DNA-dependent protein kinase specifically represses promoter-directed transcription initiation by RNA polymerase I.
DNA-dependent protein kinase (DNA-PK) is a nuclear enzyme that phosphorylates several transcription factors, but its cellular function has not been elucidated. Here I show that DNA-PK strongly inhibits promoter-directed transcription initiation by Xenopus RNA polymerase I in vitro. The repression is due to protein phosphorylation, since it is relieved by 6-dimethylaminopurine, an inhibitor of protein kinases. DNA-PK inhibits transcription from both linear and circular templates, but the repression is more efficient on linear templates. DNA-PK has no effect on promoter-directed transcription by RNA polymerases II and III. Partial fractionation of the in vitro transcription system shows that a protein fraction containing transcription factor Rib1, the Xenopus equivalent of human SL1, mediates the repression of transcription by DNA-PK. The present data suggest a role for DNA-PK in down-regulating ribosomal gene transcription.
Labhart
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Department of Molecular and Experimental Medicine, Scripps Research Institute, La Jolla, CA 92037, USA.
D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D002460:Cell Line; D051747:DNA-Activated Protein Kinase; D004268:DNA-Binding Proteins / Q000378:metabolism; D015870:Gene Expression; D006367:HeLa Cells; D006801:Humans; D009687:Nuclear Proteins; D035463:Pol1 Transcription Initiation Complex Proteins; D011401:Promoter Regions, Genetic; D047428:Protein Kinase Inhibitors; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D012318:RNA Polymerase I / Q000378:metabolism*; D012270:Ribosomes / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic; D029867:Xenopus Proteins; D014982:Xenopus laevis
D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D035463:Pol1 Transcription Initiation Complex Proteins; D047428:Protein Kinase Inhibitors; C092979:Rib1 protein, Xenopus; D014157:Transcription Factors; D029867:Xenopus Proteins; C063660:transcription initiation factor TIF-IB; C001020:N(6),N(6)-dimethyladenine; D051747:DNA-Activated Protein Kinase; C497263:PRKDC protein, human; D017346:Protein Serine-Threonine Kinases; D012318:RNA Polymerase I; D000225:Adenine