XPA xeroderma pigmentosum, complementation group A)
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
DNA/RNA
Description
human xeroderma pigmentosum group A 25kbp, six exons, 2 polyadenylation signals
Transcription
1377 b mRNA; suggestion of 1 major transcript; promoter G+C rich (73%); one CAAT box and no TATA box.
Proteins
Description
273 amino acids, 31 kDa. DNA excision repair protein. The functional domain for damaged DNA recognition contains a zinc-finger motif with 4 cysteine residues : Cys-X2-Cys-X17-Cys-X2-Cys motif and a glutamic acid cluster encoded by Exon 2. The nuclear localization signal is located in Exon 1.
Expression
ubiquitous
Localisation
nuclear
Function
Initiates DNA repair by binding to damaged sites with various affinities, depending upon the chemical structure of the lesion
Two proteins have been identified and implicated in (one of) the first steps of Nucleotide Excision Repair (NER), i.e. the recognition of lesions in the DNA: the XPA gene product and the XPC gene product. Cells from XPA patients are extremely sensitive to UV and have very low nucleotide excision repair activity. In vitro the XPA protein binds preferentially to damaged DNA compared to nondamaged DNA. The XPA protein binds to replication protein A (RPA) which enhances the affinity of XPA for damaged DNA and is essential for NER. The XPA protein has been shown to bind to ERCC1 and TFIIH. It is possible that the complex XPA/RPA may tell to the repair machinery which strand contained the damage and therefore should be eliminated.
Two proteins have been identified and implicated in (one of) the first steps of Nucleotide Excision Repair (NER), i.e. the recognition of lesions in the DNA: the XPA gene product and the XPC gene product. Cells from XPA patients are extremely sensitive to UV and have very low nucleotide excision repair activity. In vitro the XPA protein binds preferentially to damaged DNA compared to nondamaged DNA. The XPA protein binds to replication protein A (RPA) which enhances the affinity of XPA for damaged DNA and is essential for NER. The XPA protein has been shown to bind to ERCC1 and TFIIH. It is possible that the complex XPA/RPA may tell to the repair machinery which strand contained the damage and therefore should be eliminated.
Homology
Xpac (FlyBase ID) ; Xpa (MGI)
Mutations
Germinal
13 nucleotide substitutions and 5 small insertion/deletion in patients
Implicated in
Entity name
Disease
predisposition to skin cancer: early skin tumours ( basal cell carcinoma, squamous cell carcinoma and melanoma); early internal tumours
Article Bibliography
| Pubmed ID | Last Year | Title | Authors |
|---|
Other Information
Locus ID:
NCBI: 7507
MIM: 611153
HGNC: 12814
Ensembl: ENSG00000136936
Variants:
dbSNP: 7507
ClinVar: 7507
TCGA: ENSG00000136936
COSMIC: XPA
RNA/Proteins
| Gene ID | Transcript ID | Uniprot |
|---|---|---|
| ENSG00000136936 | ENST00000375128 | P23025 |
| ENSG00000136936 | ENST00000462523 | F2Z2T2 |
Expression (GTEx)
Pathways
Protein levels (Protein atlas)
PharmGKB
| Entity ID | Name | Type | Evidence | Association | PK | PD | PMIDs |
|---|---|---|---|---|---|---|---|
| PA164713176 | Platinum compounds | Chemical | ClinicalAnnotation | associated | PD | 25069034 | |
| PA443622 | Carcinoma, Non-Small-Cell Lung | Disease | ClinicalAnnotation | associated | PD | 25069034 |
References
| Pubmed ID | Year | Title | Citations |
|---|---|---|---|
| 36893274 | 2023 | A disease-associated XPA allele interferes with TFIIH binding and primarily affects transcription-coupled nucleotide excision repair. | 2 |
| 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 |
| 36893274 | 2023 | A disease-associated XPA allele interferes with TFIIH binding and primarily affects transcription-coupled nucleotide excision repair. | 2 |
| 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 |
| 34883264 | 2022 | XPA is susceptible to proteolytic cleavage by cathepsin L during lysis of quiescent cells. | 2 |
| 35084844 | 2022 | Probing Protein-DNA Conformational Dynamics in DNA Damage Recognition: Xeroderma Pigmentosum Group A Stabilizes the Damaged DNA-RPA14 Complex by Controlling Conformational Fluctuation Dynamics. | 0 |
| 35216341 | 2022 | Nucleotide Excision Repair Pathway Activity Is Inhibited by Airborne Particulate Matter (PM(10)) through XPA Deregulation in Lung Epithelial Cells. | 1 |
| 35536165 | 2022 | XPA Enhances Temozolomide Resistance of Glioblastoma Cells by Promoting Nucleotide Excision Repair. | 3 |
| 36232946 | 2022 | Homozygous CRISPR/Cas9 Knockout Generated a Novel Functionally Active Exon 1 Skipping XPA Variant in Melanoma Cells. | 1 |
| 34883264 | 2022 | XPA is susceptible to proteolytic cleavage by cathepsin L during lysis of quiescent cells. | 2 |
| 35084844 | 2022 | Probing Protein-DNA Conformational Dynamics in DNA Damage Recognition: Xeroderma Pigmentosum Group A Stabilizes the Damaged DNA-RPA14 Complex by Controlling Conformational Fluctuation Dynamics. | 0 |
| 35216341 | 2022 | Nucleotide Excision Repair Pathway Activity Is Inhibited by Airborne Particulate Matter (PM(10)) through XPA Deregulation in Lung Epithelial Cells. | 1 |
| 35536165 | 2022 | XPA Enhances Temozolomide Resistance of Glioblastoma Cells by Promoting Nucleotide Excision Repair. | 3 |
Citation
Anne Stary ; Alain Sarasin
XPA xeroderma pigmentosum, complementation group A)
Atlas Genet Cytogenet Oncol Haematol. 2001-02-01
Online version: http://atlasgeneticsoncology.org/gene/104/xpa
