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Beschreibung

DNA topoisomerase 1 (EC 5.99.1.2, UniProt P11387, also known as DNA topoisomerase I, Topo I) is encoded by the TOP1 (also known as TOPI) gene (Gene ID 7150) in human. Topo I relaxes double strand DNA (dsDNA) torsional strain by nicking one strand of the dsDNA to allow rotation of the nicked 3'-hydroxy end around the unnicked strand, while the 5'-phosphoryl end of the nicked DNA forms a covalent phosphodiester bond with a tyrosine residue on Topo I. The nicked 3'-hydroxy end then attacks the DNA-enzyme phosphoester bond to religate the nicked DNA strand. One supercoil is removed during each round of Topo I-catalyzed nicking and resealing. Camptothecins are widely used for cancer treatment, these drugs intercalate into DNA at the topo I active site, inhibiting the religation step of the enzyme and shifting the equilibrium toward covalent topo I-DNA complexes rather than free topo I and DNA. Interaction of these drug-stabilized covalent topo I-DNA complexes with advancing replication forks or transcription complexes causse further DNA damage and eventual cell death.