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词条 XPC (gene)
释义

  1. Function

  2. Clinical significance

     Cancer 

  3. Interactions

  4. References

  5. Further reading

  6. External links

{{Infobox_gene}}Xeroderma pigmentosum, complementation group C, also known as XPC, is a protein which in humans is encoded by the XPC gene. XPC is involved in the recognition of bulky DNA adducts in nucleotide excision repair.[1] It is located on chromosome 3.[2]

Function

This gene encodes a component of the nucleotide excision repair (NER) pathway. There are multiple components involved in the NER pathway, including Xeroderma pigmentosum (XP) A-G and V, Cockayne syndrome (CS) A and B, and trichothiodystrophy (TTD) group A, etc. This component, XPC, plays an important role in the early steps of global genome NER, especially in damage recognition, open complex formation, and repair protein complex formation.[1]

The complex of XPC-RAD23B is the initial damage recognition factor in global genomic nucleotide excision repair (GG-NER).[3] XPC-RAD23B recognizes a wide variety of lesions that thermodynamically destabilize DNA duplexes, including UV-induced photoproducts (cyclopyrimidine dimers and 6-4 photoproducts ), adducts formed by environmental mutagens such as benzo[a]pyrene or various aromatic amines, certain oxidative endogenous lesions such as cyclopurines and adducts formed by cancer chemotherapeutic drugs such as cisplatin. The presence of XPC-RAD23B is required for assembly of the other core NER factors and progression through the NER pathway both in vitro and in vivo.[4] Although most studies have been performed with XPC-RAD23B, it is part of a trimeric complex with centrin-2, a calcium-binding protein of the calmodulin family.[4]

Clinical significance

Mutations in this gene or some other NER components result in Xeroderma pigmentosum, a rare autosomal recessive disorder characterized by increased sensitivity to sunlight with the development of carcinomas at an early age.[1]

Cancer

DNA damage appears to be the primary underlying cause of cancer,[5][6] and deficiencies in DNA repair genes likely underlie many forms of cancer.[7][8] If DNA repair is deficient, DNA damage tends to accumulate. Such excess DNA damage may increase mutations due to error-prone translesion synthesis. Excess DNA damage may also increase epigenetic alterations due to errors during DNA repair.[9][10] Such mutations and epigenetic alterations may give rise to cancer.

Reductions in expression of DNA repair genes (usually caused by epigenetic alterations such as promoter hypermethylation) are very common in cancers, and are ordinarily much more frequent than mutational defects in DNA repair genes in cancers.[11] The table below shows that XPC expression was frequently epigenetically reduced in bladder cancer and also in non-small cell lung cancer, and also shows that XPC was more frequently reduced in the more advanced stages of these cancers.

Frequency of reduced expression of XPC in cancers, with stages of cancers indicated separately
Cancer Frequency Ref.
Bladder cancer 50%[12]
Papillary urothelial neoplasm of low malignant potential35% [12]
Low grade papillary bladder cancer42% [12]
High grade papillary bladder cancer65% [12]
Non-small cell lung cancer (NSCLC) 70%[13]
NSCLC Stage I62% [13]
NSCLC Stages II-III77% [13]

While epigenetic hypermethylation of the promoter region of the XPC gene was shown to be associated with low expression of XPC,[12] another mode of epigenetic repression of XPC may also occur by over-expression of the microRNA miR-890.[14]

Interactions

XPC (gene) has been shown to interact with ABCA1,[15] CETN2[16] and XPB.[17]

