transcription factor tfiih


Summary: A general transcription factor that is involved in basal GENETIC TRANSCRIPTION and NUCLEOTIDE EXCISION REPAIR. It consists of nine subunits including ATP-DEPENDENT DNA HELICASES; CYCLIN H; and XERODERMA PIGMENTOSUM GROUP D PROTEIN.

Top Publications

  1. Santagati F, Botta E, Stefanini M, Pedrini A. Different dynamics in nuclear entry of subunits of the repair/transcription factor TFIIH. Nucleic Acids Res. 2001;29:1574-81 pubmed
    ..These findings suggest that the nuclear entry of XPD depends on its complexation with other proteins in the cytoplasm, possibly other components of the TFIIH complex. ..
  2. Schultz P, Fribourg S, Poterszman A, Mallouh V, Moras D, Egly J. Molecular structure of human TFIIH. Cell. 2000;102:599-607 pubmed
    ..Within the ring structure, p44 was flanked on either side by the XPB and XPD helicases. These observations provide us with a quartenary organizational model of TFIIH. ..
  3. Chen D, Riedl T, Washbrook E, Pace P, Coombes R, Egly J, et al. Activation of estrogen receptor alpha by S118 phosphorylation involves a ligand-dependent interaction with TFIIH and participation of CDK7. Mol Cell. 2000;6:127-37 pubmed
    ..These findings are suggestive of a novel mechanism by which nuclear receptor activity can be regulated by ligand-dependent recruitment of modifying activities, such as kinases. ..
  4. Zhovmer A, Oksenych V, Coin F. Two sides of the same coin: TFIIH complexes in transcription and DNA repair. ScientificWorldJournal. 2010;10:633-43 pubmed publisher
    ..These data highlight the dynamic composition of a fundamental cellular factor that adapts its subunit composition to the cell needs. ..
  5. Liu J, Akoulitchev S, Weber A, Ge H, Chuikov S, Libutti D, et al. Defective interplay of activators and repressors with TFIH in xeroderma pigmentosum. Cell. 2001;104:353-63 pubmed
    ..Mutations in TFIIH that impair regulation by FBP and FIR affect proper regulation of c-myc expression and have implications in the development of malignancy. ..
  6. Vermeulen W, Bergmann E, Auriol J, Rademakers S, Frit P, Appeldoorn E, et al. Sublimiting concentration of TFIIH transcription/DNA repair factor causes TTD-A trichothiodystrophy disorder. Nat Genet. 2000;26:307-13 pubmed
    ..The reduction of TFIIH mainly affects its repair function and hardly influences transcription. ..
  7. Liu J, He L, Collins I, Ge H, Libutti D, Li J, et al. The FBP interacting repressor targets TFIIH to inhibit activated transcription. Mol Cell. 2000;5:331-41 pubmed
    ..Thus, FIR locks TFIIH in an activation-resistant configuration that still supports basal transcription. ..
  8. Zurita M, Merino C. The transcriptional complexity of the TFIIH complex. Trends Genet. 2003;19:578-84 pubmed
    ..The second suggests that mutations in TFIIH produce specific phenotypes arising from differential interactions of this complex with different transcription regulatory factors. ..
  9. de Laat W, Jaspers N, Hoeijmakers J. Molecular mechanism of nucleotide excision repair. Genes Dev. 1999;13:768-85 pubmed

More Information


  1. Ranish J, Hahn S, Lu Y, Yi E, Li X, Eng J, et al. Identification of TFB5, a new component of general transcription and DNA repair factor IIH. Nat Genet. 2004;36:707-13 pubmed
    ..The identification of a new, evolutionarily conserved, core TFIIH subunit is essential for our understanding of TFIIH function in transcription, DNA repair and human disease. ..
  2. Di Lello P, Nguyen B, Jones T, Potempa K, Kobor M, Legault P, et al. NMR structure of the amino-terminal domain from the Tfb1 subunit of TFIIH and characterization of its phosphoinositide and VP16 binding sites. Biochemistry. 2005;44:7678-86 pubmed
    ..These results provide new information about the recognition of phosphoinositides by PH domains, and point to a potential role for phosphoinositides in VP16 regulation. ..
