Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.7.6 (RNA polymerase)
 34,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The requirement for ATP hydrolysis in the initiation of RNA polymerase II (Pol II)-directed transcription and the relationship between ATP and novobiocin action led us to investigate whether novobiocin could inhibit transcription of the mouse metallothionein-I (MT-I) gene. Novobiocin inhibited the MT-I gene transcription in a fractionated rat hepatoma nuclear extract in a dose-dependent manner by direct interaction with a nuclear factor(s). This interaction prevented formation of stable preinitiation complexes but did not affect elongation of MT-I mRNA. Preincubation of the nuclear extract with ATP prevented the action of novobiocin on MT-I gene transcription. Although novobiocin is known to inhibit DNA topoisomerase II, VM-26, a specific inhibitor of this enzyme had no effect on the transcription. These results indicate that novobiocin blocks the Pol II-directed transcription by inhibiting formation of preinitiation complexes at an ATP-dependent step.
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PMID:Novobiocin inhibits initiation of RNA polymerase II-directed transcription of the mouse metallothionein-I gene independent of its effect on DNA topoisomerase II. 282 31

Novobiocin concentrations normally used to inhibit a putative eukaryotic DNA gyrase have been found to inhibit transcription of a yeast 5S rRNA gene using an in vitro yeast transcription system. Purified RNA polymerase III and three yeast transcription factors (chromatographically separated, partially purified and free of any detectable gyrase activity) were used. Novobiocin prevents specific transcription if added to the in vitro system immediately prior to the addition of transcription factors and RNA polymerase. If a stable transcription factor complex is allowed to form prior to the addition of novobiocin, concentrations of novobiocin as high as 1000 micrograms/ml have no effect on in vitro transcription. Transcription factors TFIIIA and TFIIIC are able to be stably sequestered onto 5SrDNA-cellulose, but factor TFIIIB is not able to associate with the 5SrDNA-TFIIIA-TFIIIC complex in the presence of novobiocin. Although novobiocin is able to precipitate other basic proteins, it does not appear to precipitate any of these class III gene transcription factors, but instead appears to act by disrupting specific factor-factor interactions.
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PMID:Novobiocin inhibits interactions required for yeast TFIIIB sequestration during stable transcription complex formation in vitro. 354 36

Coumermycin A1, a Novobiocin related antibiotic, has been tested in vivo and in vitro for its activity on Influenza A viruses. In a range of concentrations between 3 and 5 micrograms/ml virus production was drastically reduced. The drug was able to inhibit virus release into culture medium also if added up to the sixth hour following infection and its action was reversible within this time. The synthesis of virus induced polypeptides was generally depressed but production of the HA was more deeply inhibited. Viral transcriptase activity in vitro was also affected by the presence of Coumermycin A1 but at doses which seem to high to consider this event as a phenomenon likely to play a role in vivo. It is suggested that the antiviral activity of the drug is mediated by the inhibition of the host cell metabolism.
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PMID:Effect of coumermycin on influenza A virus replicative cycle. 654 62

Phage P4 DNA is replicated in cell-free extracts of Escherichia coli in the presence of partially purified P4 alpha protein [Krevolin and Calendar (1985), J. Mol. Biol. 182, 507-517]. Using a modified in vitro replication assay, we have further characterized this process. Analysis by agarose gel electrophoresis and autoradiography of in vitro replicated molecules demonstrates that the system yields supercoiled monomeric DNA as the main product. Electron microscopic analysis of in vitro generated intermediates indicates that DNA synthesis initiates in vitro mainly at ori, the origin of replication used in vivo. Replication proceeds from this origin bidirectionally, resulting in theta-type molecules. In contrast to the in vivo situation, no extensive single-stranded regions were found in these intermediates. The initiation proteins of the host, DnaB and DnaG, and the chaperones DnaJ and DnaK are not required for P4 replication, because polyclonal antibodies against those polypeptides do not inhibit the process. The reaction is inhibited by antibodies against the SSB protein, and by ara-CTP, a specific inhibitor of DNA polymerase III holoenzyme. Consistent with previous reports, P4 in vitro replication is independent of transcription by host RNA polymerase. Novobiocin, a DNA gyrase inhibitor, strongly inhibits P4 DNA synthesis, indicating that form I DNA is the required substrate.
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PMID:Phage P4 DNA replication in vitro. 802 13