References

1. ^1 2 {{cite web | title = Entrez Gene: XPC xeroderma pigmentosum, complementation group C| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=7508| accessdate = }}
2. ^{{cite web|url=http://www.omim.org/entry/278720 |accessdate=12 December 2014 |deadurl=yes }}
3. ^{{cite journal |vauthors=Sugasawa K, Ng JM, Masutani C, Iwai S, van der Spek PJ, Eker AP, Hanaoka F, Bootsma D, Hoeijmakers JH |title=Xeroderma pigmentosum group C protein complex is the initiator of global genome nucleotide excision repair |journal=Mol. Cell |volume=2 |issue=2 |pages=223–32 |year=1998 |pmid=9734359 |doi= 10.1016/s1097-2765(00)80132-x|url=}}
4. ^1 {{cite journal | vauthors = Schärer OD | title = Nucleotide excision repair in eukaryotes | journal = Cold Spring Harbor Perspectives in Biology | volume = 5 | issue = 10 | pages = a012609 | date = Oct 2013 | pmid = 24086042 | pmc = 3783044 | doi = 10.1101/cshperspect.a012609 }}
5. ^{{vcite2 journal |vauthors=Kastan MB |title=DNA damage responses: mechanisms and roles in human disease: 2007 G.H.A. Clowes Memorial Award Lecture |journal=Mol. Cancer Res. |volume=6 |issue=4 |pages=517–24 |year=2008 |pmid=18403632 |doi=10.1158/1541-7786.MCR-08-0020 |url=}}
6. ^Bernstein C, Prasad AR, Nfonsam V, Bernstein H. (2013). DNA Damage, DNA Repair and Cancer, New Research Directions in DNA Repair, Prof. Clark Chen (Ed.), {{ISBN|978-953-51-1114-6}}, InTech, http://www.intechopen.com/books/new-research-directions-in-dna-repair/dna-damage-dna-repair-and-cancer
7. ^{{cite journal |vauthors=Harper JW, Elledge SJ |title=The DNA damage response: ten years after |journal=Mol. Cell |volume=28 |issue=5 |pages=739–45 |year=2007 |pmid=18082599 |doi=10.1016/j.molcel.2007.11.015 |url=}}
8. ^{{cite journal |vauthors=Dietlein F, Reinhardt HC |title=Molecular pathways: exploiting tumor-specific molecular defects in DNA repair pathways for precision cancer therapy |journal=Clin. Cancer Res. |volume=20 |issue=23 |pages=5882–7 |year=2014 |pmid=25451105 |doi=10.1158/1078-0432.CCR-14-1165 |url=}}
9. ^{{cite journal | vauthors = O'Hagan HM, Mohammad HP, Baylin SB | title = Double strand breaks can initiate gene silencing and SIRT1-dependent onset of DNA methylation in an exogenous promoter CpG island | journal = PLoS Genetics | volume = 4 | issue = 8 | pages = e1000155 | year = 2008 | pmid = 18704159 | pmc = 2491723 | doi = 10.1371/journal.pgen.1000155 }}
10. ^{{cite journal | vauthors = Cuozzo C, Porcellini A, Angrisano T, Morano A, Lee B, Di Pardo A, Messina S, Iuliano R, Fusco A, Santillo MR, Muller MT, Chiariotti L, Gottesman ME, Avvedimento EV | title = DNA damage, homology-directed repair, and DNA methylation | journal = PLoS Genetics | volume = 3 | issue = 7 | pages = e110 | date = Jul 2007 | pmid = 17616978 | pmc = 1913100 | doi = 10.1371/journal.pgen.0030110 }}
11. ^Carol Bernstein and Harris Bernstein (2015). Epigenetic Reduction of DNA Repair in Progression to Cancer, Advances in DNA Repair, Prof. Clark Chen (Ed.), {{ISBN|978-953-51-2209-8}}, InTech, Available from: http://www.intechopen.com/books/advances-in-dna-repair/epigenetic-reduction-of-dna-repair-in-progression-to-cancer
12. ^1 2 3 4 {{cite journal |vauthors=Yang J, Xu Z, Li J, Zhang R, Zhang G, Ji H, Song B, Chen Z |title=XPC epigenetic silence coupled with p53 alteration has a significant impact on bladder cancer outcome |journal=J. Urol. |volume=184 |issue=1 |pages=336–43 |year=2010 |pmid=20488473 |doi=10.1016/j.juro.2010.03.044 |url=}}
13. ^1 2 {{cite journal |vauthors=Yeh KT, Wu YH, Lee MC, Wang L, Li CT, Chen CY, Lee H |title=XPC mRNA level may predict relapse in never-smokers with non-small cell lung cancers |journal=Ann. Surg. Oncol. |volume=19 |issue=3 |pages=734–42 |year=2012 |pmid=21861227 |doi=10.1245/s10434-011-1992-9 |url=}}
14. ^{{cite journal |vauthors=Hatano K, Kumar B, Zhang Y, Coulter JB, Hedayati M, Mears B, Ni X, Kudrolli TA, Chowdhury WH, Rodriguez R, DeWeese TL, Lupold SE |title=A functional screen identifies miRNAs that inhibit DNA repair and sensitize prostate cancer cells to ionizing radiation |journal=Nucleic Acids Res. |volume=43 |issue=8 |pages=4075–86 |year=2015 |pmid=25845598 |pmc=4417178 |doi=10.1093/nar/gkv273 |url=}}
15. ^{{cite journal | vauthors = Shimizu Y, Iwai S, Hanaoka F, Sugasawa K | title = Xeroderma pigmentosum group C protein interacts physically and functionally with thymine DNA glycosylase | language = | journal = EMBO J. | volume = 22 | issue = 1 | pages = 164–73 | date = January 2003 | pmid = 12505994 | pmc = 140069 | doi = 10.1093/emboj/cdg016 }}
16. ^{{cite journal | vauthors = Araki M, Masutani C, Takemura M, Uchida A, Sugasawa K, Kondoh J, Ohkuma Y, Hanaoka F | title = Centrosome protein centrin 2/caltractin 1 is part of the xeroderma pigmentosum group C complex that initiates global genome nucleotide excision repair | journal = J. Biol. Chem. | volume = 276 | issue = 22 | pages = 18665–72 | date = June 2001 | pmid = 11279143 | doi = 10.1074/jbc.M100855200 }}
17. ^{{cite journal | vauthors = Yokoi M, Masutani C, Maekawa T, Sugasawa K, Ohkuma Y, Hanaoka F | title = The xeroderma pigmentosum group C protein complex XPC-HR23B plays an important role in the recruitment of transcription factor IIH to damaged DNA | journal = J. Biol. Chem. | volume = 275 | issue = 13 | pages = 9870–5 | date = March 2000 | pmid = 10734143 | doi = 10.1074/jbc.275.13.9870 }}

