| 词条 | Transcription factor II H |
| 释义 |
|Name= general transcription factor IIH, polypeptide 1, 62kDa |caption= |image= |width= |HGNCid=4655 |Symbol=GTF2H1 |AltSymbols= BTF2 |EntrezGene=2965 |OMIM=189972 |RefSeq=NM_005316 |UniProt=P32780 |PDB= |ECnumber= |Chromosome=11 |Arm=p |Band=15.1 |LocusSupplementaryData=-p14 }}{{infobox protein |Name=general transcription factor IIH, polypeptide 2, 44kDa |caption= |image= |width= |HGNCid=4656 |Symbol=GTF2H2 |AltSymbols=BTF2, TFIIH, BTF2P44, T-BTF2P44 |EntrezGene=2966 |OMIM=601748 |RefSeq=NM_001515 |UniProt=Q13888 |PDB= |ECnumber= |Chromosome=5 |Arm=q |Band=12.2 |LocusSupplementaryData=-13.3 }}{{infobox protein |Name=general transcription factor IIH, polypeptide 3, 34kDa |caption= |image= |width= |HGNCid=4657 |Symbol=GTF2H3 |AltSymbols=BTF2, TFIIH |EntrezGene=2967 |OMIM=601750 |RefSeq=NM_001516 |UniProt=Q13889 |PDB= |ECnumber= |Chromosome=12 |Arm=q |Band=24.31 |LocusSupplementaryData= }}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.[1][2] 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[3] 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 TFIIHBefore 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.[4] Structure of TFIIHThe 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.[5] FunctionsGeneral 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.[7][8] Also, the purified TFIIH has role in making RNA by activating enzyme a-amanitin. TrichothiodystrophyMutation 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.[9] DiseaseGenetic 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.[10] In addition to genetic variations, virus-encoded proteins also target TFIIH.[11] DNA repairTFIIH 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[9][12] (see DNA damage theory of aging). Mechanism of TFIIH repairing DNA damaged sequenceReferences1. ^{{cite journal | vauthors = Flores O, Lu H, Reinberg D | title = Factors involved in specific transcription by mammalian RNA polymerase II. Identification and characterization of factor IIH | journal = The Journal of Biological Chemistry | volume = 267 | issue = 4 | pages = 2786–93 | date = February 1992 | pmid = 1733973 }} 2. ^{{cite journal | vauthors = Kim TK, Ebright RH, Reinberg D | title = Mechanism of ATP-dependent promoter melting by transcription factor IIH | journal = Science | volume = 288 | issue = 5470 | pages = 1418–22 | date = May 2000 | pmid = 10827951 | doi = 10.1126/science.288.5470.1418 | author2-link = Richard H. Ebright | bibcode = 2000Sci...288.1418K }} 3. ^{{cite journal | vauthors = Lee TI, Young RA | title = Transcription of eukaryotic protein-coding genes | journal = Annual Review of Genetics | volume = 34 | issue = | pages = 77–137 | year = 2000 | pmid = 11092823 | doi = 10.1146/annurev.genet.34.1.77 }} 4. ^{{cite journal | vauthors = Rimel JK, Taatjes DJ | title = The essential and multifunctional TFIIH complex | journal = Protein Science | volume = 27 | issue = 6 | pages = 1018–1037 | date = June 2018 | pmid = 29664212 | doi = 10.1002/pro.3424 }} 5. ^{{cite journal | vauthors = Drapkin R, Reardon JT, Ansari A, Huang JC, Zawel L, Ahn K, Sancar A, Reinberg D | title = Dual role of TFIIH in DNA excision repair and in transcription by RNA polymerase II | journal = Nature | volume = 368 | issue = 6473 | pages = 769–72 | date = April 1994 | pmid = 8152490 | doi = 10.1038/368769a0 }} 6. ^1 {{cite journal | vauthors = Compe E, Egly JM | title = TFIIH: when transcription met DNA repair | journal = Nature Reviews. Molecular Cell Biology | volume = 13 | issue = 6 | pages = 343–54 | date = May 2012 | pmid = 22572993 | doi = 10.1038/nrm3350 }} 7. ^{{cite journal | vauthors = Hoogstraten D, Nigg AL, Heath H, Mullenders LH, van Driel R, Hoeijmakers JH, Vermeulen W, Houtsmuller AB | title = Rapid switching of TFIIH between RNA polymerase I and II transcription and DNA repair in vivo | journal = Molecular Cell | volume = 10 | issue = 5 | pages = 1163–74 | date = November 2002 | pmid = 12453423 | doi = 10.1016/s1097-2765(02)00709-8 }} 8. ^{{cite journal | vauthors = Assfalg R, Lebedev A, Gonzalez OG, Schelling A, Koch S, Iben S | title = TFIIH is an elongation factor of RNA polymerase I | journal = Nucleic Acids Research | volume = 40 | issue = 2 | pages = 650–9 | date = January 2012 | pmid = 21965540 | doi = 10.1093/nar/gkr746 }} 9. ^1 {{cite journal | vauthors = Theil AF, Hoeijmakers JH, Vermeulen W | title = TTDA: big impact of a small protein | journal = Experimental Cell Research | volume = 329 | issue = 1 | pages = 61–8 | date = November 2014 | pmid = 25016283 | doi = 10.1016/j.yexcr.2014.07.008 }} 10. ^{{cite journal | vauthors = 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 | title = Phenotypic heterogeneity in the XPB DNA helicase gene (ERCC3): xeroderma pigmentosum without and with Cockayne syndrome | journal = Human Mutation | volume = 27 | issue = 11 | pages = 1092–103 | date = November 2006 | pmid = 16947863 | doi = 10.1002/humu.20392 }} 11. ^{{cite journal | vauthors = Le May N, Dubaele S, Proietti De Santis L, Billecocq A, Bouloy M, Egly JM | title = TFIIH transcription factor, a target for the Rift Valley hemorrhagic fever virus | journal = Cell | volume = 116 | issue = 4 | pages = 541–50 | date = February 2004 | pmid = 14980221 | doi = 10.1016/s0092-8674(04)00132-1 }} 12. ^{{cite journal | vauthors = Edifizi D, Schumacher B | title = Genome Instability in Development and Aging: Insights from Nucleotide Excision Repair in Humans, Mice, and Worms | journal = Biomolecules | volume = 5 | issue = 3 | pages = 1855–69 | date = August 2015 | pmid = 26287260 | pmc = 4598778 | doi = 10.3390/biom5031855 }} External links
2 : Gene expression|Transcription factors |
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