Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0043346 (xeroderma pigmentosum)
 2,924 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Transcription factor IIH (TFIIH) is involved both in transcription initiation by RNA polymerase II and in nucleotide excision-repair. Nucleotide excision-repair occurs at higher rates in transcriptionally active regions of the genome. Genetic studies indicate that this transcription-coupled repair is dependent on the Cockayne syndrome group A and B proteins, as well as TFIIH subunits. Previous work indicated that Cockayne syndrome group B interacts with RNA polymerase II molecules engaged in ternary complexes containing DNA and RNA. Evidence presented here indicates that this complex can interact with a factor containing the TFIIH core subunits p62 and xeroderma pigmentosum subunit B/excision repair cross-complementing 3. The targeting of TFIIH or a TFIIH-like repair factor to transcriptionally active DNA indicates a potential mechanism for transcription-coupled repair in human cells.
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PMID:RNA polymerase II elongation complexes containing the Cockayne syndrome group B protein interact with a molecular complex containing the transcription factor IIH components xeroderma pigmentosum B and p62. 977 88

Transcription factor IIH (TFIIH) is eukaryotic multi protein complex identified in early 90's. Subsequent years have shown exceptional conservation of its structure from yeast to human. Although initially considered to be exclusively a basal transcription factor responsible for initiation of transcription and transition from initiation to elongation, TFIIH is also important in nucleotide excision repair for opening DNA at the site of a lesion and for recruitment of additional repair factors. Recently it was suggested that intact holocomplex of TFIIH is required for cell cycle regulation. Moreover, mutations in TFIIH subunits lead to three distinct genetic disorders: xeroderma pigmentosum (DNA repair disorder/cancer syndrome), Cockayne syndrome (DNA repair disorder/transcription syndrome/segmental progeria) and trichothiodystrophy (DNA repair disorder/transcription syndrome). This review is focused on the TFIIH structure, its role in transcription, DNA repair and cell cycle regulation and association with some human hereditary disorders.
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PMID:Transcription factor IIH - the protein complex with multiple functions. 2042 18

Transcription factor IIH (TFIIH) is a multiprotein complex involved in both eukaryotic transcription and DNA repair, revealing a tight connection between these two processes. Composed of 10 subunits, it can be resolved into a 7-subunits core complex with the XPB translocase and the XPD helicase, and the 3-subunits kinase complex CAK, which also exists as a free complex with a distinct function. Initially identified as basal transcription factor, TFIIH also participates in transcription regulation and plays a key role in nucleotide excision repair (NER) for opening DNA at damaged sites, lesion verification and recruitment of additional repair factors. Our understanding of TFIIH function in eukaryotic cells has greatly benefited from studies of the genetic rare diseases xeroderma pigmentosum (XP), Cockayne syndrome (CS) and trichothiodystrophy (TTD), that are not only characterized by cancer and aging predispositions but also by neurological and developmental defects. Although much remains unknown about TFIIH function, significant progresses have been done regarding the structure of the complex, the functions of its catalytic subunits and the multiple roles of the regulatory core-TFIIH subunits. This review provides a non-exhaustive survey of key discoveries on the structure and function of this pivotal factor, which can be considered as a promising target for therapeutic strategies.
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PMID:TFIIH: A multi-subunit complex at the cross-roads of transcription and DNA repair. 3079 33