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 topolsomerase I, biocks 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. © 1990 Oxford University Press.