DNA topoisomerase I (TOP1) (TOP1)

DNA topoisomerase I (TOP1) is an essential nuclear enzyme responsible for relieving the torsional strain (supercoiling) that occurs during DNA replication, transcription, and repair (UniProt P11387). It functions by creating transient single-strand breaks in the phosphodiester backbone of DNA, allowing the strand to rotate before religation. Because rapidly dividing cancer cells rely heavily on TOP1 to maintain genomic integrity during high rates of replication, the enzyme is a major target for oncology therapeutics (PubMed: 29115199). Inhibitors such as irinotecan and its liposomal formulation (Onivyde) bind to the TOP1-DNA complex, preventing the religation step and causing the formation of permanent double-strand breaks when replication forks collide with the stalled complexes (FDA Label: Onivyde). This process induces DNA damage responses and eventually leads to programmed cell death (apoptosis) in malignant cells (StatPearls: Topoisomerase Inhibitors).

Other names

Topoisomerase ITOP1DNA topoisomerase 1Type I DNA topoisomerase

Inhibition of DNA topoisomerase I by stabilizing the covalent TOP1-DNA cleavage complex, which prevents DNA religation and leads to lethal double-strand breaks during DNA replication (PubMed: 16557226).