XPC (xeroderma pigmentosum, complementation group C)
2001-02-01 Anne Stary , Alain Sarasin AffiliationLaboratory 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
Disease
predisposition to skin cancer: early skin tumours
Article Bibliography
| Pubmed ID | Last Year | Title | Authors |
|---|---|---|---|
| 9192652 | 1997 | Photocarcinogenesis and inhibition of intercellular adhesion molecule 1 expression in cells of DNA-repair-defective individuals. | Ahrens C et al |
| 10602497 | 1999 | Persistence 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 |
| 10873465 | 2000 | Stable binding of human XPC complex to irradiated DNA confers strong discrimination for damaged sites. | Batty D et al |
| 9651343 | 1998 | Nucleosome unfolding during DNA repair in normal and xeroderma pigmentosum (group C) human cells. | Baxter BK et al |
| 10850428 | 2000 | Impact of global genome repair versus transcription-coupled repair on ultraviolet carcinogenesis in hairless mice. | Berg RJ et al |
| 9540983 | 1998 | Defective 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 |
| 3459159 | 1986 | Survival of UV-irradiated mammalian cells correlates with efficient DNA repair in an essential gene. | Bohr VA et al |
| 7767957 | 1995 | Development of a new easy complementation assay for DNA repair deficient human syndromes using cloned repair genes. | Carreau M et al |
| 10766188 | 2000 | Mutations in the XPC gene in families with xeroderma pigmentosum and consequences at the cell, protein, and transcript levels. | Chavanne F et al |
| 10029060 | 1999 | Mutational 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 |
| 9067411 | 1997 | Characterization of defective nucleotide excision repair in XPC mutant mice. | Cheo DL et al |
| 9433478 | 1997 | Prolonged p53 protein accumulation in trichothiodystrophy fibroblasts dependent on unrepaired pyrimidine dimers on the transcribed strands of cellular genes. | Dumaz N et al |
| 9351836 | 1997 | Mechanism of open complex and dual incision formation by human nucleotide excision repair factors. | Evans E et al |
| 8221675 | 1993 | DNA strand bias in the repair of the p53 gene in normal human and xeroderma pigmentosum group C fibroblasts. | Evans MK et al |
| 10725660 | 2000 | Defective nucleotide excision repair in xpc mutant mice and its association with cancer predisposition. | Friedberg EC et al |
| 10843671 | 2000 | Transcription-coupled and global genome repair differentially influence UV-B-induced acute skin effects and systemic immunosuppression. | Garssen J et al |
| 9766670 | 1998 | p53 mutations in skin and internal tumors of xeroderma pigmentosum patients belonging to the complementation group C. | Giglia G et al |
| 2342504 | 1990 | Selective repair of specific chromatin domains in UV-irradiated cells from xeroderma pigmentosum complementation group C. | Kantor GJ et al |
| 1383811 | 1992 | A re-examination of the intragenome distribution of repaired sites in proliferating xeroderma pigmentosum complementation group C fibroblasts. | Kantor GJ et al |
| 11023539 | 2000 | A new xeroderma pigmentosum group C poly(AT) insertion/deletion polymorphism. | Khan SG et al |
| 1522891 | 1992 | Expression cloning of a human DNA repair gene involved in xeroderma pigmentosum group C. | Legerski R et al |
| 8088800 | 1994 | Assignment of xeroderma pigmentosum group C (XPC) gene to chromosome 3p25. | Legerski RJ et al |
| 8298653 | 1993 | Characterization of molecular defects in xeroderma pigmentosum group C. | Li L et al |
| 8604333 | 1996 | Sequence of the mouse XPC cDNA and genomic structure of the human XPC gene. | Li L et al |
| 9698541 | 1998 | Interactions of the transcription/DNA repair factor TFIIH and XP repair proteins with DNA lesions in a cell-free repair assay. | Li RY et al |
| 9372923 | 1997 | Identification and characterization of XPC-binding domain of hHR23B. | Masutani C et al |
| 3477564 | 1987 | The 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 |
| 10096550 | 1999 | Differential behaviors toward ultraviolet A and B radiation of fibroblasts and keratinocytes from normal and DNA-repair-deficient patients. | Otto AI et al |
| 2911272 | 1989 | Chromatin and nucleolar changes in Xeroderma pigmentosum cells resemble aging-related nuclear events. | Puvion-Dutilleul F et al |
| 9506892 | 1997 | Retroviral-mediated correction of DNA repair defect in xeroderma pigmentosum cells is associated with recovery of catalase activity. | Quilliet X et al |
| 8702634 | 1996 | Overproduction, purification, and characterization of the XPC subunit of the human DNA repair excision nuclease. | Reardon JT et al |
| 10749125 | 2000 | Genotype-specific Trp53 mutational analysis in ultraviolet B radiation-induced skin cancers in Xpc and Xpc Trp53 mutant mice. | Reis AM et al |
| 11121128 | 2000 | Clinical, 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 |
| 9734359 | 1998 | Xeroderma pigmentosum group C protein complex is the initiator of global genome nucleotide excision repair. | Sugasawa K et al |
