DNA–topoisomerase II cleavage complex (Top2cc)

The DNA–topoisomerase II cleavage complex (Top2cc) is a transient catalytic intermediate formed during the action of topoisomerase II enzymes, which manage DNA topology by creating and resealing double-strand breaks (Pommier et al., 2016). During this process, the enzyme becomes covalently linked to the 5' ends of the DNA via a phosphotyrosyl bond. While essential for DNA replication, transcription, and chromosome segregation, the Top2cc is the primary target for a class of drugs known as topoisomerase poisons, such as etoposide and doxorubicin (Nitiss, 2009). These drugs stabilize the complex, preventing the religation of the DNA strands and leading to the accumulation of permanent double-strand breaks. In cancer cells, the resulting DNA damage triggers apoptotic pathways, making Top2cc a cornerstone of many chemotherapy regimens. However, the formation of these complexes can also lead to genomic instability and secondary malignancies, such as treatment-related leukemia (Ezoe et al., 2005). Bacterial versions of this complex are also targeted by fluoroquinolone antibiotics, which stabilize the cleavage complex in DNA gyrase and topoisomerase IV (StatPearls, 2023). Understanding the regulation and repair of Top2cc is vital for improving the efficacy and safety of these widely used clinical agents.

Other names

Topoisomerase II-DNA covalent complexTop2-DNA cleavage complexTop2ccTopoisomerase II-DNA complex

Stabilization of the transient covalent intermediate between topoisomerase II and DNA, preventing the religation of DNA strands and leading to the accumulation of double-strand breaks, which triggers apoptosis (Pommier et al., 2010).