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Cell. 1990 Jan 12;60(1):141-9.

Rapid induction of c-fos transcription reveals quantitative linkage of RNA polymerase II and DNA topoisomerase I enzyme activities.

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Institut für Zell-und Tumorbiologie, Deutsches Krebsforschungszentrum im Neuenheimer Feld 280, Heidelberg, Federal Republic of Germany.


The functional association between DNA topoisomerase I and gene activity has been analyzed using the tightly regulated c-fos proto-oncogene, which undergoes rapid transitions between active and inactive states of transcription. We show that the topoisomerase I inhibitor camptothecin can be used to measure topoisomerase I activity throughout the transcription cycle of the c-fos gene. Upon induction of c-fos transcription in the presence of camptothecin, topoisomerase I cleavages spread through the gene in the 5' to 3' direction and concomitantly transcriptional elongation is retarded. Parallel kinetic measurements of RNA polymerase II activity and topoisomerase I activity demonstrate a quantitative and temporal link between the two enzymes. Our results argue that topoisomerase I quantitatively relieves the torsional consequences of transcriptional elongation in intact cells.

[Indexed for MEDLINE]

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