Identification of TFB5, a new component of general transcription and DNA repair factor IIH.
We previously described the use of quantitative proteomics to study macromolecular complexes. Applying the method to analyze a yeast RNA polymerase II preinitiation complex, we identified a new 8-kDa protein, encoded by the uncharacterized open reading frame YDR079c-a, as a potential new component of the preinitiation complex. Here we show ... that YDR079c-a is a bona fide component of polymerase II preinitiation complexes and investigate its role in transcription. YDR079c-a is recruited to promoters both in vivo and in vitro and is required for efficient transcription in vitro and for normal induction of GAL genes. In addition, YDR079c-a is a core component of general transcription and DNA repair factor IIH and is required for efficient recruitment of TFIIH to a promoter. Yeast lacking YDR079c-a grow slowly, and, like strains carrying mutations in core TFIIH subunits, are sensitive to ultraviolet radiation. YDR079c-a is conserved throughout evolution, and mutations in the human ortholog account for a DNA repair-deficient form of the tricothiodystrophy disorder called TTD-A(2). The identification of a new, evolutionarily conserved, core TFIIH subunit is essential for our understanding of TFIIH function in transcription, DNA repair and human disease.
Mesh Terms:
DNA Polymerase II, DNA Repair, Plasmids, Saccharomyces cerevisiae, Transcription Factor TFIIH, Transcription Factors, TFII, Transcription, Genetic
DNA Polymerase II, DNA Repair, Plasmids, Saccharomyces cerevisiae, Transcription Factor TFIIH, Transcription Factors, TFII, Transcription, Genetic
Nat. Genet.
Date: Jul. 01, 2004
PubMed ID: 15220919
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