Deoxyribonucleic acid in topoisomerase-DNA complexes (DNA-Topo complex)

DNA in topoisomerase-DNA complexes refers to the transient intermediate formed when topoisomerase enzymes bind and cleave DNA to manage topological constraints during replication and transcription (Pommier, 2013, Nature Reviews Cancer). These complexes, often termed "cleavable complexes," involve a covalent phosphotyrosyl bond between the enzyme and the DNA backbone (Nitiss, 2009, Nature Reviews Cancer). While essential for normal cellular function, these complexes are the primary pharmacological targets for topoisomerase poisons used in chemotherapy and antibacterial treatment. Drugs like irinotecan and etoposide stabilize these intermediates, preventing the religation of DNA strands and converting them into permanent, lethal DNA lesions (Pommier, 2006, Nature Reviews Cancer). The accumulation of these stabilized complexes triggers the DNA damage response, leading to programmed cell death in rapidly proliferating cells (Deweese & Osheroff, 2009, Nucleic Acids Research). This mechanism is exploited to treat various cancers and, in the case of fluoroquinolones targeting bacterial gyrase, to treat infectious diseases (Drlica et al., 2008, Microbiology and Molecular Biology Reviews).

Other names

DNA-topoisomerase cleavable complexTopoisomerase-DNA covalent complexDNA-protein crosslinkCleavable complex

Stabilization of the covalent DNA-topoisomerase intermediate (cleavable complex) to prevent DNA religation, resulting in permanent DNA strand breaks and induction of apoptosis.