XPC (xeroderma pigmentosum, complementation group C)

2001-02-01   Anne Stary  , Alain Sarasin  

Laboratory of Genetic Instability, Cancer, UPR2169 CNRS, Institut de Recherches sur le Cancer, 7, rue guy Moquet, BP 8, 94801 VILLEJUIF, France

Identity

HGNC
LOCATION
3p25.1
LOCUSID
ALIAS
RAD4,XP3,XPCC,p125
FUSION GENES

DNA/RNA

Description

17703 bp; 16 exons

Transcription

3558 b mRNA

Proteins

Description

939 amino acids

Expression

ubiquitous

Localisation

nuclear

Function

Involved in the early recognition of DNA damage present in chromatine. Two proteins have been identified and implicated in (one of) the first steps of NER, i.e. the recognition of lesions in the DNA: the XPA gene product and the XPC gene product in complex with HR23B. This XPC-HR23B complex has been implicated in DNA damage recognition, especially the cyclobutane pyrimidine dimers induced by UV-light. XPC cells have low Nucleotide Excision Repair (NER) repair capacity, but the residual repair has been shown to occur specifically in transcribed genes. It is very likely that the XPC-HR23B complex is the principal damage recognition complex i.e. essential for the recognition of DNA lesions in the genome. Binding of XPC-HR23B to a DNA lesion causes local unwinding, so that the XPA protein can bind and the whole repair machinery can be loaded onto the damaged site. The XPC-HR23B complex is only required for global genome repair. In case of transcription coupled repair when an RNA polymerase is stalled at a lesion, the DNA is unwound by the transcription complex and XPA can bind independently of XPC-HR23B complex.

Homology

MGI : Xpc (Nb 103557)

Mutations

Germinal

19 mutated sites involved in the XP group C syndrome ( XPC), 95% of these mutations (non sense, frameshift, deletion or splice site mutations) give rise to truncated proteins indicating that the XPC gene is not essential for viability

Implicated in

Entity name
Xeroderma pigmentosum XPC
Disease
predisposition to skin cancer: early skin tumours

