Description:
XERODERMA PIGMENTOSUM, COMPLEMENTATION GROUP A; XPA
XPA, DNA DAMAGE RECOGNITION AND REPAIR FACTOR; XPA
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Repository
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NIGMS Human Genetic Cell Repository
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| Subcollection |
Heritable Diseases |
| Class |
Disorders of Nucleotide and Nucleic Acid Metabolism |
| Class |
Repair Defective and Chromosomal Instability Syndromes |
| Alternate IDs |
GM17051 [XERODERMA PIGMENTOSUM, COMPLEMENTATION GROUP A; XPA] |
| Quantity |
25 µg |
| Quantitation Method |
Please see our FAQ |
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Biopsy Source
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Peripheral vein
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Cell Type
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B-Lymphocyte
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Tissue Type
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Blood
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Transformant
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Epstein-Barr Virus
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Sample Source
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DNA from LCL
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Race
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Asian
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Ethnicity
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JAPANESE
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Family Member
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1
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Relation to Proband
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proband
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Confirmation
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Clinical summary/Case history
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Species
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Homo sapiens
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Common Name
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Human
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Remarks
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| IDENTIFICATION OF SPECIES OF ORIGIN |
Species of Origin Confirmed by Nucleoside Phosphorylase, Glucose-6-Phosphate Dehydrogenase, and Lactate Dehydrogenase Isoenzyme Electrophoresis |
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| DNA METHYLATION |
Sano et al (Mutation Res 217:141-151,1989) examined DNA methylation in normal and Xeroderma pigmentosum cell lines. The amount of 5-methylcytosine in DNA from XP cell lines was on average about 70% of that in DNA from normal controls. The value observed for this XP cell line was 80%. Southern hybridization analysis showed that the HLA-DRa gene in XP B-lymphoblasts was differently methylated from normals, but its expression was apparently unaffected. The methylation of dihydrofolate reductase, a housekeeping gene, was the same as in controls. |
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| GENE MAPPING & DOSAGE STUDIES - Y CHROMOSOME |
PCR analysis of DNA from this cell culture gave a negative result with a primer for Yq11, DYS227. |
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| Gene |
XPA |
| Chromosomal Location |
9q22.3-q31 |
| Allelic Variant 1 |
278700.0001; XERODERMA PIGMENTOSUM, TYPE A |
| Identified Mutation |
3-PRIME SPLICE SITE, INTRON 3; Tanaka et al. [Nature 348: 73-76 (1990)] found that most Japanese patients with type A xeroderma pigmentosum had a G-to-C transversion at the 3-prime splice acceptor site of intron 3 of the XPAC gene. Satokata et al. [Proc. Nat. Acad. Sci. 87: 9908-9912, (1990)] found that the single base substitution abolished the canonical 3-prime splice site and created 2 abnormally spliced mRNA forms. The larger form was identical with normal mRNA except for a dinucleotide deletion at the 5-prime end of exon 4. This deletion resulted in a frameshift with premature termination of translation in exon 4. The smaller form had a deletion of the