Comparison of effects of fostriecin, novobiocin, and camptothecin, inhibitors of DNA topoisomerases, on DNA replication and repair in human cells.
Fostriecin causes a delayed inhibition of replicative DNA synthesis in human cells, consistent with a role for DNA topoisomerase II (its target enzyme) at a late stage in replication. Fostriecin does not inhibit UV-induced excision repair. The less specific inhibitor novobiocin blocks repair in permeabilised cells given a low dose of UV, presumably through a mechanism other than the inhibition of topoisomerase II. Its effect cannot be accounted for by a depletion of the ATP required for incision. Camptothecin, an inhibitor of DNA topoisomerase I, blocks replicative DNA synthesis immediately but incompletely, suggesting a participation of topoisomerase I at the replication fork, but it, too, has no influence on DNA repair. We thus find no evidence for involvement of either topoisomerase I or II in the response of cells to UV damage.
Gedik
C M
CM
University of Aberdeen, Department of Biochemistry, Marischal College, UK.
Collins
A R
AR
D000475:Alkenes / Q000494:pharmacology; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D002166:Camptothecin / Q000494:pharmacology*; D002463:Cell Membrane Permeability; D004249:DNA Damage; D004260:DNA Repair / Q000187:drug effects*; D004261:DNA Replication / Q000187:drug effects*; D004273:DNA, Neoplasm / Q000528:radiation effects; D006367:HeLa Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D009675:Novobiocin / Q000494:pharmacology*; D011090:Polyenes; D011753:Pyrones; D059004:Topoisomerase I Inhibitors; D059005:Topoisomerase II Inhibitors; D014466:Ultraviolet Rays
D000475:Alkenes; D000903:Antibiotics, Antineoplastic; D004273:DNA, Neoplasm; D011090:Polyenes; D011753:Pyrones; D059004:Topoisomerase I Inhibitors; D059005:Topoisomerase II Inhibitors; D009675:Novobiocin; D002166:Camptothecin; C040313:fostriecin