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 (ERCC2/XPD, ERCC3/XPB, GTF2H1/p62, GTF2H4/p52, GTF2H2/p44, GTF2H3/p34 and GTF2H5/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.
The History of TFIIH
Before TFIIH identified it has a several names : this factor first in 1989 isolated from liver of rat known that time as factor transcription delta it also, isolated from cancer cell known that time as Basic transcription factor 2, Also, it is isolated from yeast known transcription factor B. Finally, in 1992 known as TFIIH.
Structure of TFIIH
The TFIIH contains of two main pieces the core with is the core XPB has these subunits p62, p52, p44, p34 and p8 and CAK composed of CDK7, cyclin H and MAT1. The unit that join the core to the CAK called XPD.
General function of TFIIH:
(NER)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. Also, the purified TFIIH has role in making RNA by activating enzyme a-amanitin.
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).
Mechanism of TFIIH repairing DNA damaged sequence
- Flores O, Lu H, Reinberg D (February 1992). "Factors involved in specific transcription by mammalian RNA polymerase II. Identification and characterization of factor IIH". The Journal of Biological Chemistry. 267 (4): 2786–93. PMID 1733973.
- Kim TK, Ebright RH, Reinberg D (May 2000). "Mechanism of ATP-dependent promoter melting by transcription factor IIH". Science. 288 (5470): 1418–22. Bibcode:2000Sci...288.1418K. doi:10.1126/science.288.5470.1418. PMID 10827951.
- Lee TI, Young RA (2000). "Transcription of eukaryotic protein-coding genes". Annual Review of Genetics. 34: 77–137. doi:10.1146/annurev.genet.34.1.77. PMID 11092823.
- Rimel JK, Taatjes DJ (June 2018). "The essential and multifunctional TFIIH complex". Protein Science. 27 (6): 1018–1037. doi:10.1002/pro.3424. PMID 29664212.
- Drapkin R, Reardon JT, Ansari A, Huang JC, Zawel L, Ahn K, Sancar A, Reinberg D (April 1994). "Dual role of TFIIH in DNA excision repair and in transcription by RNA polymerase II". Nature. 368 (6473): 769–72. doi:10.1038/368769a0. PMID 8152490.
- Compe E, Egly JM (May 2012). "TFIIH: when transcription met DNA repair". Nature Reviews. Molecular Cell Biology. 13 (6): 343–54. doi:10.1038/nrm3350. PMID 22572993.
- Hoogstraten D, Nigg AL, Heath H, Mullenders LH, van Driel R, Hoeijmakers JH, Vermeulen W, Houtsmuller AB (November 2002). "Rapid switching of TFIIH between RNA polymerase I and II transcription and DNA repair in vivo". Molecular Cell. 10 (5): 1163–74. doi:10.1016/s1097-2765(02)00709-8. PMID 12453423.
- Assfalg R, Lebedev A, Gonzalez OG, Schelling A, Koch S, Iben S (January 2012). "TFIIH is an elongation factor of RNA polymerase I". Nucleic Acids Research. 40 (2): 650–9. doi:10.1093/nar/gkr746. PMID 21965540.
- 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.
- Oh KS, Khan SG, Jaspers NG, Raams A, Ueda T, Lehmann A, Friedmann PS, Emmert S, Gratchev A, Lachlan K, Lucassan A, Baker CC, Kraemer KH (November 2006). "Phenotypic heterogeneity in the XPB DNA helicase gene (ERCC3): xeroderma pigmentosum without and with Cockayne syndrome". Human Mutation. 27 (11): 1092–103. doi:10.1002/humu.20392. PMID 16947863.
- 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 4598778. PMID 26287260.
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