DNA topoisomerase I-DNA complex (Topo I)

DNA topoisomerase I is a ubiquitous enzyme present in all domains of life that modifies DNA topology by creating transient single-strand breaks, allowing relaxation of supercoiled DNA necessary for replication, transcription, and chromosome segregation. In its catalytic cycle, topoisomerase I forms a short-lived covalent intermediate with DNA via a tyrosine residue in its active site ("DNA topoisomerase I-DNA complex") before religating the strand; therapeutic inhibition stabilizes this complex, converting a transient step into a cytotoxic lesion. Drugs exploiting this mechanism are used primarily in cancer chemotherapy and act as "topoisomerase poisons" by arresting the religation step and promoting persistent DNA damage that triggers cell death, especially in tumor cells with defective DNA damage checkpoints.

Other names

Topoisomerase ITopo IType I DNA topoisomeraseDNA topoisomerase type I

Topoisomerase I inhibitors bind and stabilize the Topoisomerase I-DNA covalent complex, preventing religation of the nicked DNA strand and inducing single-strand breaks, ultimately leading to replication fork collapse, double-strand breaks, apoptosis, and cell death