GM02249

GM02249 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:

16 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

XP8BE; 46,XY; 10-20% of normal UV induced unscheduled DNA synthesis in fibroblasts; similarly affected twin; see GM00671 (fibroblast); no neurological abnormalities; the donor subject carries two mutations in the XPC gene: one results in the insertion of a valine residue after valine at codon 580, while the other is a point mutation that created a nonconservative amino acid change near the carboxyl terminus of the protein. The cell line is either homozygous or hemizygous for these mutations.

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 61%. 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.

GENE MAPPING & DOSAGE STUDIES - Y CHROMOSOME

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

Gene

XPC

Chromosomal Location

3p25

Allelic Variant 1

613208.0003; XERODERMA PIGMENTOSUM, COMPLEMENTATION GROUP C

Identified Mutation

3-BP INS, GGT, CODON 580 AND LYS822GLN; In cell line XP8BE-L1, Li et al. [Nature Genet. 5: 413-417, (1993)] identified 2 mutations: one resulted in the insertion of a valine residue after valine at codon 580, while the other was a point mutation that created a nonconservative amino acid change near the carboxyl terminus of the protein. It could not be determined whether only one or both of these mutations was responsible for the observed repair deficiency. The cell line was either homozygous or hemizygous for these mutations.

Phenotypic Data

Remarks

Publications

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

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

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

Hansson J, Keyse SM, Lindahl T, Wood RD, DNA excision repair in cell extracts from human cell lines exhibiting hypersensitivity to DNA-damaging agents. Cancer Res51:3384-90 1991

PubMed ID: 2054778

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

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

Hirschhorn R, Tzall S, Ellenbogen A, Hot spot mutations in adenosine deaminase deficiency. Proc Natl Acad Sci U S A87:6171-5 1990

PubMed ID: 2166947

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

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

Cleaver JE, Excision repair in xeroderma pigmentosum group C cells is regulated differently in transformed cells and primary fibroblasts. Biochem Biophys Res Commun156:557-62 1988

PubMed ID: 2845984

Cleaver JE, DNA repair in human xeroderma pigmentosum group C cells involves a different distribution of damaged sites in confluent and growing cells. Nucleic Acids Res14:8155-65 1986

PubMed ID: 3774554

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

Chan GL, Little JB, Resistance of plateau-phase human normal and xeroderma pigmentosum fibroblasts to the cytotoxic effect of ultraviolet light. Mutat Res63:401-12 1979

PubMed ID: 522880

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