DNA topoisomerase I–DNA complex (TopI–DNA complex)

The **DNA topoisomerase I–DNA complex** is a transient intermediate formed when DNA topoisomerase I, an essential enzyme, covalently binds to the DNA backbone during the process of relieving torsional strain in supercoiled DNA[1][2][3][7]. Type IB topoisomerases (including human topoisomerase I) cleave one strand of DNA via a catalytic tyrosine, creating a covalent enzyme–DNA complex which allows relaxation of superhelical tension by controlled rotation, followed by religation of the strand[1][2][5]. Certain anticancer drugs, especially the **camptothecin** class and their derivatives, “trap” the TopI–DNA complex by stabilizing the covalent intermediate and preventing religation, resulting in persistent DNA breaks and ultimately cell death. This makes the Topoisomerase I–DNA complex a validated therapeutic target in oncology, particularly in the treatment of solid tumors such as colorectal and ovarian cancers[1][7]. However, drug-induced stabilization of this complex can also generate genotoxicity in normal tissues, resulting in side effects and safety concerns. The accumulation of these complexes can serve as a pharmacodynamic biomarker of drug effect and is also linked to the efficacy and toxicity of topoisomerase I inhibitors[1][7].

Other names

Topoisomerase I–DNA adductTopI–DNA covalent complexDNA topoisomerase I cleavage complexTopoisomerase IB–DNA complex

Inhibitors such as camptothecin stabilize the covalent Topoisomerase I–DNA complex (“cleavage complex”), preventing religation and resulting in DNA single-strand and double-strand breaks, which lead to cytotoxicity and cell death[1][7].