XPC (xeroderma pigmentosum, complementation group C)

2001-02-01 Anne Stary , Alain Sarasin Affiliation

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

Identity

HGNC

XPC

LOCATION

3p25.1

LOCUSID

7508

ALIAS

RAD4,XP3,XPCC,p125

FUSION GENES

Show Gene Fusions

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 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)

Adipose - Subcutaneous

Adipose - Visceral

Adrenal Gland

Artery - Aorta

Artery - Tibial

Bladder

Brain - Amygdala

Brain - Anterior cingulate cortex

Brain - Caudate

Brain - Cerebellar Hemisphere

Brain - Cerebellum

Brain - Cortex

Brain - Frontal Cortex

Brain - Hippocampus

Brain - Hypothalamus

Brain - Nucleus accumbens

Brain - Putamen

Brain - Spinal cord

Brain - Substantia nigra

Breast - Mammary Tissue

Cells - Cultured fibroblasts

Cells - EBV - transformed lymphocytes

Cervix - Ectocervix

Cervix - Endocervix

Colon - Sigmoid

Colon - Transverse

Esophagus - Gastroesophageal Junction

Esophagus - Mucosa

Esophagus - Muscularis

Fallopian Tube

Heart - Atrial Appendage

Heart - Left Ventricle

Kidney - Cortex

Kidney - Medulla

Liver

Lung

Minor Salivary Gland

Muscle - Skeletal

Nerve - Tibial

Ovary

Pancreas

Pituitary

Prostate

Skin - Not Sun Exposed

Skin - Sun Exposed

Small Intestine - Terminal Ileum

Spleen

Stomach

Testis

Thyroid

Uterus

Vagina

Whole Blood

Pathways

Pathway	Source	External ID
Nucleotide excision repair	KEGG	ko03420
Nucleotide excision repair	KEGG	hsa03420
Metabolism of proteins	REACTOME	R-HSA-392499
Post-translational protein modification	REACTOME	R-HSA-597592
SUMOylation	REACTOME	R-HSA-2990846
SUMO E3 ligases SUMOylate target proteins	REACTOME	R-HSA-3108232
SUMOylation of DNA damage response and repair proteins	REACTOME	R-HSA-3108214
DNA Repair	REACTOME	R-HSA-73894
Nucleotide Excision Repair	REACTOME	R-HSA-5696398
Global Genome Nucleotide Excision Repair (GG-NER)	REACTOME	R-HSA-5696399
DNA Damage Recognition in GG-NER	REACTOME	R-HSA-5696394
Formation of Incision Complex in GG-NER	REACTOME	R-HSA-5696395

Protein levels (Protein atlas)

Not detected

Low

Medium

High

PharmGKB

Entity ID	Name	Type	Evidence	Association	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/css/js/lib/favicon/favicon-16x16.png