Further reading

{{Refbegin | 2}}
  • {{cite journal | vauthors = Cleaver JE, Thompson LH, Richardson AS, States JC | title = A summary of mutations in the UV-sensitive disorders: xeroderma pigmentosum, Cockayne syndrome, and trichothiodystrophy. | journal = Hum. Mutat. | volume = 14 | issue = 1 | pages = 9–22 | year = 1999 | pmid = 10447254 | doi = 10.1002/(SICI)1098-1004(1999)14:1<9::AID-HUMU2>3.0.CO;2-6 }}
  • {{cite journal | vauthors = El-Deiry WS | title = Transactivation of repair genes by BRCA1. | journal = Cancer Biol. Ther. | volume = 1 | issue = 5 | pages = 490–1 | year = 2003 | pmid = 12496474 | doi = 10.4161/cbt.1.5.162}}
  • {{cite journal | vauthors = Sugasawa K | title = UV-induced ubiquitylation of XPC complex, the UV-DDB-ubiquitin ligase complex, and DNA repair. | journal = J. Mol. Histol. | volume = 37 | issue = 5–7 | pages = 189–202 | year = 2007 | pmid = 16858626 | doi = 10.1007/s10735-006-9044-7 }}
  • {{cite journal | vauthors = Legerski R, Peterson C | title = Expression cloning of a human DNA repair gene involved in xeroderma pigmentosum group C | journal = Nature | volume = 360 | issue = 6404 | pages = 610 | year = 1993 | pmid = 1461286 | doi = 10.1038/360610b0 }}
  • {{cite journal | vauthors = Legerski R, Peterson C | title = Expression cloning of a human DNA repair gene involved in xeroderma pigmentosum group C | journal = Nature | volume = 359 | issue = 6390 | pages = 70–3 | year = 1992 | pmid = 1522891 | doi = 10.1038/359070a0 }}
  • {{cite journal | vauthors = Legerski RJ, Liu P, Li L, Peterson CA, Zhao Y, Leach RJ, Naylor SL, Siciliano MJ | title = Assignment of xeroderma pigmentosum group C (XPC) gene to chromosome 3p25 | journal = Genomics | volume = 21 | issue = 1 | pages = 266–9 | year = 1994 | pmid = 8088800 | doi = 10.1006/geno.1994.1256 }}
  • {{cite journal | vauthors = Maruyama K, Sugano S | title = Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides | journal = Gene | volume = 138 | issue = 1–2 | pages = 171–4 | year = 1994 | pmid = 8125298 | doi = 10.1016/0378-1119(94)90802-8 }}
  • {{cite journal | vauthors = Masutani C, Sugasawa K, Yanagisawa J, Sonoyama T, Ui M, Enomoto T, Takio K, Tanaka K, van der Spek PJ, Bootsma D | title = Purification and cloning of a nucleotide excision repair complex involving the xeroderma pigmentosum group C protein and a human homologue of yeast RAD23 | journal = EMBO J. | volume = 13 | issue = 8 | pages = 1831–43 | year = 1994 | pmid = 8168482 | pmc = 395023 | doi = 10.1002/j.1460-2075.1994.tb06452.x}}
  • {{cite journal | vauthors = Li L, Bales ES, Peterson CA, Legerski RJ | title = Characterization of molecular defects in xeroderma pigmentosum group C | journal = Nat. Genet. | volume = 5 | issue = 4 | pages = 413–7 | year = 1994 | pmid = 8298653 | doi = 10.1038/ng1293-413 }}
  • {{cite journal | vauthors = Li L, Peterson C, Legerski R | title = Sequence of the mouse XPC cDNA and genomic structure of the human XPC gene | journal = Nucleic Acids Res. | volume = 24 | issue = 6 | pages = 1026–8 | year = 1996 | pmid = 8604333 | pmc = 145764 | doi = 10.1093/nar/24.6.1026 }}
