XPB
XPB (
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.[5]
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).[6] Mutant XPB cells from individuals with the XPCS phenotype are sensitive to UV irradiation and acute oxidative stress.[7]
Disorders
Mutations in XPB and other related complementation groups, XPA-XPG, leads to a number of genetic disorders such as
Cockayne's syndrome, and trichothiodystrophy
.
Interactions
XPB has been shown to
interact
with:
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.[18]
See also
- XP
References
- ^ a b c GRCh38: Ensembl release 89: ENSG00000163161 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000024382 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- PMID 16600867.
- S2CID 22852219.
- PMID 19114557.
- PMID 9874796.
- ^ PMID 15220921.
- ^ PMID 9130708.
- PMID 8521393.
- ^ PMID 9118947.
- S2CID 4363484.
- PMID 8652557.
- S2CID 38325851.
- PMID 9173976.
- PMID 10734143.
- PMID 33083765.
Further reading
- Jeang KT (1998). "Tat, Tat-associated kinase, and transcription". J. Biomed. Sci. 5 (1): 24–7. PMID 9570510.
- Yankulov K, Bentley D (1998). "Transcriptional control: Tat cofactors and transcriptional elongation". Curr. Biol. 8 (13): R447–9. S2CID 15480646.
- Cleaver JE, Thompson LH, Richardson AS, States JC (1999). "A summary of mutations in the UV-sensitive disorders: xeroderma pigmentosum, Cockayne syndrome, and trichothiodystrophy". Hum. Mutat. 14 (1): 9–22. S2CID 24148589.
- Ma L, Weeda G, Jochemsen AG, Bootsma D, Hoeijmakers JH, van der Eb AJ (1992). "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. PMID 1741247.
- Weeda G, Wiegant J, van der Ploeg M, Geurts van Kessel AH, van der Eb AJ, Hoeijmakers JH (1991). "Localization of the xeroderma pigmentosum group B-correcting gene ERCC3 to human chromosome 2q21". Genomics. 10 (4): 1035–1040. PMID 1916809.
- Weeda G, Ma LB, van Ham RC, van der Eb AJ, Hoeijmakers JH (1991). "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. PMID 1956789.
- Weeda G, van Ham RC, Masurel R, Westerveld A, Odijk H, de Wit J, Bootsma D, van der Eb AJ, Hoeijmakers JH (1990). "Molecular cloning and biological characterization of the human excision repair gene ERCC-3". Mol. Cell. Biol. 10 (6): 2570–2581. PMID 2111438.
- Weeda G, van Ham RC, Vermeulen W, Bootsma D, van der Eb AJ, Hoeijmakers JH (1990). "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. S2CID 31743602.
- Wang XW, Yeh H, Schaeffer L, Roy R, Moncollin V, Egly JM, Wang Z, Freidberg EC, Evans MK, Taffe BG (1995). "p53 modulation of TFIIH-associated nucleotide excision repair activity". Nat. Genet. 10 (2): 188–95. S2CID 38325851.
- Maxon ME, Goodrich JA, Tjian R (1994). "Transcription factor IIE binds preferentially to RNA polymerase IIa and recruits TFIIH: a model for promoter clearance". Genes Dev. 8 (5): 515–24. PMID 7926747.
- Maruyama K, Sugano S (1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene. 138 (1–2): 171–4. PMID 8125298.
- Drapkin R, Reardon JT, Ansari A, Huang JC, Zawel L, Ahn K, Sancar A, Reinberg D (1994). "Dual role of TFIIH in DNA excision repair and in transcription by RNA polymerase II". Nature. 368 (6473): 769–72. S2CID 4363484.
- van Vuuren AJ, Vermeulen W, Ma L, Weeda G, Appeldoorn E, Jaspers NG, van der Eb AJ, Bootsma D, Hoeijmakers JH, Humbert S (1994). "Correction of xeroderma pigmentosum repair defect by basal transcription factor BTF2 (TFIIH)". EMBO J. 13 (7): 1645–1653. PMID 8157004.
- Schaeffer L, Moncollin V, Roy R, Staub A, Mezzina M, Sarasin A, Weeda G, Hoeijmakers JH, Egly JM (1994). "The ERCC2/DNA repair protein is associated with the class II BTF2/TFIIH transcription factor". EMBO J. 13 (10): 2388–2392. PMID 8194528.
- Guzder SN, Sung P, Bailly V, Prakash L, Prakash S (1994). "RAD25 is a DNA helicase required for DNA repair and RNA polymerase II transcription". Nature. 369 (6481): 578–81. S2CID 4332757.
- Vermeulen W, Scott RJ, Rodgers S, Müller HJ, Cole J, Arlett CF, Kleijer WJ, Bootsma D, Hoeijmakers JH, Weeda G (1994). "Clinical heterogeneity within xeroderma pigmentosum associated with mutations in the DNA repair and transcription gene ERCC3". Am. J. Hum. Genet. 54 (2): 191–200. PMID 8304337.
- Scott RJ, Itin P, Kleijer WJ, Kolb K, Arlett C, Muller H (1993). "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. PMID 8408834.
- Blau J, Xiao H, McCracken S, O'Hare P, Greenblatt J, Bentley D (1996). "Three functional classes of transcriptional activation domain". Mol. Cell. Biol. 16 (5): 2044–2055. PMID 8628270.
- Iyer N, Reagan MS, Wu KJ, Canagarajah B, Friedberg EC (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): 2157–2167. PMID 8652557.
- Hwang JR, Moncollin V, Vermeulen W, Seroz T, van Vuuren H, Hoeijmakers JH, Egly JM (1996). "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. PMID 8663148.
External links
- GeneReviews/NIH/NCBI/UW entry on Xeroderma Pigmentosum
- XPBC-ERCC-3+protein at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
| Other forms of repair |
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|---|---|---|
| Other/ungrouped proteins | ||
| Regulation | ||
| Other/ungrouped |
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