Transcription factor II H
|general transcription factor IIH, polypeptide 1, 62kDa|
|Locus||Chr. 11 p15.1-p14|
|general transcription factor IIH, polypeptide 2, 44kDa|
|Alt. symbols||BTF2, TFIIH, BTF2P44, T-BTF2P44|
|Locus||Chr. 5 q12.2-13.3|
|general transcription factor IIH, polypeptide 3, 34kDa|
|Alt. symbols||BTF2, TFIIH|
|Locus||Chr. 12 q24.31|
Transcription factor II Human (TFIIH) is one of several general transcription factors that make up the RNA polymerase II preinitiation complex. TFIIH consists of ten subunits, 7 of which (XPD, XPB, p62, p52, p44, p34 and TTDA) form the core complex. The cyclin activating kinase-subcomplex (CDK7, MAT1, and cyclin H) is linked to the core via the XPD protein Two of the subunits, ERCC2/XPD and ERCC3/XPB, have helicase and ATPase activities and help create the transcription bubble. In a test tube these subunits are only required for transcription if the DNA template is not already denatured or if it is supercoiled.
Two other TFIIH subunits, CDK7 and cyclin H, phosphorylate serine amino acids on the RNA polymerase II C-terminal domain and possibly other proteins involved in the cell cycle. Next to a vital function in transcription initiation, TFIIH is also involved in nucleotide excision repair.
It is responsible for giving the 'go' signal which is why it is assembled last.
Mutation in genes ERCC3/XPB, ERCC2/XPD or TTDA cause trichothiodystrophy, a condition characterized by photosensitivity, ichthyosis, brittle hair and nails, intellectual impairment, decreased fertility and/or short stature.
TFIIH participates in nucleotide excision repair (NER) by opening the DNA double helix after damage is initially recognized. NER is a multi-step pathway that removes a wide range of different damages that distort normal base pairing, including bulky chemical damages and UV-induced damages. Individuals with mutational defects in genes specifying protein components that catalyze the NER pathway, including the TFIIH components, often display features of premature aging (see DNA damage theory of aging).
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- Edifizi D, Schumacher B (2015). "Genome Instability in Development and Aging: Insights from Nucleotide Excision Repair in Humans, Mice, and Worms". Biomolecules. 5 (3): 1855–69. doi:10.3390/biom5031855. PMC . PMID 26287260.
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