DNA–topoisomerase I cleavage complex (Top1cc) (Top1cc)

The DNA–topoisomerase I cleavage complex (Top1cc) is a transient intermediate formed during the catalytic cycle of topoisomerase I, an essential enzyme that relieves torsional strain in DNA during replication and transcription (Pommier, 2006; PubMed: 16988639). Topoisomerase I functions by creating a reversible single-strand break, allowing the DNA to rotate and relax before religating the strand (Pommier et al., 2016; PubMed: 27149133). Therapeutic agents known as Top1 inhibitors, such as camptothecin derivatives, specifically bind to and stabilize this covalent complex, preventing the religation step (StatPearls, 2023; NBK547691). When the moving replication fork or transcription machinery encounters these trapped complexes, the single-strand nicks are converted into irreversible double-strand breaks, triggering DNA damage responses and programmed cell death (Pommier, 2013; PubMed: 23548772). This mechanism is particularly effective against rapidly dividing cancer cells, making Top1cc a critical target in the treatment of various malignancies, including colorectal, lung, and ovarian cancers (NIH, 2023). However, the clinical use of drugs targeting this complex is often limited by significant toxicities, most notably bone marrow suppression and severe gastrointestinal distress (PubChem, 2024).

Other names

Topoisomerase I-DNA complexTop1-DNA covalent complexDNA-topoisomerase I complexTop1ccTopoisomerase I-DNA cleavage complex

Stabilization of the transient covalent DNA-topoisomerase I complex (cleavage complex), which prevents DNA religation and leads to lethal double-strand breaks upon collision with replication forks.