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Nucleic Acids Research, 1990, Vol. 18, No. 4 1007-1013
© 1990

MOLECULAR BIOLOGY

Comparison of effects of fostriecin, novobiocin, and camptothecin, inhibitors of DNA topoisomerases, on DNA replication and repair in human cells

Catherine M. Gedik and Andrew R. Collins

University of Aberdeen, Department of Biochemistry Marischal College, Aberdeen AB9 1AS, UK

Received September 13, 1989. Revised December 5, 1989. Accepted December 5, 1989.

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.


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