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dc.contributor.authorMartín, Beatriz-
dc.contributor.authorVaquero, Alejandro-
dc.contributor.authorPriebe, Waldemar-
dc.contributor.authorPortugal, José-
dc.identifier.citationNucleic Acids Research 27(17): 3402-3409 (1999)es_ES
dc.description8 pages, 8 figures, 1 table.-- PMID: 10446226 [PubMed].-- PMCID: PMC148580.es_ES
dc.description.abstractAn in vitro transcription assay was used to compare the capacity of the bisintercalating anthracycline WP631 (which displays a remarkably high DNA-binding affinity) and the monointercalating anthracycline daunomycin to inhibit transcription initiation of the adenovirus major late promoter linked to a G-less transcribed DNA template. Both drugs inhibit basal RNA synthesis in a concentration-dependent way, and the drug concentrations required to inhibit transcription initiation are similar. However, in this study WP631 was around 15 times more efficient at inhibiting transcription initiation when used with an adenovirus promoter containing an upstream Sp1-protein binding site under experimental conditions in which the Sp1 protein acted as a transactivator in vitro. The differences in the ability of each drug to inhibit transcription initiation were related to the competition between Sp1 and the drugs for the same binding site. Concentrations of WP631 as low as 60 nM could inhibit the Sp1-activated transcription initiation in vitro. In contrast, the concentration of daunomycin required to inhibit Sp1-activated transcription by 50% was almost the same as the concentration required to inhibit basal transcription. The efficiency of WP631 at displacing Sp1 from its putative binding site was confirmed using gel retardation and footprinting assays. These results are the first unequivocal example of a direct effect of an intercalator on activated transcription initiation.es_ES
dc.description.sponsorshipThis work was financed by grants from the Spanish DGES (PB 95-0064 and PB 96-812) to J.P. and Texas Higher Education Coordinating Board (ATP#000015-090) to W.P. The support of the Generalitat de Catalunya through its ‘Centre de Referencia en Biotecnologia’ is also acknowledgedes_ES
dc.publisherOxford University Presses_ES
dc.titleBisanthracycline WP631 inhibits basal and Sp1-activated transcription initiation in vitroes_ES
dc.description.peerreviewedPeer reviewedes_ES
dc.contributor.funderMinisterio de Educación y Cultura (España)-
dc.contributor.funderTexas Higher Education Coordinating Board-
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