entire exon 3 and the dinucleotide at the 5-prime end of exon 4. A single base substitution creates a new cleavage site for the restriction endonuclease AlwNI. Using the AlwNI RFLP, Satokata et al. [Proc. Nat. Acad. Sci. 87: 9908-9912 (1990)] found that 16 of 21 unrelated Japanese patients with XP were homozygous and 4 were heterozygous for this mutation. However, 11 Caucasians and 2 blacks with group A XP did not have this mutant allele. Kore-eda et al. [Arch. Derm. 128: 971-974 (1992)] demonstrated the usefulness of the polymerase chain reaction (PCR) followed by search for the AlwNI RFLP in the diagnosis of XPA. Cleaver et al. [Hum. Molec. Genet. 4: 1685-1687 (1995)] stated that homozygosity for a G-to-C transversion at the 3-prime acceptor site of intron III/exon IV represents 80 to 90% of Japanese patients with XPA. |
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| Gene |
XPA |
| Chromosomal Location |
9q22.3-q31 |
| Allelic Variant 2 |
278700.0001; XERODERMA PIGMENTOSUM, TYPE A |
| Identified Mutation |
3-PRIME SPLICE SITE, INTRON 3; Tanaka et al. [Nature 348: 73-76 (1990)] found that most Japanese patients with type A xeroderma pigmentosum had a G-to-C transversion at the 3-prime splice acceptor site of intron 3 of the XPAC gene. Satokata et al. [Proc. Nat. Acad. Sci. 87: 9908-9912, (1990)] found that the single base substitution abolished the canonical 3-prime splice site and created 2 abnormally spliced mRNA forms. The larger form was identical with normal mRNA except for a dinucleotide deletion at the 5-prime end of exon 4. This deletion resulted in a frameshift with premature termination of translation in exon 4. The smaller form had a deletion of the entire exon 3 and the dinucleotide at the 5-prime end of exon 4. A single base substitution creates a new cleavage site for the restriction endonuclease AlwNI. Using the AlwNI RFLP, Satokata et al. [Proc. Nat. Acad. Sci. 87: 9908-9912 (1990)] found that 16 of 21 unrelated Japanese patients with XP were homozygous and 4 were heterozygous for this mutation. However, 11 Caucasians and 2 blacks with group A XP did not have this mutant allele. Kore-eda et al. [Arch. Derm. 128: 971-974 (1992)] demonstrated the usefulness of the polymerase chain reaction (PCR) followed by search for the AlwNI RFLP in the diagnosis of XPA. Cleaver et al. [Hum. Molec. Genet. 4: 1685-1687 (1995)] stated that homozygosity for a G-to-C transversion at the 3-prime acceptor site of intron III/exon IV represents 80 to 90% of Japanese patients with XPA. |
| Remarks |
Japanese; XP20S; severe XP; mental retardation; gait disturbance; see GM04312 SV40 Transformed Fibroblast; < 2% of normal UV induced unscheduled DNA synthesis in fibroblasts; similarly affected sister is GM04314 (Fibroblast); donor subject is homozygous for the G-to-C transversion at the 3-prime splice acceptor site of intron 3 of the XPA gene, abolishing the canonical 3-prime splice site and creating two abnormally spliced mRNA forms. |
| Stevens EV, Nishizuka S, Antony S, Reimers M, Varma S, Young L, Munson PJ, Weinstein JN, Kohn EC, Pommier Y, Predicting cisplatin and trabectedin drug sensitivity in ovarian and colon cancers Molecular cancer therapeutics7:10-8 2008 |
| PubMed ID: 18187810 |
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| McCulloch SD, Gu L, Li GM, Nick-dependent and -independent processing of large DNA loops in human cells. J Biol Chem278(50):50803-9 2003 |
| PubMed ID: 14522965 |
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| Li L, Peterson CA, Lu X, Wei P, Legerski RJ, Interstrand cross-links induce DNA synthesis in damaged and undamaged plasmids in mammalian cell extracts Molecular and cellular biology19:5619-30 1999 |
| PubMed ID: 10409751 |
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| O'Driscoll M, Macpherson P, Xu YZ, Karran P, The cytotoxicity of DNA carboxymethylation and methylation by the model carboxymethylating agent azaserine in human cells. Carcinogenesis20:1855-62 1999 |
| PubMed ID: 10469634 |
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| Sturgis EM, Clayman GL, Guan Y, Guo Z, Wei Q, DNA repair in lymphoblastoid cell lines from patients with head and neck cancer. Arch Otolaryngol Head Neck Surg125:185-90 1999 |
