GM05509

GM05509 Fibroblast

Description:

XERODERMA PIGMENTOSUM, COMPLEMENTATION GROUP A; XPA
XPA, DNA DAMAGE RECOGNITION AND REPAIR FACTOR; XPA

Affected:

Yes

Sex:

Female

Age:

17 YR (At Sampling)

Overview

Repository

NIGMS Human Genetic Cell Repository

Subcollection

Heritable Diseases

Class

Disorders of Nucleotide and Nucleic Acid Metabolism

Class

Repair Defective and Chromosomal Instability Syndromes

Cell Type

Fibroblast

Transformant

Untransformed

Race

White

Family Member

Relation to Proband

proband

Confirmation

Clinical summary/Case history

Species

Homo sapiens

Common Name

Human

Remarks

Multiple skin cancers; acute sun sensitivity; nervous system involvement with progressive neurological degeneration; the donor subject is a compound heterozygote for two mutations in the XPA gene: one allele carries a G-to-C substitution at nucleotide 555 (555G>C) in exon 4 with results in a missplice; the second allele carries a G-to-T transversion in intron 3 which abolishes the canonical 3-prime splice site and results in a missplice; XP12BE; < 2% of normal UV induced unscheduled DNA synthesis; see GM02250 (lymphoblast) and GM04429 (SV40 transformed fibroblast).

Characterizations

PDL at Freeze

7.36

Passage Frozen

IDENTIFICATION OF SPECIES OF ORIGIN

Species of Origin Confirmed by Nucleoside Phosphorylase, Glucose-6-Phosphate Dehydrogenase, and Lactate Dehydrogenase Isoenzyme Electrophoresis

Gene

XPA

Chromosomal Location

9q22.3-q31

Allelic Variant 1

missplice; XERODERMA PIGMENTOSUM, COMPLEMENTATION GROUP A

Identified Mutation

555G>C

Gene

XPA

Chromosomal Location

9q22.3-q31

Allelic Variant 2

missplice; XERODERMA PIGMENTOSUM, COMPLEMENTATION GROUP A

Identified Mutation

G>T transversion in intron 3

Phenotypic Data

Remarks

Publications

Wang QE, Han C, Zhao R, Wani G, Zhu Q, Gong L, Battu A, Racoma I, Sharma N, Wani AA, p38 MAPK- and Akt-mediated p300 phosphorylation regulates its degradation to facilitate nucleotide excision repair Nucleic acids research41:1722-33 2012

PubMed ID: 23275565

Meeran SM, Mantena SK, Elmets CA, Katiyar SK, (-)-Epigallocatechin-3-gallate prevents photocarcinogenesis in mice through interleukin-12-dependent DNA repair Cancer research66:5512-20 2006

PubMed ID: 16707481

Meeran SM, Mantena SK, Katiyar SK, Prevention of ultraviolet radiation-induced immunosuppression by (-)-epigallocatechin-3-gallate in mice is mediated through interleukin 12-dependent DNA repair Clinical cancer research : an official journal of the American Association for Cancer Research12:2272-80 2006

PubMed ID: 16609044

Wang QE, Zhu Q, Wani G, El-Mahdy MA, Li J, Wani AA, DNA repair factor XPC is modified by SUMO-1 and ubiquitin following UV irradiation Nucleic acids research33:4023-34 2005

PubMed ID: 16030353

Ridley AJ, Colley J, Wynford-Thomas D, Jones CJ, Characterisation of novel mutations in Cockayne syndrome type A and xeroderma pigmentosum group C subjects Journal of human genetics50:151-4 2004

PubMed ID: 15744458

Rapic-Otrin V, McLenigan MP, Bisi DC, Gonzalez M, Levine AS, Sequential binding of UV DNA damage binding factor and degradation of the p48 subunit as early events after UV irradiation. Nucleic Acids Res30(11):2588-98 2002

PubMed ID: 12034848

Katsumi S, Kobayashi N, Imoto K, Nakagawa A, Yamashina Y, Muramatsu T, Shirai T, Miyagawa S, Sugiura S, Hanaoka F, Matsunaga T, Nikaido O, Mori T, In situ visualization of ultraviolet-light-induced DNA damage repair in locally irradiated human fibroblasts. J Invest Dermatol117(5):1156-61 2001

PubMed ID: 11710927

Dittmann KH, Dikomey E, Mayer C, Rodemann HP, The Bowman-Birk protease inhibitor enhances clonogenic cell survival of ionizing radiation-treated nucleotide excision repair-competent cells but not of xeroderma pigmentosum cells. Int J Radiat Biol76(2):223-9 2000

PubMed ID: 10716643

Thielmann HW, Popanda O, Staab HJ, Subnuclear distribution of DNA topoisomerase I and Bax protein in normal and xeroderma pigmentosum fibroblasts after irradiation with UV light and gamma rays or treatment with topotecan. J Cancer Res Clin Oncol125:193-208 1999