Article Bibliography

Pubmed IDLast YearTitleAuthors
91926521997Photocarcinogenesis and inhibition of intercellular adhesion molecule 1 expression in cells of DNA-repair-defective individuals.Ahrens C et al
106024971999Persistence of p53 mutations and resistance of keratinocytes to apoptosis are associated with the increased susceptibility of mice lacking the XPC gene to UV carcinogenesis.Ananthaswamy HN et al
108734652000Stable binding of human XPC complex to irradiated DNA confers strong discrimination for damaged sites.Batty D et al
96513431998Nucleosome unfolding during DNA repair in normal and xeroderma pigmentosum (group C) human cells.Baxter BK et al
108504282000Impact of global genome repair versus transcription-coupled repair on ultraviolet carcinogenesis in hairless mice.Berg RJ et al
95409831998Defective global genome repair in XPC mice is associated with skin cancer susceptibility but not with sensitivity to UVB induced erythema and edema.Berg RJ et al
34591591986Survival of UV-irradiated mammalian cells correlates with efficient DNA repair in an essential gene.Bohr VA et al
77679571995Development of a new easy complementation assay for DNA repair deficient human syndromes using cloned repair genes.Carreau M et al
107661882000Mutations in the XPC gene in families with xeroderma pigmentosum and consequences at the cell, protein, and transcript levels.Chavanne F et al
100290601999Mutational inactivation of the xeroderma pigmentosum group C gene confers predisposition to 2-acetylaminofluorene-induced liver and lung cancer and to spontaneous testicular cancer in Trp53-/- mice.Cheo DL et al
90674111997Characterization of defective nucleotide excision repair in XPC mutant mice.Cheo DL et al
94334781997Prolonged p53 protein accumulation in trichothiodystrophy fibroblasts dependent on unrepaired pyrimidine dimers on the transcribed strands of cellular genes.Dumaz N et al
93518361997Mechanism of open complex and dual incision formation by human nucleotide excision repair factors.Evans E et al
82216751993DNA strand bias in the repair of the p53 gene in normal human and xeroderma pigmentosum group C fibroblasts.Evans MK et al
107256602000Defective nucleotide excision repair in xpc mutant mice and its association with cancer predisposition.Friedberg EC et al
108436712000Transcription-coupled and global genome repair differentially influence UV-B-induced acute skin effects and systemic immunosuppression.Garssen J et al
97666701998p53 mutations in skin and internal tumors of xeroderma pigmentosum patients belonging to the complementation group C.Giglia G et al
23425041990Selective repair of specific chromatin domains in UV-irradiated cells from xeroderma pigmentosum complementation group C.Kantor GJ et al
13838111992A re-examination of the intragenome distribution of repaired sites in proliferating xeroderma pigmentosum complementation group C fibroblasts.Kantor GJ et al
110235392000A new xeroderma pigmentosum group C poly(AT) insertion/deletion polymorphism.Khan SG et al
15228911992Expression cloning of a human DNA repair gene involved in xeroderma pigmentosum group C.Legerski R et al
80888001994Assignment of xeroderma pigmentosum group C (XPC) gene to chromosome 3p25.Legerski RJ et al
82986531993Characterization of molecular defects in xeroderma pigmentosum group C.Li L et al
86043331996Sequence of the mouse XPC cDNA and genomic structure of the human XPC gene.Li L et al
96985411998Interactions of the transcription/DNA repair factor TFIIH and XP repair proteins with DNA lesions in a cell-free repair assay.Li RY et al
93729231997Identification and characterization of XPC-binding domain of hHR23B.Masutani C et al
34775641987The localization of ultraviolet-induced excision repair in the nucleus and the distribution of repair events in higher order chromatin loops in mammalian cells.Mullenders LH et al
100965501999Differential behaviors toward ultraviolet A and B radiation of fibroblasts and keratinocytes from normal and DNA-repair-deficient patients.Otto AI et al
29112721989Chromatin and nucleolar changes in Xeroderma pigmentosum cells resemble aging-related nuclear events.Puvion-Dutilleul F et al
95068921997Retroviral-mediated correction of DNA repair defect in xeroderma pigmentosum cells is associated with recovery of catalase activity.Quilliet X et al
87026341996Overproduction, purification, and characterization of the XPC subunit of the human DNA repair excision nuclease.Reardon JT et al
107491252000Genotype-specific Trp53 mutational analysis in ultraviolet B radiation-induced skin cancers in Xpc and Xpc Trp53 mutant mice.Reis AM et al
111211282000Clinical, cellular, and molecular features of an Israeli xeroderma pigmentosum family with a frameshift mutation in the XPC gene: sun protection prolongs life.Slor H et al
97343591998Xeroderma pigmentosum group C protein complex is the initiator of global genome nucleotide excision repair.Sugasawa K et al
23088421990The residual repair capacity of xeroderma pigmentosum complementation group C fibroblasts is highly specific for transcriptionally active DNA.Venema J et al
30005761986Deficiency in the catalase activity of xeroderma pigmentosum cell and simian virus 40-transformed human cell extracts.Vuillaume M et al
103734921999Order of assembly of human DNA repair excision nuclease.Wakasugi M et al
86750091996The XPB and XPD DNA helicases are components of the p53-mediated apoptosis pathway.Wang XW et al
110426912000Age-dependent spontaneous mutagenesis in Xpc mice defective in nucleotide excision repair.Wijnhoven SW et al
13721041992UV-induced base substitution mutations in a shuttle vector plasmid propagated in group C xeroderma pigmentosum cells.Yagi T et al
80845821994U.v.-induced nuclear accumulation of p53 is evoked through DNA damage of actively transcribed genes independent of the cell cycle.Yamaizumi M et al
107341432000The xeroderma pigmentosum group C protein complex XPC-HR23B plays an important role in the recruitment of transcription factor IIH to damaged DNA.Yokoi M et al
94153141997Retrovirus-mediated gene transfer corrects DNA repair defect of xeroderma pigmentosum cells of complementation groups A, B and C.Zeng L et al
101979771999Molecular mechanism of nucleotide excision repair.de Laat WL et al
78353461995Transcription-coupled repair removes both cyclobutane pyrimidine dimers and 6-4 photoproducts with equal efficiency and in a sequential way from transcribed DNA in xeroderma pigmentosum group C fibroblasts.van Hoffen A et al
110058362000Differential role of transcription-coupled repair in UVB-induced G2 arrest and apoptosis in mouse epidermis.van Oosten M et al
86926951996XPC and human homologs of RAD23: intracellular localization and relationship to other nucleotide excision repair complexes.van der Spek PJ et al

Other Information

Locus ID:

NCBI: 7508
MIM: 613208
HGNC: 12816
Ensembl: ENSG00000154767

Variants:

dbSNP: 7508
ClinVar: 7508
TCGA: ENSG00000154767
COSMIC: XPC

RNA/Proteins

Gene IDTranscript IDUniprot
ENSG00000154767ENST00000285021Q01831
ENSG00000154767ENST00000285021X5DRB1
ENSG00000154767ENST00000476581Q01831
ENSG00000154767ENST00000511155E7EUB5

