TATA binding protein-associated CK2 transduces DNA damage signals to the RNA polymerase III transcriptional machinery.
Here we report that RNA polymerase (pol) III transcription is repressed in response to DNA damage by downregulation of TFIIIB, the core component of the pol III transcriptional machinery. Protein kinase CK2 transduces this stress signal to TFIIIB. CK2 associates with and normally activates the TATA binding protein (TBP) subunit of TFIIIB. The beta regulatory subunit of CK2 binds to TBP and is required for high TBP-associated CK2 activity and pol III transcription in unstressed cells. Transcriptional repression induced by DNA damage requires CK2 and coincides with downregulation of TBP-associated CK2 and dissociation of catalytic subunits from TBP-CK2 complexes. Therefore, CK2 is the terminal effector in a signaling pathway that represses pol III transcription when genome integrity is compromised.
Ghavidel
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Department of Biochemistry, University of Alberta, Edmonton, Alberta, Canada T6G 2H7.
Schultz
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MC
D047390:Casein Kinase II; D004249:DNA Damage; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D017930:Genes, Reporter / Q000235:genetics; D015151:Immunoblotting; D046911:Macromolecular Substances; D008741:Methyl Methanesulfonate / Q000494:pharmacology; D009153:Mutagens / Q000494:pharmacology; D011233:Precipitin Tests; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D021122:Protein Subunits; D012320:RNA Polymerase III / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D035181:TATA-Box Binding Protein; D035361:Transcription Factor TFIIIB; D014157:Transcription Factors / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D014158:Transcription, Genetic / Q000502:physiology; D014466:Ultraviolet Rays; D015003:Yeasts / Q000235:genetics / Q000502:physiology
D004268:DNA-Binding Proteins; D046911:Macromolecular Substances; D009153:Mutagens; D021122:Protein Subunits; D011993:Recombinant Fusion Proteins; D035181:TATA-Box Binding Protein; D035361:Transcription Factor TFIIIB; D014157:Transcription Factors; D008741:Methyl Methanesulfonate; D047390:Casein Kinase II; D017346:Protein Serine-Threonine Kinases; D012320:RNA Polymerase III