| 2308842 | 1990 | The residual repair capacity of xeroderma pigmentosum complementation group C fibroblasts is highly specific for transcriptionally active DNA. | Venema J et al |
| 3000576 | 1986 | Deficiency in the catalase activity of xeroderma pigmentosum cell and simian virus 40-transformed human cell extracts. | Vuillaume M et al |
| 10373492 | 1999 | Order of assembly of human DNA repair excision nuclease. | Wakasugi M et al |
| 8675009 | 1996 | The XPB and XPD DNA helicases are components of the p53-mediated apoptosis pathway. | Wang XW et al |
| 11042691 | 2000 | Age-dependent spontaneous mutagenesis in Xpc mice defective in nucleotide excision repair. | Wijnhoven SW et al |
| 1372104 | 1992 | UV-induced base substitution mutations in a shuttle vector plasmid propagated in group C xeroderma pigmentosum cells. | Yagi T et al |
| 8084582 | 1994 | U.v.-induced nuclear accumulation of p53 is evoked through DNA damage of actively transcribed genes independent of the cell cycle. | Yamaizumi M et al |
| 10734143 | 2000 | The 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 |
| 9415314 | 1997 | Retrovirus-mediated gene transfer corrects DNA repair defect of xeroderma pigmentosum cells of complementation groups A, B and C. | Zeng L et al |
| 10197977 | 1999 | Molecular mechanism of nucleotide excision repair. | de Laat WL et al |
| 7835346 | 1995 | Transcription-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 |
| 11005836 | 2000 | Differential role of transcription-coupled repair in UVB-induced G2 arrest and apoptosis in mouse epidermis. | van Oosten M et al |
| 8692695 | 1996 | XPC 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 ID | Transcript ID | Uniprot |
|---|---|---|
| ENSG00000154767 | ENST00000285021 | Q01831 |
| ENSG00000154767 | ENST00000285021 | X5DRB1 |
| ENSG00000154767 | ENST00000476581 | Q01831 |
| ENSG00000154767 | ENST00000511155 | E7EUB5 |
Expression (GTEx)
Pathways
Protein levels (Protein atlas)
PharmGKB
| Entity ID | Name | Type | Evidence | Association | PK | PD | PMIDs |
|---|---|---|---|---|---|---|---|
| PA164713176 | Platinum compounds | Chemical | ClinicalAnnotation | associated | PD | 28791697 | |
| PA166124386 | gastrointestinal toxicity | Disease | ClinicalAnnotation | associated | PD | 28791697 | |
| PA443512 | Urinary Bladder Neoplasms | Disease | ClinicalAnnotation | associated | PD | 19434073, 21047201 | |
| PA443622 | Carcinoma, Non-Small-Cell Lung | Disease | ClinicalAnnotation | associated | PD | 28791697 | |
| PA444395 | Hematologic Diseases | Disease | ClinicalAnnotation | associated | PD | 28791697 | |
| PA444773 | Leukopenia | Disease | ClinicalAnnotation | associated | PD | 28791697 | |
| PA445062 | Neoplasms | Disease | ClinicalAnnotation | associated | PD | 19434073, 21047201 | |
| PA445601 | Osteosarcoma | Disease | ClinicalAnnotation | associated | PD | 19434073, 21047201 | |
| PA445828 | Testicular Neoplasms | Disease | ClinicalAnnotation | associated | PD | 19434073, 21047201 | |
| PA449014 | cisplatin | Chemical | ClinicalAnnotation | associated | PD | 19434073, 21047201 |
References
| Pubmed ID | Year | Title | Citations |
|---|---|---|---|
| 38285784 | 2024 | Genetic 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 |
| 38479279 | 2024 | Relationship between ERCC1 and XPC polymorphisms and the susceptibility to head and neck carcinoma: A systematic review, meta-analysis, and trial sequential analysis. | 1 |
| 38285784 | 2024 | Genetic 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 |
| 38479279 | 2024 | Relationship between ERCC1 and XPC polymorphisms and the susceptibility to head and neck carcinoma: A systematic review, meta-analysis, and trial sequential analysis. | 1 |
| 36877866 | 2023 | Regulation of XPC Binding Dynamics and Global Nucleotide Excision Repair by p63 and Vitamin D Receptor. | 0 |
| 36890638 | 2023 | Structural modeling and analyses of genetic variations in the human XPC nucleotide excision repair protein. | 0 |
| 37076618 | 2023 | Lesion recognition by XPC, TFIIH and XPA in DNA excision repair. | 10 |
| 37510255 | 2023 | A Significant Increasing Risk Association between Cigarette Smoking and XPA and XPC Genes Polymorphisms. | 0 |
| 36877866 | 2023 | Regulation of XPC Binding Dynamics and Global Nucleotide Excision Repair by p63 and Vitamin D Receptor. | 0 |
| 36890638 | 2023 | Structural modeling and analyses of genetic variations in the human XPC nucleotide excision repair protein. | 0 |
| 37076618 | 2023 | Lesion recognition by XPC, TFIIH and XPA in DNA excision repair. | 10 |
| 37510255 | 2023 | A Significant Increasing Risk Association between Cigarette Smoking and XPA and XPC Genes Polymorphisms. | 0 |
| 34544175 | 2022 | Loss of Function Variants in the XPC Causes Severe Xeroderma Pigmentosum in Three Large Consanguineous Families. | 0 |
| 35991047 | 2022 | Joint effects of polycyclic aromatic hydrocarbons, smoking, and XPC polymorphisms on damage in exon 2 of KRAS gene among young coke oven workers. | 0 |
| 34544175 | 2022 | Loss 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/xpc
