GM04312
Fibroblast from Skin, Unspecified
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 |
Repair Defective and Chromosomal Instability Syndromes |
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Biopsy Source
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Unspecified
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Cell Type
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Fibroblast
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Tissue Type
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Skin
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Transformant
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Simian Virus 40
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Sample Source
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Fibroblast from Skin, Unspecified
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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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| 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 |
Severely affected; mental retardation; gait disturbance; increased chromosome breakage; < 2% of normal UV induced unscheduled DNA synthesis; T-antigen positive; 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; XP20S; SV40 transformed; see GM02345 lymphoblast. |
| Rieckher M, Gallrein C, Alquezar-Artieda N, Bourached-Silva N, Vaddavalli PL, Mares D, Backhaus M, Blindauer T, Greger K, Wiesner E, Pontel LB, Schumacher B, Distinct DNA repair mechanisms prevent formaldehyde toxicity during development, reproduction and aging Nucleic acids research: 2024 |
| PubMed ID: 38894680 |
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| Sarmini L, Meabed M, Emmanouil E, Atsaves G, Robeska E, Karwowski BT, Campalans A, Gimisis T, Khobta A, Requirement of transcription-coupled nucleotide excision repair for the removal of a specific type of oxidatively induced DNA damage Nucleic acids research: 2023 |
| PubMed ID: 37026475 |
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| Kitsera N, Rodriguez-Alvarez M, Emmert S, Carell T, Khobta A, Nucleotide excision repair of abasic DNA lesions Nucleic acids research: 2019 |
| PubMed ID: 31226203 |
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| Kong YW, Dreaden EC, Morandell S, Zhou W, Dhara SS, Sriram G, Lam FC, Patterson JC, Quadir M, Dinh A, Shopsowitz KE, Varmeh S, Yilmaz ÖH, Lippard SJ, Reinhardt HC, Hemann MT, Hammond PT, Yaffe MB, Enhancing chemotherapy response through augmented synthetic lethality by co-targeting nucleotide excision repair and cell-cycle checkpoints Nature communications11:4124 2018 |
| PubMed ID: 32807787 |
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| Kitsera N, Gasteiger K, Lühnsdorf B, Allgayer J, Epe B, Carell T, Khobta A, Cockayne syndrome: varied requirement of transcription-coupled nucleotide excision repair for the removal of three structurally different adducts from transcribed DNA PloS one9:e94405 2014 |
| PubMed ID: 24713864 |
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| Enoiu M, Jiricny J, Schärer OD, Repair of cisplatin-induced DNA interstrand crosslinks by a replication-independent pathway involving transcription-coupled repair and translesion synthesis Nucleic acids research40:8953-64 2012 |
| PubMed ID: 22810206 |
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| Jowsey PA, Williams FM, Blain PG, DNA damage responses in cells exposed to sulphur mustard Toxicology letters209:1-10 2011 |
| PubMed ID: 22119920 |
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| Pathania S, Nguyen J, Hill SJ, Scully R, Adelmant GO, Marto JA, Feunteun J, Livingston DM, BRCA1 Is Required for Postreplication Repair after UV-Induced DNA Damage Molecular cell44:235-51 2010 |
| PubMed ID: 21963239 |
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| 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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| Yoder K, Sarasin A, Kraemer K, McIlhatton M, Bushman F, Fishel R, The DNA repair genes XPB and XPD defend cells from retroviral infection Proceedings of the National Academy of Sciences of the United States of America103:4622-7 2006 |
| PubMed ID: 16537383 |
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| Albertella MR, Green CM, Lehmann AR, O'Connor MJ, A role for polymerase eta in the cellular tolerance to cisplatin-induced damage Cancer research65:9799-806 2005 |