  3. Compe E, Drané P, Laurent C, Diderich K, Braun C, Hoeijmakers J, et al. Dysregulation of the peroxisome proliferator-activated receptor target genes by XPD mutations. Mol Cell Biol. 2005;25:6065-76 pubmed
    ..This work emphasizes that underphosphorylation of PPARs affects their transactivation and consequently the expression of PPAR target genes, thus contributing in part to the XP-D phenotype. ..
  4. Rochette Egly C, Adam S, Rossignol M, Egly J, Chambon P. Stimulation of RAR alpha activation function AF-1 through binding to the general transcription factor TFIIH and phosphorylation by CDK7. Cell. 1997;90:97-107 pubmed
    ..Both free CAK (cdk7, cyclin H, MAT1) and the CAK-containing general transcription factor TFIIH phosphorylated Ser-77 in vitro...
  5. Boyle J, Ueda T, Oh K, Imoto K, Tamura D, Jagdeo J, et al. Persistence of repair proteins at unrepaired DNA damage distinguishes diseases with ERCC2 (XPD) mutations: cancer-prone xeroderma pigmentosum vs. non-cancer-prone trichothiodystrophy. Hum Mutat. 2008;29:1194-208 pubmed publisher
    ..In contrast, in TTD, low levels of unstable TFIIH proteins do not accumulate at sites of unrepaired photoproducts and may permit normal translesion DNA synthesis without increased skin cancer...
  6. Di Lello P, Miller Jenkins L, Mas C, Langlois C, Malitskaya E, Fradet Turcotte A, et al. p53 and TFIIEalpha share a common binding site on the Tfb1/p62 subunit of TFIIH. Proc Natl Acad Sci U S A. 2008;105:106-11 pubmed
    ..These results point to an important interplay between the general transcription factor TFIIEalpha and the tumor suppressor protein p53 in regulating transcriptional activation that may be modulated by the phosphorylation status of p53. ..
  7. Qadri I, Conaway J, Conaway R, Schaack J, Siddiqui A. Hepatitis B virus transactivator protein, HBx, associates with the components of TFIIH and stimulates the DNA helicase activity of TFIIH. Proc Natl Acad Sci U S A. 1996;93:10578-83 pubmed
    ..Furthermore, the DNA helicase activity of purified TFIIH from rat liver and, individually, the ERCC2 component of TFIIH is stimulated in the presence of HBx. These observations suggest a role for HBx in transcription and DNA repair. ..
  8. Pal M, Ponticelli A, Luse D. The role of the transcription bubble and TFIIB in promoter clearance by RNA polymerase II. Mol Cell. 2005;19:101-10 pubmed
    ..Our results indicate that bubble collapse defines the RNA polymerase II promoter clearance transition. ..
  9. Jona G, Livi L, Gileadi O. Mutations in the RING domain of TFB3, a subunit of yeast transcription factor IIH, reveal a role in cell cycle progression. J Biol Chem. 2002;277:39409-16 pubmed
    The RNA polymerase II general transcription factor TFIIH is composed of 9 known subunits and possesses DNA helicase and protein kinase activities...
  10. Korsisaari N, Rossi D, Paetau A, Charnay P, Henkemeyer M, Makela T. Conditional ablation of the Mat1 subunit of TFIIH in Schwann cells provides evidence that Mat1 is not required for general transcription. J Cell Sci. 2002;115:4275-84 pubmed part of the Cdk activating kinase (CAK), and in regulation of transcription as a subunit of transcription factor TFIIH. To address the role of Mat1 in vivo, we have used a Cre/loxP system to conditionally ablate Mat1 in ..
  11. Drapkin R, Reardon J, Ansari A, Huang J, Zawel L, Ahn K, et al. Dual role of TFIIH in DNA excision repair and in transcription by RNA polymerase II. Nature. 1994;368:769-72 pubmed
    The RNA polymerase II general transcription factor TFIIH is composed of several polypeptides. The observation that the largest subunit of TFIIH is the excision-repair protein XPB/ERCC3 (ref...
