Camptothecin inhibits hsp 70 heat-shock transcription and induces DNA strand breaks in hsp 70 genes in Drosophila.
Camptothecin is a cytotoxic drug which inhibits cellular nucleic acid synthesis. Associated with this inhibition is the induction of protein-linked DNA strand breaks. Recent studies have demonstrated that camptothecin interferes with the DNA breakage and rejoining activity of the enzyme DNA topoisomerase I and stabilizes a cleavable complex between this enzyme and DNA. Treatment of this complex with a protein denaturant results in DNA strand breaks and the covalent attachment of topoisomerase to the 3'-end of the DNA breaks. In this paper we have mapped the camptothecin-induced DNA breaks on the hsp 70 heat-shock gene in cultured Drosophila cells. Drug-induced breaks are present primarily within the coding region of this gene and occur only when transcription of this gene is activated by heat. Camptothecin (20 microM) was also observed to inhibit heat-induced hsp 70 transcription greater than 70%. The possible role of topoisomerase I in hsp 70 heat-shock gene transcription is discussed.
Rowe
T C
TC
Couto
E
E
Kroll
D J
DJ
D000818:Animals; D002166:Camptothecin / Q000494:pharmacology*; D002478:Cells, Cultured; D004247:DNA / Q000187:drug effects*; D004264:DNA Topoisomerases, Type I / Q000378:metabolism; D004330:Drosophila; D005786:Gene Expression Regulation / Q000187:drug effects; D005796:Genes / Q000187:drug effects*; D006360:Heat-Shock Proteins / Q000235:genetics*; D014158:Transcription, Genetic / Q000187:drug effects*
D006360:Heat-Shock Proteins; D004247:DNA; D004264:DNA Topoisomerases, Type I; D002166:Camptothecin