期刊
MOLECULAR CELL
卷 59, 期 5, 页码 794-806出版社
CELL PRESS
DOI: 10.1016/j.molcel.2015.07.016
关键词
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资金
- NIH [P50 GM076547, R21CA175849, RO1 GM053451, P41 GM109824, R01 GM083960]
- National Science Foundation (NSF) [MCB 1244175]
- Howard Hughes Medical Institute
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.
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