  12. Fregoso M, Laine J, Aguilar Fuentes J, Mocquet V, Reynaud E, Coin F, et al. DNA repair and transcriptional deficiencies caused by mutations in the Drosophila p52 subunit of TFIIH generate developmental defects and chromosome fragility. Mol Cell Biol. 2007;27:3640-50 pubmed
    ..This study significantly extends the role of p52 in regulating XPB ATPase activity and, consequently, both its transcriptional and nucleotide excision repair functions...
  13. Hoogstraten D, Nigg A, Heath H, Mullenders L, van Driel R, Hoeijmakers J, et al. Rapid switching of TFIIH between RNA polymerase I and II transcription and DNA repair in vivo. Mol Cell. 2002;10:1163-74 pubmed
    ..Our findings support a model of diffusion and random collision of individual components that permits a quick and versatile response to changing conditions. ..
  14. Andressoo J, Jans J, de Wit J, Coin F, Hoogstraten D, van de Ven M, et al. Rescue of progeria in trichothiodystrophy by homozygous lethal Xpd alleles. PLoS Biol. 2006;4:e322 pubmed
    ..Our data suggest a re-evaluation of the contribution of "null" alleles to XPD disorders and highlight the potential of combinations of recessive alleles to affect both normal and pathological phenotypic plasticity in mammals. ..
  15. Gervais V, Lamour V, Jawhari A, Frindel F, Wasielewski E, Dubaele S, et al. TFIIH contains a PH domain involved in DNA nucleotide excision repair. Nat Struct Mol Biol. 2004;11:616-22 pubmed
    The human general transcription factor TFIIH is involved in both transcription and DNA repair...
  16. Zotter A, Luijsterburg M, Warmerdam D, Ibrahim S, Nigg A, van Cappellen W, et al. Recruitment of the nucleotide excision repair endonuclease XPG to sites of UV-induced dna damage depends on functional TFIIH. Mol Cell Biol. 2006;26:8868-79 pubmed
    ..Together, our data present a comprehensive view of the in vivo behavior of a protein that is involved in a complex chromatin-associated process. ..
  17. Sarker A, Tsutakawa S, Kostek S, Ng C, Shin D, Peris M, et al. Recognition of RNA polymerase II and transcription bubbles by XPG, CSB, and TFIIH: insights for transcription-coupled repair and Cockayne Syndrome. Mol Cell. 2005;20:187-98 pubmed
    ..Together, these results implicate coordinated recognition of stalled transcription by XPG and CSB in TCR initiation and suggest that TFIIH-dependent remodeling of stalled RNAPII without release may be sufficient to allow repair...
  18. Ohkuma Y. Multiple functions of general transcription factors TFIIE and TFIIH in transcription: possible points of regulation by trans-acting factors. J Biochem. 1997;122:481-9 pubmed
    ..In this review, an overall perspective of the functional roles of TFIIE and TFIIH during transcription initiation and the following promoter clearance will be presented as it has emerged from recent studies. ..
  19. Ito S, Kuraoka I, Chymkowitch P, Compe E, Takedachi A, Ishigami C, et al. XPG stabilizes TFIIH, allowing transactivation of nuclear receptors: implications for Cockayne syndrome in XP-G/CS patients. Mol Cell. 2007;26:231-43 pubmed
    ..These results provide an insight into the role of XPG in the stabilization of TFIIH and the regulation of gene expression and provide an explanation of some of the clinical features of XP-G/CS...
  20. Merino C, Reynaud E, Vázquez M, Zurita M. DNA repair and transcriptional effects of mutations in TFIIH in Drosophila development. Mol Biol Cell. 2002;13:3246-56 pubmed
    ..In addition the apoptosis induced by p53 Drosophila homolog (Dmp53) is suppressed in heterozygous hay flies. ..
  21. Maxon M, Goodrich J, Tjian R. Transcription factor IIE binds preferentially to RNA polymerase IIa and recruits TFIIH: a model for promoter clearance. Genes Dev. 1994;8:515-24 pubmed
    ..These multiple interactions between TFIIE, Pol II and TFIIH support a model in which TFIIE plays a role in promoter clearance as well as in the recruitment of proteins required for transcription-coupled DNA repair. ..
