| Abstract: |
The process of gene transcription requires the recruitment of a hypophosphorylated form of RNA polymerase II (Pol II) to a gene promoter. The TFIIH-associated kinase Cdk7/Kin28 hyperphosphorylates the promoter-bound polymerase; this event is thought to play a crucial role in transcription initiation and promoter clearance. Studies using temperature-sensitive mutants of Kin28 have provided the most compelling evidence for an essential role of its kinase activity in global mRNA synthesis. In contrast, using a small molecule inhibitor that specifically inhibits Kin28 in vivo, we find that the kinase activity is not essential for global transcription. Unlike the temperature-sensitive alleles, the small-molecule inhibitor does not perturb protein-protein interactions nor does it provoke the disassociation of TFIIH from gene promoters. These results lead us to conclude that other functions of TFIIH, rather than the kinase activity, are critical for global gene transcription. © 2007 by The National Academy of Sciences of the USA. |
| Keywords: |
unclassified drug; promoter region; genetics; mutation; comparative study; metabolism; actin; allele; atp-binding cassette transporters; enzyme inhibition; protein protein interaction; alleles; genetic transcription; in vivo study; transcription, genetic; enzyme activation; drug effect; enzymology; enzyme activity; phosphorylation; gene expression regulation; biosynthesis; drug antagonism; enzyme phosphorylation; kinetics; messenger rna; saccharomyces cerevisiae; rna, messenger; abc transporter; chemical genetics; saccharomyces cerevisiae proteins; saccharomyces cerevisiae protein; actins; cyclin-dependent kinases; cyclin dependent kinase; rna polymerase ii; fungal protein; gene expression regulation, fungal; enzyme induction; rna, fungal; cyclin dependent kinase 7; phosphoprotein phosphatase; transcription factor iih; transcription factor tfiih; fungal proteins; heat; temperature sensitive mutant; ctd kinase; tfiih disassembly; act1 protein, s cerevisiae; fungal rna; kin28 protein kinase, s cerevisiae; pdr5 protein, s cerevisiae; messenger rna synthesis
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