GM02246

GM02246 LCL from B-Lymphocyte

Description:

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

Affected:

Yes

Sex:

Female

Age:

30 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

XP1BE; 46,XX; 10-20% of normal UV induced unscheduled DNA synthesis in fibroblasts; see GM10881 (fibroblast); skin manifestations but no neurological abnormalities; developed freckles by age 2; 1st tumor at age 4; by age 28, over 100 neoplasma, including malignant melanomas, developed; corneal edema; the donor subject carries a deletion of the dinucleotide AA at positions 1132 and 1133 in the cDNA of the XPC gene, resulting in premature termination of the protein by a new stop codon 15 nucleotides downstream. The deletion may be either homozygous or hemizygous.

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 XP cells. 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 culture was 55%.

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

613208.0004; XERODERMA PIGMENTOSUM, COMPLEMENTATION GROUP C

Identified Mutation

2-BP DEL, 1132AA; In cell line XP1BE-L1, Li et al. [Nature Genet. 5: 413-417, (1993)] found deletion of the dinucleotide AA at positions 1132 and 1133 in the cDNA of the XPC gene. This was predicted to result in premature termination of the protein by a new stop codon 15 nucleotides downstream. The deletion appeared to be either homozygous or hemizygous.

Phenotypic Data

Remarks

Publications

Matta J, Ortiz-Sánchez C, Encarnación-Medina J, Torres-Caraballo S, Oliveras J, Park J, Arroyo MM, Ruiz-Deya G, DNA Repair Capacity and Clinicopathological Characteristics in Puerto Rican Hispanic/Latino Patients with Metastatic Castration-Resistant Prostate Cancer Cancers17: 2024

PubMed ID: 39858060

Mendez P, Taron M, Moran T, Fernandez MA, Requena G, Rosell R, A modified host-cell reactivation assay to quantify DNA repair capacity in cryopreserved peripheral lymphocytes DNA repair10:603-10 2010

PubMed ID: 21546323

Kapetanaki MG, Guerrero-Santoro J, Bisi DC, Hsieh CL, Rapic-Otrin V, Levine AS, The DDB1-CUL4ADDB2 ubiquitin ligase is deficient in xeroderma pigmentosum group E and targets histone H2A at UV-damaged DNA sites Proceedings of the National Academy of Sciences of the United States of America103:2588-93 2006

PubMed ID: 16473935

Khan SG, Oh KS, Shahlavi T, Ueda T, Busch DB, Inui H, Emmert S, Imoto K, Muniz-Medina V, Baker CC, Digiovanna JJ, Schmidt D, Khadavi A, Metin A, Gozukara E, Slor H, Sarasin A, Kraemer KH, Reduced XPC DNA repair gene mRNA levels in clinically normal arents of xeroderma pigmentosum patients. Carcinogenesis27(1):84-94 2005

PubMed ID: 16081512

Hu JJ, Hall MC, Grossman L, Hedayati M, McCullough DL, Lohman K, Case LD, Deficient nucleotide excision repair capacity enhances human prostate cancer risk. Cancer Res64(3):1197-201 2004

PubMed ID: 14871857

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, 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

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

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

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

PubMed ID: 8879589

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

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

Shivji MK, Eker AP, Wood RD, DNA repair defect in xeroderma pigmentosum group C and complementing factor from HeLa cells. J Biol Chem269:22749-57 1994

PubMed ID: 8077226

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

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

Tanaka K, Miura N, Satokata I, Miyamoto I, Yoshida MC, Satoh Y, Kondo S, Yasui A, Okayama H, Okada Y, Analysis of a human DNA excision repair gene involved in group A xeroderma pigmentosum and containing a zinc-finger domain [see comments] Nature348:73-6 1990

PubMed ID: 2234061

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

Protic-Sabljic M, Whyte DB, Kraemer KH, Hypersensitivity of xeroderma pigmentosum cells to dietary carcinogens. Mutat Res145:89-94 1985

PubMed ID: 3974607

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

Harris AL, Karran P, Lindahl T, O6-Methylguanine-DNA methyltransferase of human lymphoid cells: structural and kinetic properties and absence in repair-deficient cells. Cancer Res43:3247-52 1983

PubMed ID: 6342762

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

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