Biology:XPB
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Short description: Mammalian protein found in Homo sapiens
 Generic protein structure example |
XPB (xeroderma pigmentosum type B) is an ATP-dependent DNA helicase in humans that is a part of the TFIIH transcription factor complex.
Structure
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.[1]
Function
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).[2] Mutant XPB cells from individuals with the XPCS phenotype are sensitive to UV irradiation and acute oxidative stress.[3]
Disorders
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
XPB has been shown to interact with:
- BCR gene,[4]
- CDK7,[5][6][7]
- ERCC2,[5][8][9][10]
- GTF2H1,[5][6][8]
- GTF2H2,[5][8]
- GTF2H4,[5][8]
- GTF2H5,[5]
- P53,[11]
- PSMC5,[12] and
- XPC.[13]
Small molecule inhibitors
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.[14]
See also
- XP
References
- ↑ "Conserved XPB Core Structure and Motifs for DNA Unwinding: Implications for Pathway Selection of Transcription or Excision Repair". Molecular Cell 22 (1): 27–37. April 2006. doi:10.1016/j.molcel.2006.02.017. PMID 16600867.
- ↑ "Phenotypic heterogeneity in the XPB DNA helicase gene (ERCC3): xeroderma pigmentosum without and with Cockayne syndrome". Hum. Mutat. 27 (11): 1092–103. 2006. doi:10.1002/humu.20392. PMID 16947863.
- ↑ "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. 2009. doi:10.1128/MCB.01229-08. PMID 19114557.
- ↑ "The BCR-ABL oncoprotein potentially interacts with the xeroderma pigmentosum group B protein". Proc. Natl. Acad. Sci. U.S.A. 96 (1): 203–7. January 1999. doi:10.1073/pnas.96.1.203. PMID 9874796. Bibcode: 1999PNAS...96..203T.
- ↑ 5.0 5.1 5.2 5.3 5.4 5.5 "A new, tenth subunit of TFIIH is responsible for the DNA repair syndrome trichothiodystrophy group A". Nat. Genet. 36 (7): 714–9. July 2004. doi:10.1038/ng1387. PMID 15220921.
- ↑ 6.0 6.1 "Substrate specificity of the cdk-activating kinase (CAK) is altered upon association with TFIIH". EMBO J. 16 (7): 1628–37. April 1997. doi:10.1093/emboj/16.7.1628. PMID 9130708.
- ↑ "Molecular cloning of CDK7-associated human MAT1, a cyclin-dependent kinase-activating kinase (CAK) assembly factor". Cancer Res. 55 (24): 6058–62. December 1995. PMID 8521393.
- ↑ 8.0 8.1 8.2 8.3 "Cloning and characterization of p52, the fifth subunit of the core of the transcription/DNA repair factor TFIIH". EMBO J. 16 (5): 1093–102. March 1997. doi:10.1093/emboj/16.5.1093. PMID 9118947.
- ↑ "Dual role of TFIIH in DNA excision repair and in transcription by RNA polymerase II". Nature 368 (6473): 769–72. April 1994. doi:10.1038/368769a0. PMID 8152490. Bibcode: 1994Natur.368..769D.
- ↑ "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. February 1996. doi:10.1021/bi9524124. PMID 8652557.
- ↑ "p53 modulation of TFIIH-associated nucleotide excision repair activity". Nat. Genet. 10 (2): 188–95. June 1995. doi:10.1038/ng0695-188. PMID 7663514. http://repub.eur.nl/pub/54884.
- ↑ "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. June 1997. doi:10.1093/nar/25.12.2274. PMID 9173976.
- ↑ "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. March 2000. doi:10.1074/jbc.275.13.9870. PMID 10734143.
- ↑ "A Glucose-Triptolide Conjugate Selectively Targets Cancer Cells under Hypoxia". iScience 23 (9): 101536. 2020. doi:10.1016/j.isci.2020.101536. PMID 33083765. Bibcode: 2020iSci...23j1536D.
Further reading
- Jeang KT (1998). "Tat, Tat-associated kinase, and transcription.". J. Biomed. Sci. 5 (1): 24–7. doi:10.1007/BF02253352. PMID 9570510.
- "Transcriptional control: Tat cofactors and transcriptional elongation.". Curr. Biol. 8 (13): R447–9. 1998. doi:10.1016/S0960-9822(98)70289-1. PMID 9651670.