  • {{cite journal | vauthors = van der Spek PJ, Eker A, Rademakers S, Visser C, Sugasawa K, Masutani C, Hanaoka F, Bootsma D, Hoeijmakers JH | title = XPC and human homologs of RAD23: intracellular localization and relationship to other nucleotide excision repair complexes | journal = Nucleic Acids Res. | volume = 24 | issue = 13 | pages = 2551–9 | year = 1996 | pmid = 8692695 | pmc = 145966 | doi = 10.1093/nar/24.13.2551 }}
  • {{cite journal | vauthors = Li L, Lu X, Peterson C, Legerski R | title = XPC interacts with both HHR23B and HHR23A in vivo | journal = Mutat. Res. | volume = 383 | issue = 3 | pages = 197–203 | year = 1997 | pmid = 9164480 | doi = 10.1016/s0921-8777(97)00002-5 }}
  • {{cite journal | vauthors = Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S | title = Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library | journal = Gene | volume = 200 | issue = 1–2 | pages = 149–56 | year = 1997 | pmid = 9373149 | doi = 10.1016/S0378-1119(97)00411-3 }}
  • {{cite journal | vauthors = Zeng L, Quilliet X, Chevallier-Lagente O, Eveno E, Sarasin A, Mezzina M | title = Retrovirus-mediated gene transfer corrects DNA repair defect of xeroderma pigmentosum cells of complementation groups A, B and C | journal = Gene Ther. | volume = 4 | issue = 10 | pages = 1077–84 | year = 1998 | pmid = 9415314 | doi = 10.1038/sj.gt.3300495 }}
  • {{cite journal | vauthors = Khan SG, Levy HL, Legerski R, Quackenbush E, Reardon JT, Emmert S, Sancar A, Li L, Schneider TD, Cleaver JE, Kraemer KH | title = Xeroderma pigmentosum group C splice mutation associated with autism and hypoglycinemia | journal = J. Invest. Dermatol. | volume = 111 | issue = 5 | pages = 791–6 | year = 1998 | pmid = 9804340 | doi = 10.1046/j.1523-1747.1998.00391.x }}
  • {{cite journal | vauthors = Yokoi M, Masutani C, Maekawa T, Sugasawa K, Ohkuma Y, Hanaoka F | title = The xeroderma pigmentosum group C protein complex XPC-HR23B plays an important role in the recruitment of transcription factor IIH to damaged DNA | journal = J. Biol. Chem. | volume = 275 | issue = 13 | pages = 9870–5 | year = 2000 | pmid = 10734143 | doi = 10.1074/jbc.275.13.9870 }}
  • {{cite journal | vauthors = Batty D, Rapic'-Otrin V, Levine AS, Wood RD | title = Stable binding of human XPC complex to irradiated DNA confers strong discrimination for damaged sites | journal = J. Mol. Biol. | volume = 300 | issue = 2 | pages = 275–90 | year = 2000 | pmid = 10873465 | doi = 10.1006/jmbi.2000.3857 }}
  • {{cite journal | vauthors = Araújo SJ, Nigg EA, Wood RD | title = Strong functional interactions of TFIIH with XPC and XPG in human DNA nucleotide excision repair, without a preassembled repairosome | journal = Mol. Cell. Biol. | volume = 21 | issue = 7 | pages = 2281–91 | year = 2001 | pmid = 11259578 | pmc = 86862 | doi = 10.1128/MCB.21.7.2281-2291.2001 }}
  • {{cite journal | vauthors = Araki M, Masutani C, Takemura M, Uchida A, Sugasawa K, Kondoh J, Ohkuma Y, Hanaoka F | title = Centrosome protein centrin 2/caltractin 1 is part of the xeroderma pigmentosum group C complex that initiates global genome nucleotide excision repair | journal = J. Biol. Chem. | volume = 276 | issue = 22 | pages = 18665–72 | year = 2001 | pmid = 11279143 | doi = 10.1074/jbc.M100855200 }}
{{Refend}}

External links

  • [https://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=xp GeneReviews/NIH/NCBI/UW entry on Xeroderma Pigmentosum]
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