Architecture of the Human and Yeast General Transcription and DNA Repair Factor TFIIH
Copyright policy )Architecture of the Human and Yeast General Transcription and DNA Repair Factor TFIIH
TFIIH is essential for both RNA polymerase II transcription and DNA repair, and mutations in TFIIH can result in human disease. Here, we determine the molecular architecture of human and yeast TFIIH by an integrative approach using chemical crosslinking/mass spectrometry (CXMS) data, biochemical analyses, and previously published electron microscopy maps. We identified four new conserved "topological regions" that function as hubs for TFIIH assembly and more than 35 conserved topological features within TFIIH, illuminating a network of interactions involved in TFIIH assembly and regulation of its activities. We show that one of these conserved regions, the p62/Tfb1 Anchor region, directly interacts with the DNA helicase subunit XPD/Rad3 in native TFIIH and is required for the integrity and function of TFIIH. We also reveal the structural basis for defects in patients with xeroderma pigmentosum and trichothiodystrophy, with mutations found at the interface between the p62 Anchor region and the XPD subunit.
- University of Colorado System United States
- Fred Hutchinson Cancer Research Center United States
- University of California, San Francisco United States
- University of Colorado Boulder United States
- Institut Pasteur France
Models, Molecular, Biomedical and clinical sciences, Saccharomyces cerevisiae Proteins, 572, DNA Repair, Transcription, Genetic, 1.1 Normal biological development and functioning, Bioinformatics and Computational Biology, 610, Saccharomyces cerevisiae, Medical and Health Sciences, Mass Spectrometry, Transcription Factors, TFII, Genetic, Models, Genetics, Humans, Protein Interaction Domains and Motifs, Molecular Biology, Xeroderma Pigmentosum Group D Protein, Xeroderma Pigmentosum, TFII, DNA Helicases, Molecular, Health sciences, Cell Biology, Biological Sciences, Biological sciences, Protein Subunits, Cross-Linking Reagents, Mutation, Generic health relevance, Transcription, Transcription Factor TFIIH, Transcription Factors, Developmental Biology
Models, Molecular, Biomedical and clinical sciences, Saccharomyces cerevisiae Proteins, 572, DNA Repair, Transcription, Genetic, 1.1 Normal biological development and functioning, Bioinformatics and Computational Biology, 610, Saccharomyces cerevisiae, Medical and Health Sciences, Mass Spectrometry, Transcription Factors, TFII, Genetic, Models, Genetics, Humans, Protein Interaction Domains and Motifs, Molecular Biology, Xeroderma Pigmentosum Group D Protein, Xeroderma Pigmentosum, TFII, DNA Helicases, Molecular, Health sciences, Cell Biology, Biological Sciences, Biological sciences, Protein Subunits, Cross-Linking Reagents, Mutation, Generic health relevance, Transcription, Transcription Factor TFIIH, Transcription Factors, Developmental Biology
citations This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).89 popularity This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.Top 10% influence This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).Top 10% impulse This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.Top 1%
Citations provided by BIP!Popularity provided by BIP!