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XPB

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ERCC3
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesERCC3, excision repair cross-complementation group 3, BTF2, GTF2H, RAD25, TFIIH, XPB, TTD2, ERCC excision repair 3, TFIIH core complex helicase subunit, Ssl2
External IDsOMIM: 133510; MGI: 95414; HomoloGene: 96; GeneCards: ERCC3; OMA:ERCC3 - orthologs
Orthologs
SpeciesHumanMouse
Entrez

2071

13872

Ensembl

ENSG00000163161

ENSMUSG00000024382

UniProt

P19447

P49135

RefSeq (mRNA)

NM_000122
NM_001303416
NM_001303418

NM_133658

RefSeq (protein)

NP_000113
NP_001290345
NP_001290347

NP_598419

Location (UCSC)Chr 2: 127.26 – 127.29 MbChr 18: 32.37 – 32.4 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

XPB (xeroderma pigmentosum type B) is an ATP-dependent DNA helicase in humans that is a part of the TFIIH transcription factor complex.

Structure

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The 3D-structure of the archaeal homolog of XPB has been solved by X-ray crystallography by Dr. John Tainer and his group at The Scripps Research Institute.[5]

Function

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XPB plays a significant role in normal basal transcription, transcription coupled repair (TCR), and nucleotide excision repair (NER). Purified XPB has been shown to unwind DNA with 3’-5’ polarity.

The function of the XPB(ERCC3) protein in NER is to assist in unwinding the DNA double helix after damage is initially recognized. NER is a multi-step pathway that removes a wide range of different DNA damages that distort normal base pairing. Such damages include bulky chemical adducts, UV-induced pyrimidine dimers, and several forms of oxidative damage. Mutations in the XPB(ERCC3) gene can lead, in humans, to xeroderma pigmentosum (XP) or XP combined with Cockayne syndrome (XPCS).[6] Mutant XPB cells from individuals with the XPCS phenotype are sensitive to UV irradiation and acute oxidative stress.[7]

XPB helicase is also a component of the p53-mediated programmed cell death (apoptosis) pathway.[8]

Disorders

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Mutations in XPB and other related complementation groups, XPA-XPG, leads to a number of genetic disorders such as Xeroderma pigmentosum, Cockayne's syndrome, and trichothiodystrophy.

Interactions

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XPB has been shown to interact with:

Small molecule inhibitors

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Potent, bioactive natural products like triptolide that inhibit mammalian transcription via inhibition of the XPB subunit of the general transcription factor TFIIH has been recently reported as a glucose conjugate for targeting hypoxic cancer cells with increased glucose transporter expression.[19]

