DNA-topoisomerase II cleavable complex (Topo II-DNA CC)

The DNA-topoisomerase II cleavable complex is a transient, covalent intermediate formed during the catalytic cycle of topoisomerase II enzymes, which are essential for managing DNA topology during replication, transcription, and chromosome segregation [1, 2]. In this state, the enzyme creates a double-strand break in the DNA backbone and remains covalently linked to the 5' phosphate ends via active-site tyrosine residues [3, 5]. While this complex is normally short-lived and quickly religated, topoisomerase II poisons—a class of potent anticancer drugs—interact with the enzyme to stabilize this intermediate and prevent DNA religation [4, 6]. This stabilization converts the enzyme into a cellular toxin, resulting in the accumulation of permanent double-strand breaks that trigger programmed cell death [3, 11]. This mechanism is a cornerstone of treatment for various cancers, including leukemias, lymphomas, and solid tumors like breast and lung cancer [6, 15]. However, the induction of DNA damage by these complexes also carries risks, such as the development of therapy-related secondary malignancies and significant systemic toxicities like myelosuppression and cardiotoxicity [3, 4].

Other names

Topoisomerase II-DNA covalent complexTopo II cleavage complexDNA-topoisomerase II adductTopoisomerase II-DNA cleavable complexTOP2cc

Stabilization of the transient covalent topoisomerase II-DNA cleavable complex, which prevents DNA religation and converts the enzyme into a cellular toxin that induces permanent double-strand breaks and triggers apoptosis.