyrosyl-DNA phosphodiesterase 1 (Delgado et al., 2018).

Other names

Topoisomerase cleavage complexTopoCCTopoisomerase-DNA covalent complexTopoisomerase-DNA adductTopoisomerase-DNA intermediate

Stabilization of the transient covalent intermediate formed between topoisomerase enzymes and DNA, preventing the religation of DNA strands and leading to lethal double-strand breaks during replication (Pommier, 2013; StatPearls, 2023).