ArticleNature communications2023
Dynamic conformational switching underlies TFIIH function in transcription and DNA repair and impacts genetic diseases.
Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 22 citations in OpenAlex.
- UV damage mapping reveals different impacts of yeast XPD mutations on global genomic and transcription-coupled DNA repair.The Journal of biological chemistry · 2026Article
- Article
- Integrating Structural, Biochemical, and Cellular Perspectives on the TFIIH Helicases XPB and XPD.Biomolecules · 2026Review
- Mechanisms of transcription-coupled repair and DNA damage surveillance in health and disease.Nature reviews. Molecular cell biology · 2026Review
- An efficient computational chemistry approach to generating negative data for drug discovery pipeline validation.Frontiers in bioinformatics · 2026Article
- Translocation mechanism of xeroderma pigmentosum group D protein on single-stranded DNA and genetic disease etiology.Nature communications · 2025Article
- Trichothiodystrophy-causative pathogenic variants impair a cooperative action of TFIIH and DDX1 in R-loop processing.Nucleic acids research · 2025Article
- RNA sculpting by the primordial Helix-clasp-Helix-Strand-Loop (HcH-SL) motif enforces chemical recognition enabling diverse KH domain functions.The Journal of biological chemistry · 2025Review
- Novel role of general transcript factor IIH subunit 2 (GTF2H2) in the development and sex disparity of hepatocellular carcinoma.Oncogene · 2025Article
- Molecular model of TFIIH recruitment to the transcription-coupled repair machinery.Nature communications · 2025Article
- Molecular architecture and functional dynamics of the pre-incision complex in nucleotide excision repair.Nature communications · 2024Article
- Glyoxal oxidase-mediated detoxification of reactive carbonyl species contributes to virulence, stress tolerance, and development in a pathogenic fungus.PLoS pathogens · 2024Article
- A goldilocks computational protocol for inhibitor discovery targeting DNA damage responses including replication-repair functions.Frontiers in molecular biosciences · 2024Article
- Differing structures and dynamics of two photolesions portray verification differences by the human XPD helicase.Nucleic acids research · 2023Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
Transcription factor IIH (TFIIH) is a protein assembly essential for transcription initiation and nucleotide excision repair (NER). Yet, understanding of the conformational switching underpinning these diverse TFIIH functions remains fragmentary. TFIIH mechanisms critically depend on two translocase subunits, XPB and XPD. To unravel their functions and regulation, we build cryo-EM based TFIIH models in transcription- and NER-competent states. Using simulations and graph-theoretical analysis methods, we reveal TFIIH's global motions, define TFIIH partitioning into dynamic communities and show how TFIIH reshapes itself and self-regulates depending on functional context. Our study uncovers an internal regulatory mechanism that switches XPB and XPD activities making them mutually exclusive between NER and transcription initiation. By sequentially coordinating the XPB and XPD DNA-unwinding activities, the switch ensures precise DNA incision in NER. Mapping TFIIH disease mutations onto network models reveals clustering into distinct mechanistic classes, affecting translocase functions, protein interactions and interface dynamics.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.