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 (Transcription Factor II H; TFIIH) is an important protein complex, having roles in transcription of various protein-coding genes and DNA nucleotide excision repair (NER) pathways. TFIIH first came to light in 1989 when general transcription factor-δ or basic transcription factor 2 was characterized as an indispensable transcription factor in vitro. This factor was also isolated from yeast and finally named as TFIIH in 1992.
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.
TFIIH is a general transcription factor that acts to recruit RNA Pol II to the promoters of genes. It functions as a helicase that unwinds DNA. It also unwinds DNA after a DNA lesion has been recognized by either the global genome repair (GGR) pathway or the transcription-coupled repair (TCR) pathway of NER.
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.
Genetic polymorphisms of genes that encode subunits of TFIIH are known to be associated with increased cancer susceptibility in many tissues, e.g.; skin tissue, breast tissue and lung tissue. Mutations in the subunits (such as XPD and XPB) can lead to a variety of diseases, including xeroderma pigmentosum (XP) or XP combined with Cockayne syndrome. In addition to genetic variations, virus-encoded proteins also target TFIIH.
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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- Theil AF, Hoeijmakers JH, Vermeulen W (November 2014). "TTDA: big impact of a small protein". Experimental Cell Research. 329 (1): 61–8. doi:10.1016/j.yexcr.2014.07.008. PMID 25016283.
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- Le May N, Dubaele S, Proietti De Santis L, Billecocq A, Bouloy M, Egly JM (February 2004). "TFIIH transcription factor, a target for the Rift Valley hemorrhagic fever virus". Cell. 116 (4): 541–50. doi:10.1016/s0092-8674(04)00132-1. PMID 14980221.
- Edifizi D, Schumacher B (August 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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