DNA topoisomerase I and II (TOP1/TOP2)

DNA topoisomerases I and II are nuclear enzymes that control the topological state of DNA during essential cellular processes such as replication, transcription, and chromosome segregation [PMID: 19373244]. Topoisomerase I (TOP1) functions by creating transient single-strand breaks to relax DNA supercoiling, whereas Topoisomerase II (TOP2) creates double-strand breaks to resolve DNA knots and catenanes [PMID: 23549241]. These enzymes are frequently overexpressed in rapidly dividing cancer cells, making them prime targets for chemotherapy. Therapeutic agents, often referred to as topoisomerase poisons, work by trapping the enzyme in a covalent complex with DNA, known as the cleavable complex. This entrapment prevents the religation of DNA strands, leading to the accumulation of permanent DNA damage and subsequent cell death via apoptosis [PMID: 19373244]. While highly effective in treating various malignancies, including lung, ovarian, and colorectal cancers, these drugs are associated with significant toxicities such as myelosuppression and, in the case of TOP2 inhibitors, potential cardiotoxicity and secondary malignancies [PMID: 20592731].

Other names

Topoisomerase I/IITOP1/TOP2DNA-topoisomerase complexTopoisomerase-DNA cleavable complex

Stabilization of the covalent cleavable complex between the topoisomerase enzyme and DNA, preventing DNA religation and inducing lethal DNA strand breaks.