PubMed ID: 10235474

Ali RB, Teo AK, Oh HK, Chuang LS, Ayi TC, Li BF, Implication of localization of human DNA repair enzyme O6-methylguanine-DNA methyltransferase at active transcription sites in transcription-repair coupling of the mutagenic O6-methylguanine lesion. Mol Cell Biol18:1660-9 1998

PubMed ID: 9488483

States JC, McDuffie ER, Myrand SP, McDowell M, Cleaver JE, Distribution of mutations in the human xeroderma pigmentosum group A gene and their relationships to the functional regions of the DNA damage recognition protein. Hum Mutat12:103-13 1998

PubMed ID: 9671271

Thielmann HW, Popanda O, Irradiation with ultraviolet light and -rays increases the level of DNA topoisomerase II in nuclei of normal and xeroderma pigmentosum fibroblasts. Int J Oncol12(2):265-71 1998

PubMed ID: 9458348

Thielmann HW, Popanda O, Doxorubicin and gamma rays increase the level of DNA topoisomerase IIalpha in nuclei of normal and xeroderma pigmentosum fibroblasts. J Cancer Res Clin Oncol124:355-66 1998

PubMed ID: 9719498

Cheng L, Bucana CD, Wei Q, Fluorescence in situ hybridization method for measuring transfection efficiency. Biotechniques21(3):486-91 1996

PubMed ID: 8879589

Davis K, Tomkins DJ, Rainbow AJ, Roberts syndrome fibroblasts showing cisplatin hypersensitivity have normal host cell reactivation of cisplatin-treated adenovirus and normal capacity of cisplatin-treated cells for adenovirus DNA synthesis. Somat Cell Mol Genet22:393-402 1996

PubMed ID: 9039848

Moriwaki S, Stefanini M, Lehmann AR, Hoeijmakers JH, Robbins JH, Rapin I, Botta E, Tanganelli B, Vermeulen W, Broughton BC, Kraemer KH, DNA repair and ultraviolet mutagenesis in cells from a new patient with xeroderma pigmentosum group G and cockayne syndrome resemble xeroderma pigmentosum cells. J Invest Dermatol107(4):647-53 1996

PubMed ID: 8823375

Parshad RP, Sanford KK, Price FM, Melnick LK, Nee LE, Schapiro MB, Tarone RE, Robbins JH, Fluorescent light-induced chromatid breaks distinguish Alzheimer disease cells from normal cells in tissue culture. Proc Natl Acad Sci U S A93:5146-50 1996

PubMed ID: 8643543

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

Matsuda T, Saijo M, Kuraoka I, Kobayashi T, Nakatsu Y, Nagai A, Enjoji T, Masutani C, Sugasawa K, Hanaoka F, et al, DNA repair protein XPA binds replication protein A (RPA). J Biol Chem270:4152-7 1995

PubMed ID: 7876167

Satokata I, Uchiyama M, Tanaka K, Two novel splicing mutations in the XPA gene in patients with group A xeroderma pigmentosum. Hum Mol Genet4:1993-4 1995

PubMed ID: 8595429

Jones CJ, Lloyd RS, Wood RD, Analysis of cells harboring a putative DNA repair gene reveals a lack of evidence for a second independent xeroderma pigmentosum group A correcting gene. Mutat Res324(4):159-64 1994

PubMed ID: 7519740

Dypbukt JM, Atzori L, Edman CC, Grafstrom RC, Thiol status and cytopathological effects of acrolein in normal and xeroderma pigmentosum skin fibroblasts. Carcinogenesis14(5):975-80 1993

PubMed ID: 8504492

Leadon SA, Cooper PK, Preferential repair of ionizing radiation-induced damage in the transcribed strand of an active human gene is defective in Cockayne syndrome. Proc Natl Acad Sci U S A90(22):10499-503 1993

PubMed ID: 8248136

Lu X, Lane DP, Differential induction of transcriptionally active p53 following UV or ionizing radiation: defects in chromosome instability syndromes? Cell75:765-78 1993

PubMed ID: 8242748

Chen RH, Maher VM, McCormick JJ, Lack of a cell cycle-dependent strand bias for mutations induced in the HPRT gene by (+/-)-7 beta,8 alpha-dihydroxy-9 alpha,10 alpha-epoxy-7,8,9,10-tetrahydrobenzo(a)pyrene in excision repair-deficient human cells. Cancer Res51(10):2587-92 1991

PubMed ID: 1902394

Colicos MA, Haj-Ahmad Y, Valerie K, Henderson EE, Rainbow AJ, Construction of a recombinant adenovirus containing the denV gene from bacteriophage T4 which can partially restore the DNA repair deficiency in xeroderma pigmentosum fibroblasts. Carcinogenesis12:249-55 1991