  22. Keriel A, Stary A, Sarasin A, Rochette Egly C, Egly J. XPD mutations prevent TFIIH-dependent transactivation by nuclear receptors and phosphorylation of RARalpha. Cell. 2002;109:125-35 pubmed
    ..Thus, we demonstrate that the cdk7 kinase of TFIIH phosphorylates the nuclear receptor, then allowing ligand-dependent control of the activation of the hormone-responsive genes. ..
  23. Xiao H, Pearson A, Coulombe B, Truant R, Zhang S, Regier J, et al. Binding of basal transcription factor TFIIH to the acidic activation domains of VP16 and p53. Mol Cell Biol. 1994;14:7013-24 pubmed
    ..herpes simplex virus VP16 and human p53, directly interact with the multisubunit human general transcription factor TFIIH and its Saccharomyces cerevisiae counterpart, factor b...
  24. Lee D, Duan H, Chang C. From androgen receptor to the general transcription factor TFIIH. Identification of cdk activating kinase (CAK) as an androgen receptor NH(2)-terminal associated coactivator. J Biol Chem. 2000;275:9308-13 pubmed
    ..using protein A-Sepharose coupled with anti-AR antibody indicates that the AR interacts with the general transcription factor TFIIH in a physiological condition...
  25. Adamczewski J, Rossignol M, Tassan J, Nigg E, Moncollin V, Egly J. MAT1, cdk7 and cyclin H form a kinase complex which is UV light-sensitive upon association with TFIIH. EMBO J. 1996;15:1877-84 pubmed
    ..Although not strictly required for the formation and activity of the complex, it stimulates its kinase activity. The kinase activity of TFIIH, which is constant during the cell cycle, is reduced after UV light irradiation. ..
  26. Hwang J, Moncollin V, Vermeulen W, Seroz T, van Vuuren H, Hoeijmakers J, et al. A 3' --> 5' XPB helicase defect in repair/transcription factor TFIIH of xeroderma pigmentosum group B affects both DNA repair and transcription. J Biol Chem. 1996;271:15898-904 pubmed
    XPB is a subunit of the basal transcription factor TFIIH, which is also involved in nucleotide excision repair (NER) and potentially in cell cycle regulation...
  27. de Boer J, van Steeg H, Berg R, Garssen J, de Wit J, van Oostrum C, et al. Mouse model for the DNA repair/basal transcription disorder trichothiodystrophy reveals cancer predisposition. Cancer Res. 1999;59:3489-94 pubmed
    ..These findings have important implications for the etiology of the human disorder and for the impact of NER on carcinogenesis. ..
  28. Tantin D. 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. J Biol Chem. 1998;273:27794-9 pubmed
    ..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. ..
  29. Lehmann A. Dual functions of DNA repair genes: molecular, cellular, and clinical implications. Bioessays. 1998;20:146-55 pubmed
    ..This is illustrated most clearly in the transcription factor TFIIH, which is involved in both basal transcription and nucleotide excision repair...
  30. Habraken Y, Sung P, Prakash S, Prakash L. Transcription factor TFIIH and DNA endonuclease Rad2 constitute yeast nucleotide excision repair factor 3: implications for nucleotide excision repair and Cockayne syndrome. Proc Natl Acad Sci U S A. 1996;93:10718-22 pubmed
    ..Our findings are important for understanding the manner of assembly of the NER machinery and they have implications for Cockayne syndrome. ..
  31. Weeda G, Eveno E, Donker I, Vermeulen W, Chevallier Lagente O, Taieb A, et al. A mutation in the XPB/ERCC3 DNA repair transcription gene, associated with trichothiodystrophy. Am J Hum Genet. 1997;60:320-9 pubmed
    ..the clinical heterogeneity associated with XP-B, stress the exclusive relationship between TTD and mutations in subunits of repair/transcription factor TFIIH, and strongly support the concept of "transcription syndromes."
  32. Feaver W, Henry N, Wang Z, Wu X, Svejstrup J, Bushnell D, et al. Genes for Tfb2, Tfb3, and Tfb4 subunits of yeast transcription/repair factor IIH. Homology to human cyclin-dependent kinase activating kinase and IIH subunits. J Biol Chem. 1997;272:19319-27 pubmed
    ..These and other findings reveal a one-to-one correspondence and high degree of sequence similarity between the entire set of yeast and human TFIIH polypeptides. ..