See also

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References

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  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000163161 – Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000024382 – Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ Fan L, Arvai AS, Cooper PK, Iwai S, Hanaoka F, Tainer JA (April 2006). "Conserved XPB Core Structure and Motifs for DNA Unwinding: Implications for Pathway Selection of Transcription or Excision Repair". Molecular Cell. 22 (1): 27–37. doi:10.1016/j.molcel.2006.02.017. PMID 16600867.
  6. ^ 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 (2006). "Phenotypic heterogeneity in the XPB DNA helicase gene (ERCC3): xeroderma pigmentosum without and with Cockayne syndrome". Hum. Mutat. 27 (11): 1092–103. doi:10.1002/humu.20392. PMID 16947863. S2CID 22852219.
  7. ^ Andressoo JO, Weeda G, de Wit J, Mitchell JR, Beems RB, van Steeg H, van der Horst GT, Hoeijmakers JH (2009). "An Xpb mouse model for combined xeroderma pigmentosum and cockayne syndrome reveals progeroid features upon further attenuation of DNA repair". Mol. Cell. Biol. 29 (5): 1276–90. doi:10.1128/MCB.01229-08. PMC 2643825. PMID 19114557.
  8. ^ Wang XW, Vermeulen W, Coursen JD, Gibson M, Lupold SE, Forrester K, Xu G, Elmore L, Yeh H, Hoeijmakers JH, Harris CC (May 1996). "The XPB and XPD DNA helicases are components of the p53-mediated apoptosis pathway". Genes Dev. 10 (10): 1219–32. doi:10.1101/gad.10.10.1219. hdl:1765/3094. PMID 8675009.
  9. ^ Takeda N, Shibuya M, Maru Y (January 1999). "The BCR-ABL oncoprotein potentially interacts with the xeroderma pigmentosum group B protein". Proc. Natl. Acad. Sci. U.S.A. 96 (1): 203–7. Bibcode:1999PNAS...96..203T. doi:10.1073/pnas.96.1.203. PMC 15117. PMID 9874796.
  10. ^ a b c d e f Giglia-Mari G, Coin F, Ranish JA, Hoogstraten D, Theil A, Wijgers N, Jaspers NG, Raams A, Argentini M, van der Spek PJ, Botta E, Stefanini M, Egly JM, Aebersold R, Hoeijmakers JH, Vermeulen W (July 2004). "A new, tenth subunit of TFIIH is responsible for the DNA repair syndrome trichothiodystrophy group A". Nat. Genet. 36 (7): 714–9. doi:10.1038/ng1387. PMID 15220921.
  11. ^ a b Rossignol M, Kolb-Cheynel I, Egly JM (April 1997). "Substrate specificity of the cdk-activating kinase (CAK) is altered upon association with TFIIH". EMBO J. 16 (7): 1628–37. doi:10.1093/emboj/16.7.1628. PMC 1169767. PMID 9130708.
  12. ^ Yee A, Nichols MA, Wu L, Hall FL, Kobayashi R, Xiong Y (December 1995). "Molecular cloning of CDK7-associated human MAT1, a cyclin-dependent kinase-activating kinase (CAK) assembly factor". Cancer Res. 55 (24): 6058–62. PMID 8521393.
  13. ^ a b c d Marinoni JC, Roy R, Vermeulen W, Miniou P, Lutz Y, Weeda G, Seroz T, Gomez DM, Hoeijmakers JH, Egly JM (March 1997). "Cloning and characterization of p52, the fifth subunit of the core of the transcription/DNA repair factor TFIIH". EMBO J. 16 (5): 1093–102. doi:10.1093/emboj/16.5.1093. PMC 1169708. PMID 9118947.
  14. ^ 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. Bibcode:1994Natur.368..769D. doi:10.1038/368769a0. PMID 8152490. S2CID 4363484.
  15. ^ Iyer N, Reagan MS, Wu KJ, Canagarajah B, Friedberg EC (February 1996). "Interactions involving the human RNA polymerase II transcription/nucleotide excision repair complex TFIIH, the nucleotide excision repair protein XPG, and Cockayne syndrome group B (CSB) protein". Biochemistry. 35 (7): 2157–67. doi:10.1021/bi9524124. PMID 8652557.
  16. ^ Wang XW, Yeh H, Schaeffer L, Roy R, Moncollin V, Egly JM, Wang Z, Freidberg EC, Evans MK, Taffe BG (June 1995). "p53 modulation of TFIIH-associated nucleotide excision repair activity". Nat. Genet. 10 (2): 188–95. doi:10.1038/ng0695-188. hdl:1765/54884. PMID 7663514. S2CID 38325851.
  17. ^ Weeda G, Rossignol M, Fraser RA, Winkler GS, Vermeulen W, van 't Veer LJ, Ma L, Hoeijmakers JH, Egly JM (June 1997). "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. 25 (12): 2274–83. doi:10.1093/nar/25.12.2274. PMC 146752. PMID 9173976.
  18. ^ Yokoi M, Masutani C, Maekawa T, Sugasawa K, Ohkuma Y, Hanaoka F (March 2000). "The xeroderma pigmentosum group C protein complex XPC-HR23B plays an important role in the recruitment of transcription factor IIH to damaged DNA". J. Biol. Chem. 275 (13): 9870–5. doi:10.1074/jbc.275.13.9870. PMID 10734143.
  19. ^ Datan E, Minn I, Peng X, He QL, Ahn H, Yu B, Pomper MG, Liu JO (2020). "A Glucose-Triptolide Conjugate Selectively Targets Cancer Cells under Hypoxia". iScience. 23 (9): 101536. Bibcode:2020iSci...23j1536D. doi:10.1016/j.isci.2020.101536. PMC 7509213. PMID 33083765.

Further reading

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