TFIIH helicase XPB

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TFIIH helicase XPB

Existing structural data : 4ERN

Properties of human protein
Mass / length primary structure 782 amino acids
Identifier
Gene names ERCC3 BTF2; GTF2H; RAD25; TFIIH; TTD2; XPB
External IDs
Enzyme classification
EC, category 3.6.4.12 Helicase
Response type Isomerization
Substrate ATP + ds-DNA
Products ADP + phosphate + ds-DNA with 'bubble'
Occurrence
Parent taxon Eukaryotes , archaea
Orthologue
human House mouse
Entrez 2071 13872
Ensemble ENSG00000163161 ENSMUSG00000024382
UniProt P19447 P49135
Refseq (mRNA) NM_000122 NM_133658
Refseq (protein) NP_000113 NP_598419
Gene locus Chr 2: 127.26 - 127.29 Mb Chr 18: 32.24 - 32.27 Mb
PubMed search 2071 13872

The TFIIH helicase XPB is the enzyme in the nucleus of eukaryotes that, as part of the transcription factor IIH (TFIIH), catalyzes the opening of the DNA double strand after the pre-initiation complex has been assembled. This reaction step is part of the initiation of the transcription of all eukaryotic genes . In addition, XPB plays a very similar role in DNA repair . Mutations in the human ERCC3 gene, which codes for XPB , can lead to the rare hereditary disease Xeroderma pigmentosum type B, in which the risk of skin cancer is 2000 times higher, or to Tay syndrome , a rare ichthyosis .

The opening of the double strand consumes a molecule of ATP and spans the bases from −10 to +2 with respect to the beginning of the gene. It is supported by untwisting the DNA (so-called negative supercoiling ) with the help of TFIIE . The XPD helicase also takes part in DNA repair . The opened DNA is called a DNA bubble in both cases .

A protein orthologous to XPB has been found in archaea . Like the eukaryotic one, the XPB found has no helicase activity in vitro . The protein is believed to have a role in DNA repair.

XPB and XPD mimick part of the cell's defense against retroviral infection, a laboratory study. A Chinese study found that a combination of certain XPB and XPD variants increased the risk of lung cancer .

further reading

  • Beck BD, Hah DS, Lee SH: XPB and XPD between transcription and DNA repair . In: ... Adv Exp Med Biol. . 637, 2008, pp. 39-46. PMID 19181109 .
  • Coin F, Oksenych V, Egly JM: Distinct roles for the XPB / p52 and XPD / p44 subcomplexes of TFIIH in damaged DNA opening during nucleotide excision repair . In: Mol. Cell . 26, No. 2, April 2007, pp. 245-56. doi : 10.1016 / j.molcel.2007.03.009 . PMID 17466626 .
  • Hu GM, Liu LM, Zhang JX, et al. : The role of XPB in cell apoptosis and viability and its relationship with p53, p21 (waf1 / cip1) and c-myc in hepatoma cells . In: Dig Liver Dis . 38, No. 10, October 2006, pp. 755-61. doi : 10.1016 / j.dld.2006.06.009 . PMID 16914395 .

Individual evidence

  1. Homologues at OMA
  2. UniProt P19447
  3. Reinberg / reactome: RNA Polymerase II Promoter Opening: First Transition  ( page no longer available , search in web archivesInfo: The link was automatically marked as defective. Please check the link according to the instructions and then remove this notice.@1@ 2Template: Dead Link / www.reactome.org  
  4. Joshi-Tope / reactome: Formation of open bubble structure in DNA by helicases  ( page no longer available , search in web archivesInfo: The link was automatically marked as defective. Please check the link according to the instructions and then remove this notice.@1@ 2Template: Dead Link / www.reactome.org  
  5. Gopinathrao / reactome: Assembly of repair proteins at the site of Pol II blockage  ( page no longer available , search in web archivesInfo: The link was automatically marked as defective. Please check the link according to the instructions and then remove this notice.@1@ 2Template: Dead Link / www.reactome.org  
  6. Richards JD, Cubeddu L, Roberts J, Liu H, White MF: The archaeal XPB protein is a ssDNA-dependent ATPase with a novel partner . In: J. Mol. Biol. . 376, No. 3, February 2008, pp. 634-44. doi : 10.1016 / j.jmb.2007.12.019 . PMID 18177890 .
  7. Jump up ↑ Yoder K, Sarasin A, Kraemer K, McIlhatton M, Bushman F, Fishel R: The DNA repair genes XPB and XPD defend cells from retroviral infection . In: Proc. Natl. Acad. Sci. USA . 103, No. 12, March 2006, pp. 4622-7. doi : 10.1073 / pnas.0509828103 . PMID 16537383 . PMC 1450221 (free full text).
  8. Hu Z, Xu L, Shao M, et al. : Polymorphisms in the two helicases ERCC2 / XPD and ERCC3 / XPB of the transcription factor IIH complex and risk of lung cancer: a case-control analysis in a Chinese population . In: Cancer Epidemiol. Biomarkers Prev. . 15, No. 7, July 2006, pp. 1336-40. doi : 10.1158 / 1055-9965.EPI-06-0194 . PMID 16835333 .