| PubMed ID: 16267001 |
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| Camenisch U, Dip R, Schumacher SB, Schuler B, Naegeli H, Recognition of helical kinks by xeroderma pigmentosum group A protein triggers DNA excision repair Nature structural & molecular biology13:278-84 2005 |
| PubMed ID: 16491090 |
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| Krzesniak M, Butkiewicz D, Samojedny A, Chorazy M, Rusin M, Polymorphisms in TDG and MGMT genes - epidemiological and functional study in lung cancer patients from Poland Annals of human genetics68:300-12 2004 |
| PubMed ID: 15225156 |
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| Muheim-Lenz R, Buterin T, Marra G, Naegeli H, Short-patch correction of C/C mismatches in human cells Nucleic acids research32:6696-705 2004 |
| PubMed ID: 15613598 |
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| Reynolds M, Peterson E, Quievryn G, Zhitkovich A, Human Nucleotide Excision Repair Efficiently Removes Chromium-DNA Phosphate Adducts and Protects Cells against Chromate Toxicity. J Biol Chem279(29):30419-24 2004 |
| PubMed ID: 15087443 |
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| Muheim R, Buterin T, Colgate KC, Kolbanovsij A, Geacintov NE, Naegeli H, Modulation of human nucleotide excision repair by 5-methylcytosines. Biochemistry42(11):3247-54 2003 |
| PubMed ID: 12641456 |
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| Morelli C, Karayianni E, Magnanini C, Mungall AJ, Thorland E, Negrini M, Smith DI, Barbanti-Brodano G, Cloning and characterization of the common fragile site FRA6F harboring a replicative senescence gene and frequently deleted in human tumors Oncogene21:7266-76 2002 |
| PubMed ID: 12370818 |
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| Hirano J, Wang X, Kita K, Higuchi Y, Nakanishi H, Uzawa K, Yokoe H, Tanzawa
H, Yamaura A, Yamamori H, Nakajima N, Nishikiori C, Suzuki N, Low levels of NPM gene expression in UV-sensitive human cell lines. Cancer Lett153(1-2):183-8 2000 |
| PubMed ID: 10779648 |
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| Quievryn G, Zhitkovich A, Loss of DNA-protein crosslinks from formaldehyde-exposed cells occurs through
spontaneous hydrolysis and an active repair process linked to proteosome
function. Carcinogenesis21(8):1573-80 2000 |
| PubMed ID: 10910961 |
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| Prince PR, Ogburn CE, Moser MJ, Emond MJ, Martin GM, Monnat RJ Jr, Cell fusion corrects the 4-nitroquinoline 1-oxide sensitivity of Werner syndrome fibroblast cell lines. Hum Genet105:132-8 1999 |
| PubMed ID: 10480367 |
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| States JC, Myrand SP, Splice site mutations in a xeroderma pigmentosum group A patient with delayed onset of neurological disease. Mutat Res363:171-7 1996 |
| PubMed ID: 8765158 |
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| Yoon YS, Kim JW, Kang KW, Kim YS, Choi KH, Joe CO, Poly(ADP-ribosyl)ation of histone H1 correlates with internucleosomal DNA fragmentation during apoptosis. J Biol Chem271:9129-34 1996 |
| PubMed ID: 8621564 |
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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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| Luethy JD, Holbrook NJ, Activation of the gadd153 promoter by genotoxic agents: a rapid and specific response to DNA damage. Cancer Res52:5-10 1992 |
| PubMed ID: 1727386 |
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| Saito H, Moses RE, Immortalization of Werner syndrome and progeria fibroblasts Experimental cell research192:373-9 1991 |
| PubMed ID: 1671011 |
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| Sun Y, Moses RE, Reactivation of psoralen-reacted plasmid DNA in Fanconi anemia, xeroderma pigmentosum, and normal human fibroblast cells. Somat Cell Mol Genet17:229-38 1991 |
| PubMed ID: 2047939 |
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| Rinaldy A, Bellew T, Egli E, Lloyd RS, Increased UV resistance in xeroderma pigmentosum group A cells after transformation with a human genomic DNA clone. Proc Natl Acad Sci U S A87:6818-22 1990 |
| PubMed ID: 2168562 |
