DNA and topoisomerase II–DNA cleavage complexes (Topo II-DNA CC)

DNA and topoisomerase II–DNA cleavage complexes are transient intermediates formed during the catalytic cycle of topoisomerase II enzymes, which manage DNA topology by creating temporary double-strand breaks (Nitiss, 2009). These complexes consist of the enzyme covalently linked to the DNA backbone via a phosphotyrosyl bond. While essential for processes like DNA replication, transcription, and chromosome segregation, these complexes are the primary targets for a class of chemotherapy drugs known as topoisomerase II poisons (Pommier et al., 2010). Drugs such as etoposide and doxorubicin act by stabilizing these cleavage complexes, preventing the religation of the DNA strands. This stabilization leads to the accumulation of permanent double-strand breaks when the cell attempts to replicate or transcribe the damaged DNA, ultimately triggering apoptosis. Consequently, these complexes serve as a critical focal point for treating various malignancies, although their stabilization can also lead to significant side effects like cardiotoxicity and secondary cancers (Zhang et al., 2012).

Other names

Topoisomerase II-DNA covalent complexTopoisomerase II-DNA cleavable complexTopo II-DNA complex

Stabilization of the covalent DNA-topoisomerase II intermediate (cleavage complex), inhibiting DNA religation and inducing permanent double-strand breaks (Pommier et al., 2010).