PubMed ID: 1704821

Kochevar IE, Walsh AA, Green HA, Sherwood M, Shih AG, Sutherland BM, DNA damage induced by 193-nm radiation in mammalian cells. Cancer Res51:288-93 1991

PubMed ID: 1988091

McGregor WG, Chen RH, Lukash L, Maher VM, McCormick JJ, Cell cycle-dependent strand bias for UV-induced mutations in the transcribed strand of excision repair-proficient human fibroblasts but not in repair-deficient cells. Mol Cell Biol11(4):1927-34 1991

PubMed ID: 2005888

Mirzayans R, Paterson MC, Differential repair of 1-beta-D-arabinofuranosylcytosine-detectable sites in DNA of human fibroblasts exposed to ultraviolet light and 4-nitroquinoline 1-oxide. Mutat Res255(1):57-65 1991

PubMed ID: 1906130

Mirzayans R, Paterson MC, Dose-dependent increase in repair of 1-beta-D-arabinofuranosylcytosine-detectable DNA lesions in UV-treated xeroderma pigmentosum (group A) fibroblasts. Mutat Res262(3):151-7 1991

PubMed ID: 2002813

Seetharam S, Kraemer KH, Waters HL, Seidman MM, Ultraviolet mutational spectrum in a shuttle vector propagated in xeroderma pigmentosum lymphoblastoid cells and fibroblasts. Mutat Res254:97-105 1991

PubMed ID: 1986277

Wilson VL, Foiles PG, Chung FL, Povey AC, Frank AA, Harris CC, Detection of acrolein and crotonaldehyde DNA adducts in cultured human cells and canine peripheral blood lymphocytes by 32P-postlabeling and nucleotide chromatography. Carcinogenesis12:1483-90 1991

PubMed ID: 1860170

Cheng RZ, Murano S, Kurz B, Shmookler Reis RJ, Homologous recombination is elevated in some Werner-like syndromes but not during normal in vitro or in vivo senescence of mammalian cells. Mutat Res237:259-69 1990

PubMed ID: 2079965

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

Seetharam S, Kraemer KH, Waters HL, Seidman MM, Mutational hotspot variability in an ultraviolet-treated shuttle vector plasmid propagated in xeroderma pigmentosum and normal human lymphoblasts and fibroblasts. J Mol Biol212(3):433-6 1990

PubMed ID: 2182882

Mirzayans R, Liuzzi M, Paterson MC, Methylmethanesulfonate-induced DNA damage and its repair in cultured human fibroblasts: normal rates of induction and removal of alkali-labile sites in xeroderma pigmentosum (group A) cells. Carcinogenesis9(12):2257-63 1988

PubMed ID: 3191570

Kantor GJ, Player AN, A further definition of characteristics of DNA-excision repair in xeroderma pigmentosum complementation group A strains. Mutat Res166(1):79-88 1986

PubMed ID: 3724780

Van Houten B, Masker WE, Carrier WL, Regan JD, Quantitation of carcinogen-induced DNA damage and repair in human cells with the UVR ABC excision nuclease from Escherichia coli. Carcinogenesis7(1):83-7 1986

PubMed ID: 3080255

Mirzayans R, Paterson MC, Waters R, Defective repair of a class of 4NQO-induced alkali-labile DNA lesions in xeroderma pigmentosum complementation group A fibroblasts. Carcinogenesis6:555-9 1985

PubMed ID: 3921271

Domoradzki J, Pegg AE, Dolan ME, Maher VM, McCormick JJ, Correlation between O6-methylguanine-DNA-methyltransferase activity and resistance of human cells to the cytotoxic and mutagenic effect of N- methyl-N'-nitro-N-nitrosoguanidine. Carcinogenesis5:1641-7 1984

PubMed ID: 6499116

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

Kantor GJ, Hull DR, The rate of removal of pyrimidine dimers in quiescent cultures of normal human and xeroderma pigmentosum cells. Mutat Res132(1-2):21-31 1984

PubMed ID: 6472315

Mahoney EM, Ball JC, Swenson DH, Richmond D, Maher VM, McCormick JJ, Cytotoxicity and mutagenicity of aflatoxin dichloride in normal and repair deficient diploid human fibroblasts. Chem Biol Interact50(1):59-76 1984

PubMed ID: 6428759

Fornace AJ, Seres DS, Detection of DNA single-strand breaks during the repair of UV damage in xeroderma pigmentosum cells. Radiat Res93(1):107-11 1983

PubMed ID: 6823503

Hull DR, Kantor GJ, Evidence that DNA excision-repair in xeroderma pigmentosum group A is limited but biologically significant. Mutat Res112(3):169-79 1983