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| Satokata I, Tanaka K, Miura N, Miyamoto I, Satoh Y, Kondo S, Okada Y, Characterization of a splicing mutation in group A xeroderma pigmentosum. Proc Natl Acad Sci U S A87:9908-12 1990 |
| PubMed ID: 1702221 |
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| Wood CM, Moses RE, Ethyl methane sulfonate- and bleomycin-generated deletion mutations at HPRT locus in xeroderma pigmentosum complementation group D fibroblasts. Somat Cell Mol Genet15:345-57 1989 |
| PubMed ID: 2474861 |
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| Wood CM, Timme TL, Hurt MM, Brinkley BR, Ledbetter DH, Moses RE, Transformation of DNA repair-deficient human diploid fibroblasts with a simian virus 40 plasmid. Exp Cell Res169:543-53 1987 |
| PubMed ID: 3030788 |
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| Barbis DP, Schultz RA, Friedberg EC, Isolation and partial characterization of virus-transformed cell lines representing the A, G and variant complementation groups of xeroderma pigmentosum. Mutat Res165:175-84 1986 |
| PubMed ID: 3010096 |
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| Protic-Sabljic M, Kraemer KH, Host cell reactivation by human cells of DNA expression vectors damaged by ultraviolet radiation or by acid-heat treatment. Carcinogenesis7:1765-70 1986 |
| PubMed ID: 3463438 |
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| Colbere-Garapin F, Horaud F, Kourilsky P, Garapin A, Comparative expression of the hepatitis B surface antigen gene in biochemically transformed human, simian and murine cells. J Gen Virol66 ( Pt 8):1741-52 1985 |
| PubMed ID: 2991437 |
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| Kuhnlein U, Comparison of apurinic DNA-binding protein from an ataxia telangiectasia and a HeLa cell line. Evidence for an altered processing of apurinic/apyrimidinic endonuclease. J Biol Chem260:14918-24 1985 |
| PubMed ID: 2415510 |
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| Protic-Sabljic M, Kraemer KH, One pyrimidine dimer inactivates expression of a transfected gene in xeroderma pigmentosum cells. Proc Natl Acad Sci U S A82:6622-6 1985 |
| PubMed ID: 2995975 |
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| Protic-Sabljic M, Whyte D, Fagan J, Howard BH, Gorman CM, Padmanabhan R, Kraemer KH, Quantification of expression of linked cloned genes in a simian virus 40-transformed xeroderma pigmentosum cell line. Mol Cell Biol5:1685-93 1985 |
| PubMed ID: 2991746 |
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| Schultz RA, Barbis DP, Friedberg EC, Studies on gene transfer and reversion to UV resistance in xeroderma pigmentosum cells. Somat Cell Mol Genet11:617-24 1985 |
| PubMed ID: 3000003 |
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| Gantt R, Taylor WG, Camalier RF, Stephens EV, Repair of DNA-protein cross-links in an excision repair-deficient human cell line and its simian virus 40-transformed derivative. Cancer Res44:1809-12 1984 |
| PubMed ID: 6324989 |
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| Kuhnlein U, Tsang SS, Lokken O, Tong S, Twa D, Cell lines from xeroderma pigmentosum complementation group A lack a single-stranded-DNA-binding activity. Biosci Rep3:667-74 1983 |
| PubMed ID: 6684957 |
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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,pp647:667-74 1983 |
| PubMed ID: 6684957 |
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| Takano T, Noda M, Tamura T, Transfection of cells from a xeroderma pigmentosum patient with normal human DNA confers UV resistance. Nature296:269-70 1982 |
| PubMed ID: 7063029 |
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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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| Takebe H, Nii S, Ishii MI, Utsumi H, Comparative studies of host-cell reactivation, colony forming ability and excision repair after UV irradiation of xeroderma pigmentosum, normal human and some other mammalian cells. Mutat Res25:383-90 1974 |
| PubMed ID: 4373650 |
| Split Ratio |
1:8 |
| Temperature |
37 C |
| Percent CO2 |
5% |
| Percent O2 |
AMBIENT |
| Medium |
Eagle's Minimum Essential Medium with Earle's salts and non-essential amino acids with 2mM L-glutamine or equivalent |
| Serum |
10% fetal bovine serum Not inactivated |
| Substrate |
None specified |
| Supplement |
- |
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