DNA topoisomerase I-DNA cleavage complex (Top1cc)

The DNA topoisomerase I-DNA cleavage complex (Top1cc) is a transient, covalent intermediate formed during the catalytic cycle of the DNA topoisomerase I (Top1) enzyme. Top1 is essential for relieving torsional strain (supercoiling) in DNA that arises during replication and transcription by inducing a single-strand break, allowing the DNA to rotate, and then religating the strand (1, 19, 22). In the presence of therapeutic agents known as topoisomerase poisons, such as camptothecin derivatives, this complex is stabilized and trapped, preventing the religation step (6, 14, 16). These trapped complexes become lethal lesions when they collide with advancing replication forks or transcription machinery, resulting in irreversible double-strand breaks and triggering programmed cell death (apoptosis) (2, 7, 14). Consequently, Top1cc is a major therapeutic target in oncology, with drugs like irinotecan and topotecan widely used to treat colorectal, ovarian, and lung cancers (3, 5, 15).

Other names

Top1-DNA covalent complexTop1-DNA cleavable complexTop1-DNA adductTop1-DNA intermediateTopoisomerase I-DNA complex

Interfacial inhibition; stabilization of the covalent Top1-DNA complex (trapping the cleavable complex) to prevent DNA religation, leading to replication fork collision, double-strand breaks, and apoptosis (1, 6, 16).