Expression (GTEx)

0
10
20
30
40
50
60
70
80
90

Pathways

PathwaySourceExternal ID
Nucleotide excision repairKEGGko03420
Nucleotide excision repairKEGGhsa03420
Metabolism of proteinsREACTOMER-HSA-392499
Post-translational protein modificationREACTOMER-HSA-597592
SUMOylationREACTOMER-HSA-2990846
SUMO E3 ligases SUMOylate target proteinsREACTOMER-HSA-3108232
SUMOylation of DNA damage response and repair proteinsREACTOMER-HSA-3108214
DNA RepairREACTOMER-HSA-73894
Nucleotide Excision RepairREACTOMER-HSA-5696398
Global Genome Nucleotide Excision Repair (GG-NER)REACTOMER-HSA-5696399
DNA Damage Recognition in GG-NERREACTOMER-HSA-5696394
Formation of Incision Complex in GG-NERREACTOMER-HSA-5696395

Protein levels (Protein atlas)

Not detected
Low
Medium
High

PharmGKB

Entity IDNameTypeEvidenceAssociationPKPDPMIDs
PA164713176Platinum compoundsChemicalClinicalAnnotationassociatedPD28791697
PA166124386gastrointestinal toxicityDiseaseClinicalAnnotationassociatedPD28791697
PA443512Urinary Bladder NeoplasmsDiseaseClinicalAnnotationassociatedPD19434073, 21047201
PA443622Carcinoma, Non-Small-Cell LungDiseaseClinicalAnnotationassociatedPD28791697
PA444395Hematologic DiseasesDiseaseClinicalAnnotationassociatedPD28791697
PA444773LeukopeniaDiseaseClinicalAnnotationassociatedPD28791697
PA445062NeoplasmsDiseaseClinicalAnnotationassociatedPD19434073, 21047201
PA445601OsteosarcomaDiseaseClinicalAnnotationassociatedPD19434073, 21047201
PA445828Testicular NeoplasmsDiseaseClinicalAnnotationassociatedPD19434073, 21047201
PA449014cisplatinChemicalClinicalAnnotationassociatedPD19434073, 21047201

References

Pubmed IDYearTitleCitations
382857842024Genetic Polymorphisms of XPC, XPD, XPG Genes and their Association with Radiotherapy Induced Toxicity among Head and Neck Cancer Patients: A Hospital Based Study from Maharashtra.0
384792792024Relationship between ERCC1 and XPC polymorphisms and the susceptibility to head and neck carcinoma: A systematic review, meta-analysis, and trial sequential analysis.1
382857842024Genetic Polymorphisms of XPC, XPD, XPG Genes and their Association with Radiotherapy Induced Toxicity among Head and Neck Cancer Patients: A Hospital Based Study from Maharashtra.0
384792792024Relationship between ERCC1 and XPC polymorphisms and the susceptibility to head and neck carcinoma: A systematic review, meta-analysis, and trial sequential analysis.1
368778662023Regulation of XPC Binding Dynamics and Global Nucleotide Excision Repair by p63 and Vitamin D Receptor.0
368906382023Structural modeling and analyses of genetic variations in the human XPC nucleotide excision repair protein.0
370766182023Lesion recognition by XPC, TFIIH and XPA in DNA excision repair.10
375102552023A Significant Increasing Risk Association between Cigarette Smoking and XPA and XPC Genes Polymorphisms.0
368778662023Regulation of XPC Binding Dynamics and Global Nucleotide Excision Repair by p63 and Vitamin D Receptor.0
368906382023Structural modeling and analyses of genetic variations in the human XPC nucleotide excision repair protein.0
370766182023Lesion recognition by XPC, TFIIH and XPA in DNA excision repair.10
375102552023A Significant Increasing Risk Association between Cigarette Smoking and XPA and XPC Genes Polymorphisms.0
345441752022Loss of Function Variants in the XPC Causes Severe Xeroderma Pigmentosum in Three Large Consanguineous Families.0
359910472022Joint effects of polycyclic aromatic hydrocarbons, smoking, and XPC polymorphisms on damage in exon 2 of KRAS gene among young coke oven workers.0
345441752022Loss of Function Variants in the XPC Causes Severe Xeroderma Pigmentosum in Three Large Consanguineous Families.0

Citation

Anne Stary ; Alain Sarasin

XPC (xeroderma pigmentosum, complementation group C)

Atlas Genet Cytogenet Oncol Haematol. 2001-02-01

Online version: http://atlasgeneticsoncology.org/gene/122/js/lib/favicon/css/template-card.css