- "A summary of mutations in the UV-sensitive disorders: xeroderma pigmentosum, Cockayne syndrome, and trichothiodystrophy.". Hum. Mutat. 14 (1): 9–22. 1999. doi:10.1002/(SICI)1098-1004(1999)14:1<9::AID-HUMU2>3.0.CO;2-6. PMID 10447254.
- "Molecular and functional analysis of the XPBC/ERCC-3 promoter: transcription activity is dependent on the integrity of an Sp1-binding site.". Nucleic Acids Res. 20 (2): 217–24. 1992. doi:10.1093/nar/20.2.217. PMID 1741247.
- "Localization of the xeroderma pigmentosum group B-correcting gene ERCC3 to human chromosome 2q21.". Genomics 10 (4): 1035–1040. 1991. doi:10.1016/0888-7543(91)90195-K. PMID 1916809. http://repub.eur.nl/pub/3025.
- "Structure and expression of the human XPBC/ERCC-3 gene involved in DNA repair disorders xeroderma pigmentosum and Cockayne's syndrome.". Nucleic Acids Res. 19 (22): 6301–6308. 1991. doi:10.1093/nar/19.22.6301. PMID 1956789.
- "Molecular cloning and biological characterization of the human excision repair gene ERCC-3.". Mol. Cell. Biol. 10 (6): 2570–2581. 1990. doi:10.1128/MCB.10.6.2570. PMID 2111438.
- "A presumed DNA helicase encoded by ERCC-3 is involved in the human repair disorders xeroderma pigmentosum and Cockayne's syndrome.". Cell 62 (4): 777–91. 1990. doi:10.1016/0092-8674(90)90122-U. PMID 2167179. http://repub.eur.nl/pub/3020.
- "p53 modulation of TFIIH-associated nucleotide excision repair activity.". Nat. Genet. 10 (2): 188–95. 1995. doi:10.1038/ng0695-188. PMID 7663514. http://repub.eur.nl/pub/54884.
- "Transcription factor IIE binds preferentially to RNA polymerase IIa and recruits TFIIH: a model for promoter clearance.". Genes Dev. 8 (5): 515–24. 1994. doi:10.1101/gad.8.5.515. PMID 7926747.
- "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides.". Gene 138 (1–2): 171–4. 1994. doi:10.1016/0378-1119(94)90802-8. PMID 8125298.
- "Dual role of TFIIH in DNA excision repair and in transcription by RNA polymerase II". Nature 368 (6473): 769–72. 1994. doi:10.1038/368769a0. PMID 8152490. Bibcode: 1994Natur.368..769D.
- "Correction of xeroderma pigmentosum repair defect by basal transcription factor BTF2 (TFIIH)". EMBO J. 13 (7): 1645–1653. 1994. doi:10.1002/j.1460-2075.1994.tb06428.x. PMID 8157004.
- "The ERCC2/DNA repair protein is associated with the class II BTF2/TFIIH transcription factor". EMBO J. 13 (10): 2388–2392. 1994. doi:10.1002/j.1460-2075.1994.tb06522.x. PMID 8194528.
- "RAD25 is a DNA helicase required for DNA repair and RNA polymerase II transcription". Nature 369 (6481): 578–81. 1994. doi:10.1038/369578a0. PMID 8202161. Bibcode: 1994Natur.369..578G.
- "Clinical heterogeneity within xeroderma pigmentosum associated with mutations in the DNA repair and transcription gene ERCC3". Am. J. Hum. Genet. 54 (2): 191–200. 1994. PMID 8304337.
- "Xeroderma pigmentosum-Cockayne syndrome complex in two patients: absence of skin tumors despite severe deficiency of DNA excision repair". J. Am. Acad. Dermatol. 29 (5 Pt 2): 883–9. 1993. doi:10.1016/0190-9622(93)70263-S. PMID 8408834.
- "Three functional classes of transcriptional activation domain". Mol. Cell. Biol. 16 (5): 2044–2055. 1996. doi:10.1128/MCB.16.5.2044. PMID 8628270.
- "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): 2157–2167. 1996. doi:10.1021/bi9524124. PMID 8652557.
- "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. 271 (27): 15898–904. 1996. doi:10.1074/jbc.271.27.15898. PMID 8663148.
External links
- GeneReviews/NIH/NCBI/UW entry on Xeroderma Pigmentosum
- XPBC-ERCC-3+protein at the US National Library of Medicine Medical Subject Headings (MeSH)
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