  33. Iben S, Tschochner H, Bier M, Hoogstraten D, Hozak P, Egly J, et al. TFIIH plays an essential role in RNA polymerase I transcription. Cell. 2002;109:297-306 pubmed
    ..The results provide a molecular link between RNA polymerase I transcription and transcription-coupled repair of active ribosomal RNA genes. ..
  34. Gibbons B, Brignole E, Azubel M, Murakami K, Voss N, Bushnell D, et al. Subunit architecture of general transcription factor TFIIH. Proc Natl Acad Sci U S A. 2012;109:1949-54 pubmed publisher
    ..In this picture, the key catalytic components of TFIIH, the Ssl2 ATPase/helicase and the Kin28 protein kinase are in proximity to their targets, downstream promoter DNA and the RNA polymerase C-terminal domain. ..
  35. Shiekhattar R, Mermelstein F, Fisher R, Drapkin R, Dynlacht B, Wessling H, et al. Cdk-activating kinase complex is a component of human transcription factor TFIIH. Nature. 1995;374:283-7 pubmed
    ..Both Cak complexes, as well as recombinant Cak, phosphorylate a CTD peptide. Finally, TFIIH was shown to phosphorylate both Cdc2 and Cdk2, suggesting that there could be a link between transcription and the cell cycle machinery. ..
  36. Viladevall L, St Amour C, Rosebrock A, Schneider S, Zhang C, Allen J, et al. TFIIH and P-TEFb coordinate transcription with capping enzyme recruitment at specific genes in fission yeast. Mol Cell. 2009;33:738-51 pubmed publisher
    ..In vitro, phosphorylation of the CTD by Mcs6 stimulates subsequent phosphorylation by Cdk9. We propose that TFIIH primes the CTD and promotes recruitment of P-TEFb/Pcm1, serving to couple elongation and capping of select pre-mRNAs. ..
  37. Svejstrup J, Feaver W, Lapointe J, Kornberg R. RNA polymerase transcription factor IIH holoenzyme from yeast. J Biol Chem. 1994;269:28044-8 pubmed
    ..By contrast, core TFIIH is inert in both C-terminal repeat domain kinase and reconstituted transcription assays. ..
  38. Lee J, Nguyen T, Schimanski B, GUNZL A. Spliced leader RNA gene transcription in Trypanosoma brucei requires transcription factor TFIIH. Eukaryot Cell. 2007;6:641-9 pubmed
    ..Since we also identified orthologues of the TFIIH subunits XPB, p52/TFB2, and p44/SSL1 copurifying with TbXPD, we concluded that the parasite harbors a TFIIH which is indispensable for SL RNA gene transcription. ..
  39. Takagi Y, Masuda C, Chang W, Komori H, Wang D, Hunter T, et al. Ubiquitin ligase activity of TFIIH and the transcriptional response to DNA damage. Mol Cell. 2005;18:237-43 pubmed
    ..Rather, it correlates with reduced transcriptional induction of genes involved in DNA repair, suggesting that the E3 Ub ligase activity of TFIIH mediates the transcriptional response to DNA damage. ..
  40. Giglia Mari G, Coin F, Ranish J, Hoogstraten D, Theil A, Wijgers N, et al. A new, tenth subunit of TFIIH is responsible for the DNA repair syndrome trichothiodystrophy group A. Nat Genet. 2004;36:714-9 pubmed
    ..trichothiodystrophy (TTD) results from mutations in the XPD and XPB subunits of the DNA repair and transcription factor TFIIH. In a third form of DNA repair-deficient TTD, called group A, none of the nine subunits encoding TFIIH ..
  41. Takagi Y, Komori H, Chang W, Hudmon A, Erdjument Bromage H, Tempst P, et al. Revised subunit structure of yeast transcription factor IIH (TFIIH) and reconciliation with human TFIIH. J Biol Chem. 2003;278:43897-900 pubmed
    ..This reassignment of subunits resolves a longstanding discrepancy between yeast and human TFIIH complexes. ..
