GM02248

GM02248 LCL from B-Lymphocyte

Description:

XERODERMA PIGMENTOSUM, COMPLEMENTATION GROUP C; XPC
XPC COMPLEX SUBUNIT, DNA DAMAGE RECOGNITION AND REPAIR FACTOR; XPC

Affected:

Yes

Sex:

Male

Age:

25 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

Biopsy Source

Peripheral vein

Cell Type

B-Lymphocyte

Tissue Type

Blood

Transformant

Epstein-Barr Virus

Sample Source

LCL from B-Lymphocyte

Race

White

Family Member

Relation to Proband

proband

Confirmation

Clinical summary/Case history

Species

Homo sapiens

Common Name

Human

Remarks

XP3BE; 46,XY; 10-20% of normal UV induced unscheduled DNA synthesis in fibroblasts; lymphoblastoid cell culture is hypersensitive to UV induced cell killing and mutagenesis; see GM00030 (fibroblast); no neurological abnormalities; the donor subject carries an 83-bp insertion starting at position 462 in the XPC cDNA.

Characterizations

IDENTIFICATION OF SPECIES OF ORIGIN

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

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 65%. 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 dihydrofollate reductase, a housekeeping gene, was the same as in controls.

GENE MAPPING & DOSAGE STUDIES - Y CHROMOSOME

PCR analysis of DNA from this cell culture gave a positive result with a primer for Yq11, DYS227.

MEX PHENOTYPES

Sklar and Strauss (NATURE 289:417-420,1981) assigned this culture a mex- phenotype based upon its ability to remove O6-MeG from alkylated DNA.

Gene

XPC

Chromosomal Location

3p25

Allelic Variant 1

613208.0002; XERODERMA PIGMENTOSUM, COMPLEMENTATION GROUP C

Identified Mutation

83-BP INS, NT462; In cell line XP3BE-L3, Li et al. [Nature Genet. 5: 413-417, (1993)] demonstrated an 83-bp insertion starting at position 462 in the XPC cDNA.

Phenotypic Data

Remarks

Publications

Wang H, Hoffman PD, Lawrence C, Hays JB, Testing excision models for responses of mismatch-repair systems to UV photoproducts in DNA Environmental and molecular mutagenesis47:296-306 2006

PubMed ID: 16493608

Cleaver JE, Thompson LH, Richardson AS, States JC, A summary of mutations in the UV-sensitive disorders: xeroderma pigmentosum, Cockayne syndrome, and trichothiodystrophy. Hum Mutat14(1):9-22 1999

PubMed ID: 10447254

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

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

Reardon JT, Mu D, Sancar A, Overproduction, purification, and characterization of the XPC subunit of the human DNA repair excision nuclease. J Biol Chem271:19451-6 1996

PubMed ID: 8702634

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

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

Li L, Bales ES, Peterson CA, Legerski RJ, Characterization of molecular defects in xeroderma pigmentosum group C. Nat Genet5(4):413-7 1993

PubMed ID: 8298653

Zhukovskaya N, Rydberg B, Karran P, Inactive O6-methylguanine-DNA methyltransferase in human cells. Nucleic Acids Res20:6081-90 1992

PubMed ID: 1461738

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

Teitz T, Eli D, Penner M, Bakhanashvili M, Naiman T, Timme TL, Wood CM, Moses RE, Canaani D, Expression of the cDNA for the beta subunit of human casein kinase II confers partial UV resistance on xeroderma pigmentosum cells. Mutat Res236:85-97 1990

PubMed ID: 1694965

Sano H, Shiomi N, Imanishi K, Maie O, Shiomi T, DNA methylation in xeroderma pigmentosum. Mutat Res217:141-51 1989

PubMed ID: 2918867

Sequin, Ultraviolet light-induced chromosomal aberrations in cultured cells from Cockayne syndrome & complementation group C xeroderma pigmentosum patients: Lack of correlation with cancer susceptibility. Am J Hum Genet42:468 (1988):141-51 1988

PubMed ID: 2918867

Tatsumi K, Toyoda M, Hashimoto T, Furuyama J, Kurihara T, Inoue M, Takebe H, Differential hypersensitivity of xeroderma pigmentosum lymphoblastoid cell lines to ultraviolet light mutagenesis. Carcinogenesis8:53-7 1987

PubMed ID: 3802395

Berger NA, Sikorski GW, Poly(adenosine diphosphoribose) synthesis in ultraviolet-irradiated xeroderma pigmentosum cells reconstituted with Micrococcus luteus UV endonuclease. Biochemistry20:3610-4 1981

PubMed ID: 6266458

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

Sklar R, Strauss B, Removal of O6-methylguanine from DNA of normal and xeroderma pigmentosum-derived lymphoblastoid lines. Nature289:417-20 1981

PubMed ID: 7464910

Andrews AD, Robbins JH, Kraemer KH, Buell DN, Xeroderma pigmentosum long-term lymphoid lines with increased ultraviolet sensitivity. J Natl Cancer Inst53:691-693 1974

PubMed ID: 4416919

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