| PubMed ID: 10037285 |
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| Rapic Otrin V, Kuraoka I, Nardo T, McLenigan M, Eker AP, Stefanini M, Levine
AS, Wood RD, Relationship of the xeroderma pigmentosum group E DNA repair defect to the chromatin and DNA binding proteins UV-DDB and replication protein A. Mol Cell Biol18(6):3182-90 1998 |
| PubMed ID: 9584159 |
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| Bessho T, Sancar A, Thompson LH, Thelen MP, Reconstitution of human excision nuclease with recombinant XPF-ERCC1 complex. J Biol Chem272:3833-7 1997 |
| PubMed ID: 9013642 |
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| Reardon JT, Bessho T, Kung HC, Bolton PH, Sancar A, In vitro repair of oxidative DNA damage by human nucleotide excision repair system: possible explanation for neurodegeneration in xeroderma pigmentosum patients. Proc Natl Acad Sci U S A94:9463-8 1997 |
| PubMed ID: 9256505 |
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| Cheng L, Bucana CD, Wei Q, Fluorescence in situ hybridization method for measuring transfection efficiency. Biotechniques21(3):486-91 1996 |
| PubMed ID: 8879589 |
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| Li L, Peterson CA, Lu X, Legerski RJ, Mutations in XPA that prevent association with ERCC1 are defective in nucleotide excision repair. Mol Cell Biol15:1993-8 1995 |
| PubMed ID: 7891694 |
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| Matsunaga T, Mu D, Park CH, Reardon JT, Sancar A, Human DNA repair excision nuclease. Analysis of the roles of the subunits involved in dual incisions by using anti-XPG and anti-ERCC1 antibodies. J Biol Chem270:20862-9 1995 |
| PubMed ID: 7657672 |
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| Vilpo JA, Vilpo LM, Szymkowski DE, O'Donovan A, Wood RD, An XPG DNA repair defect causing mutagen hypersensitivity in mouse leukemia L1210 cells. Mol Cell Biol15:290-7 1995 |
| PubMed ID: 7799936 |
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| Park CH, Sancar A, Formation of a ternary complex by human XPA, ERCC1, and ERCC4(XPF) excision repair proteins. Proc Natl Acad Sci U S A91:5017-21 1994 |
| PubMed ID: 8197175 |
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| Reardon JT, Thompson LH, Sancar A, Excision repair in man and the molecular basis of xeroderma pigmentosum syndrome. Cold Spring Harb Symp Quant Biol58:605-17 1993 |
| PubMed ID: 7956075 |
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| Calsou P, Frit P, Salles B, Repair synthesis by human cell extracts in cisplatin-damaged DNA is preferentially determined by minor adducts. Nucleic Acids Res20:6363-8 1992 |
| PubMed ID: 1475197 |
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| Satokata I, Tanaka K, Miura N, Narita M, Mimaki T, Satoh Y, Kondo S, Okada Y, Three nonsense mutations responsible for group A xeroderma pigmentosum. Mutat Res273:193-202 1992 |
| PubMed ID: 1372102 |
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| Satokata I, Tanaka K, Yuba S, Okada Y, Identification of splicing mutations of the last nucleotides of exons, a nonsense mutation, and a missense mutation of the XPAC gene as causes of group A xeroderma pigmentosum. Mutat Res273:203-12 1992 |
| PubMed ID: 1372103 |
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| Zhukovskaya N, Rydberg B, Karran P, Inactive O6-methylguanine-DNA methyltransferase in human cells. Nucleic Acids Res20:6081-90 1992 |
| PubMed ID: 1461738 |
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| Robins P, Jones CJ, Biggerstaff M, Lindahl T, Wood RD, Complementation of DNA repair in xeroderma pigmentosum group A cell extracts by a protein with affinity for damaged DNA. EMBO J10:3913-21 1991 |
| PubMed ID: 1935910 |
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| Hansson J, Grossman L, Lindahl T, Wood RD, Complementation of the xeroderma pigmentosum DNA repair synthesis defect with Escherichia coli UvrABC proteins in a cell-free system. Nucleic Acids Res18:35-40 1990 |
| PubMed ID: 2408009 |