  42. Fukuda A, Tokonabe S, Hamada M, Matsumoto M, Tsukui T, Nogi Y, et al. Alleviation of PC4-mediated transcriptional repression by the ERCC3 helicase activity of general transcription factor TFIIH. J Biol Chem. 2003;278:14827-31 pubmed
    ..studies showed that the repressive activity of PC4 on promoter-driven transcription is alleviated by transcription factor TFIIH, possibly through one of its enzymatic activities...
  43. Botta E, Nardo T, Lehmann A, Egly J, Pedrini A, Stefanini M. Reduced level of the repair/transcription factor TFIIH in trichothiodystrophy. Hum Mol Genet. 2002;11:2919-28 pubmed
  44. Chang W, Kornberg R. Electron crystal structure of the transcription factor and DNA repair complex, core TFIIH. Cell. 2000;102:609-13 pubmed
    ..The structure is based on a ring of three subunits, Tfb1, Tfb2, and Tfb3, to which are appended several functional moieties: Rad3, bridged to Tfb1 by SsI1; SsI2, known to interact with Tfb2; and Kin28, known to interact with Tfb3. ..
  45. Lehmann A. The xeroderma pigmentosum group D (XPD) gene: one gene, two functions, three diseases. Genes Dev. 2001;15:15-23 pubmed
  46. Moné M, Volker M, Nikaido O, Mullenders L, van Zeeland A, Verschure P, et al. Local UV-induced DNA damage in cell nuclei results in local transcription inhibition. EMBO Rep. 2001;2:1013-7 pubmed
    ..This result was obtained for cells that are able to carry out NER and for cells deficient in NER. We conclude that cross talk between NER and transcription occurs only over short distances in nuclei of living cells. ..
  47. Serizawa H. Cyclin-dependent kinase inhibitor p16INK4A inhibits phosphorylation of RNA polymerase II by general transcription factor TFIIH. J Biol Chem. 1998;273:5427-30 pubmed
    ..General transcription factor TFIIH, which contains CDK7, phosphorylates the CTD in vitro...
  48. Weeda G, Rossignol M, Fraser R, Winkler G, Vermeulen W, van T Veer L, et al. The XPB subunit of repair/transcription factor TFIIH directly interacts with SUG1, a subunit of the 26S proteasome and putative transcription factor. Nucleic Acids Res. 1997;25:2274-83 pubmed
    ..Since SUG1 is an integral component of the 26S proteasome and may be part of the mediator, our findings disclose a SUG1-dependent link between TFIIH and the cellular machinery involved in protein modelling/degradation. ..
  49. Miller G, Hahn S. A DNA-tethered cleavage probe reveals the path for promoter DNA in the yeast preinitiation complex. Nat Struct Mol Biol. 2006;13:603-10 pubmed
    ..Together, our results show how the general factors and Pol II converge on promoter DNA within the PIC. ..
  50. Watanabe T, Hayashi K, Tanaka A, Furumoto T, Hanaoka F, Ohkuma Y. The carboxy terminus of the small subunit of TFIIE regulates the transition from transcription initiation to elongation by RNA polymerase II. Mol Cell Biol. 2003;23:2914-26 pubmed
    ..This is an important clue for elucidating the molecular mechanisms involved in the transition stage. ..
  51. Bardwell L, Bardwell A, Feaver W, Svejstrup J, Kornberg R, Friedberg E. Yeast RAD3 protein binds directly to both SSL2 and SSL1 proteins: implications for the structure and function of transcription/repair factor b. Proc Natl Acad Sci U S A. 1994;91:3926-30 pubmed
    ..We present genetic evidence suggesting that the DNA-repair function of SSL2 protein is not dependent on its essential function. ..
  52. Matsuno M, Kose H, Okabe M, Hiromi Y. TFIIH controls developmentally-regulated cell cycle progression as a holocomplex. Genes Cells. 2007;12:1289-300 pubmed
    ..We propose that during development the function of TFIIH as a cell cycle regulator is carried out by holo-TFIIH. ..
  53. Bergmann E, Egly J. Trichothiodystrophy, a transcription syndrome. Trends Genet. 2001;17:279-86 pubmed
    ..In a third group of photosensitive patients, TTD-A, no mutation has been identified, although TFIIH amount is reduced. ..