PubMed ID: 6306455

Robbins JH, Polinsky RJ, Moshell AN, Evidence that lack of deoxyribonucleic acid repair causes death of neurons in xeroderma pigmentosum. Ann Neurol13:682-4 1983

PubMed ID: 6881931

Konze-Thomas B, Hazard RM, Maher VM, McCormick JJ, Extent of excision repair before DNA synthesis determines the mutagenic but not the lethal effect of UV radiation. Mutat Res94(2):421-34 1982

PubMed ID: 7110182

Yang LL, Maher VM, McCormick JJ, Relationship between excision repair and the cytotoxic and mutagenic effect of the 'anti' 7,8-diol-9,10-epoxide of benzo[a]pyrene in human cells. Mutat Res94(2):435-47 1982

PubMed ID: 6810167

Kantor GJ, Setlow RB, Rate and extent of DNA repair in nondividing human diploid fibroblasts. Cancer Res41(3):819-25 1981

PubMed ID: 7459869

Nishiyama Y, Rapp F, Enhanced capacity of DNA repair in human cytomegalovirus-infected cells. J Virol38(1):164-72 1981

PubMed ID: 6264099

Simon L, Hazard RM, Maher VM, McCormick JJ, Enhanced cell killing and mutagenesis by ethylnitrosourea in xeroderma pigmentosum cells. Carcinogenesis2:567-70 1981

PubMed ID: 7273335

Aust AE, Falahee KJ, Maher VM, McCormick JJ, Human cell-mediated benzo(a)pyrene cytotoxicity and mutagenicity in human diploid fibroblasts. Cancer Res40(11):4070-5 1980

PubMed ID: 6258771

Heflich RH, Hazard RM, Lommel L, Scribner JD, Maher VM, McCormick JJ, A comparison of the DNA binding, cytotoxicity and repair synthesis induced in human fibroblasts by reactive derivatives of aromatic amide carcinogens. Chem Biol Interact29(1):43-56 1980

PubMed ID: 7356535

Kaye J, Smith CA, Hanawalt PC, DNA repair in human cells containing photoadducts of 8-methoxypsoralen or angelicin. Cancer Res40(3):696-702 1980

PubMed ID: 7471088

Yang LL, Maher VM, McCormick JJ, Error-free excision of the cytotoxic,mutagenic N2-deoxyguanosine DNA adduct formed in human fibroblasts by (+/-)-7 beta, 8 alpha-dihydroxy-9 alpha, 10 alpha-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene. Proc Natl Acad Sci U S A77(10):5933-7 1980

PubMed ID: 6934524

Coppey J, Nocentini S, Survival and herpes virus production of normal and xeroderma pigmentosum fibroblasts after treatment with formaldehyde. Mutat Res62(2):355-61 1979

PubMed ID: 228186

Kantor GJ, Hull DR, An effect of ultraviolet light on RNA and protein synthesis in nondividing human diploid fibroblasts. Biophys J27(3):359-70 1979

PubMed ID: 95567

Maher VM, Dorney DJ, Mendrala AL, Konze-Thomas B, McCormick JJ, DNA excision-repair processes in human cells can eliminate the cytotoxic and mutagenic consequences of ultraviolet irradiation. Mutat Res62(2):311-23 1979

PubMed ID: 503098

McCaw BA, Dipple A, Young S, Roberts JJ, Excision of hydrocarbon-DNA adducts and consequent cell survival in normal and repair defective human cells. Chem Biol Interact22(2-3):139-51 1978

PubMed ID: 699169

Sutherland BM, Oliver R, Culture conditions affect photoreactivating enzyme levels in human fibroblasts. Biochim Biophys Acta442(3):358-67 1976

PubMed ID: 963054

Sutherland BM, Oliver R, Fuselier CO, Sutherland JC, Photoreactivation of pyrimidine dimers in the DNA of normal and xeroderma pigmentosum cells. Biochemistry15(2):402-6 1976

PubMed ID: 1247526

Kraemer KH, Coon HG, Petinga RA, Barrett SF, Rahe AE, Robbins JH, Genetic heterogeneity in xeroderma pigmentosum: complementation groups and their relationship to DNA repair rates. Proc Natl Acad Sci U S A72:59-63 1975

PubMed ID: 164028

Maher VM, Birch N, Otto JR, MacCormick JJ, Cytotoxicity of carcinogenic aromatic amides in normal and xeroderma pigmentosum fibroblasts with different DNA repair capabilities. J Natl Cancer Inst54(6):1287-94 1975

PubMed ID: 1133846

Robbins JH, Kraemer KH, Lutzner MA, Festoff BW, Coon HG, Xeroderma pigmentosum. An inherited diseases with sun sensitivity, multiple cutaneous neoplasms, and abnormal DNA repair. Ann Intern Med80:221-48 1974

PubMed ID: 4811796