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| Parrish DD, Lambert MW, Chromatin-associated DNA endonucleases from xeroderma pigmentosum cells are defective in interaction with damaged nucleosomal DNA. Mutat Res235:65-80 1990 |
| PubMed ID: 2308593 |
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| Rydberg B, Spurr N, Karran P, cDNA cloning and chromosomal assignment of the human O6-methylguanine- DNA methyltransferase. cDNA expression in Escherichia coli and gene expression in human cells. J Biol Chem265:9563-9 1990 |
| PubMed ID: 2188979 |
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| Tsongalis GJ, Lambert WC, Lambert MW, Electroporation of normal human DNA endonucleases into xeroderma pigmentosum cells corrects their DNA repair defect. Carcinogenesis11:499-503 1990 |
| PubMed ID: 2311196 |
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| Tsongalis GJ, Lambert WC, Lambert MW, Correction of the ultraviolet light induced DNA-repair defect in xeroderma pigmentosum cells by electroporation of a normal human endonuclease [published erratum appears in Mutat Res 1990 Oct;245(2):135] Mutat Res244:257-63 1990 |
| PubMed ID: 2366820 |
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| Sano H, Shiomi N, Imanishi K, Maie O, Shiomi T, DNA methylation in xeroderma pigmentosum. Mutat Res217:141-51 1989 |
| PubMed ID: 2918867 |
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| Covey JM, D'Incalci M, Tilchen EJ, Zaharko DS, Kohn KW, Differences in DNA damage produced by incorporation of 5-aza-2'- deoxycytidine or 5,6-dihydro-5-azacytidine into DNA of mammalian cells. Cancer Res46:5511-7 1986 |
| PubMed ID: 2428479 |
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| Otsuka F, Kukita A, Ultraviolet hypersensitivity of Cockayne syndrome lymphoblastoid lines-- the effects of exogenous beta-nicotinamide adenine dinucleotide. Photochem Photobiol44:757-60 1986 |
| PubMed ID: 3562572 |
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| Protic-Sabljic M, Whyte DB, Kraemer KH, Hypersensitivity of xeroderma pigmentosum cells to dietary carcinogens. Mutat Res145:89-94 1985 |
| PubMed ID: 3974607 |
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| Lambert WC, Lambert MW, Increased sensitivity of a xeroderma pigmentosum lymphoblastoid cell line to serum deprivation in vitro. In Vitro19:621-4 1983 |
| PubMed ID: 6885101 |
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| Protic-Sabljic, Transfection of Xeroderma pigmentosum cells with cloned DNA (from Cellular Responses To DNA Damage, Alan R. Liss, Inc .) "Cellular Respon To DNA Damage"1983,pp647:621-4 1983 |
| PubMed ID: 6885101 |
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| Lee DE, Okorodudu AO, Lambert WC, Lambert MW, Defective DNA endonuclease activity on anthramycin treated DNA in xeroderma pigmentosum and mouse melanoma cells. Biochem Biophys Res Commun107:395-402 1982 |
| PubMed ID: 6215036 |
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| Okorodudu AO, Lambert WC, Lambert MW, Nuclear deoxyribonuclease activities in normal and xeroderma pigmentosum lymphoblastoid cells. Biochem Biophys Res Commun108:576-84 1982 |
| PubMed ID: 6216888 |
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| Moshell AN, Tarone RE, Newfield SA, Andrews AD, Robbins JH, A simple and rapid method for evaluating the survival of xeroderma pigmentosum lymphoid lines after irradiation with ultraviolet light. In Vitro17:299-307 1981 |
| PubMed ID: 6263790 |
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| Okorodudu, Differences in nuclear deoxyribonuclease activities in normal and xeroderma pigmentosum lymphoblasts. J Cell Biol91:63a (1981):299-307 1981 |
| PubMed ID: 6263790 |
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| Moshell AN, Tarone RE, Barrett SF, Robbins JH, Radiosensitivity in Huntington's disease: implications for pathogenesis and presymptomatic diagnosis. Lancet1:9-11 1980 |
| PubMed ID: 6101401 |
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| Takebe H, Miki Y, Kozuka T, Furuyama JI, Tanaka K, DNA repair characteristics and skin cancers of xeroderma pigmentosum patients in Japan. Cancer Res37:490-5 1977 |
| PubMed ID: 832273 |
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