Biology:XPB

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Short description: Mammalian protein found in Homo sapiens


A representation of the 3D structure of the protein myoglobin showing turquoise α-helices.
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:


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

  1. "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. 
  2. "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. 
  3. "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. 
  4. "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. Bibcode1999PNAS...96..203T. 
  5. 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. 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. 
  7. "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. 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. 
  9. "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. Bibcode1994Natur.368..769D. 
  10. "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. 
  11. "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. 
  12. "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. 
  13. "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. 
  14. "A Glucose-Triptolide Conjugate Selectively Targets Cancer Cells under Hypoxia". iScience 23 (9): 101536. 2020. doi:10.1016/j.isci.2020.101536. PMID 33083765. Bibcode2020iSci...23j1536D. 

Further reading

External links