GM00671

GM00671 Fibroblast

Description:

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

Affected:

Yes

Sex:

Male

Age:

15 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

XP8BE; ATCC CRL 1158; 10-20% of normal UV induced unscheduled DNA synthesis; see GM02249 (lymphoblastoid); similarly affected twin and 2 brothers; 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

Passage Frozen

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

Wang G, Chuang L, Zhang X, Colton S, Dombkowski A, Reiners J, Diakiw A, Xu XS, The initiative role of XPC protein in cisplatin DNA damaging treatment-mediated cell cycle regulation. Nucleic Acids Res32(7):2231-40 2004

PubMed ID: 15107491

Rubbi CP, Milner J, Analysis of nucleotide excision repair by detection of single-stranded DNA transients. Carcinogenesis22(11):1789-96 2001

PubMed ID: 11698340

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

Ratner JN, Balasubramanian B, Corden J, Warren SL, Bregman DB, Ultraviolet radiation-induced ubiquitination and proteasomal degradation of the large subunit of RNA polymerase II. Implications for transcription-coupled DNA repair. J Biol Chem273(9):5184-9 1998

PubMed ID: 9478972

Bregman DB, Halaban R, van Gool AJ, Henning KA, Friedberg EC, Warren SL, UV-induced ubiquitination of RNA polymerase II: a novel modification deficient in Cockayne syndrome cells. Proc Natl Acad Sci U S A93:11586-90 1996

PubMed ID: 8876179

Yanagisawa J, Seki M, Ui M, Enomoto T, Alteration of a DNA-dependent ATPase activity in xeroderma pigmentosum complementation group C cells. J Biol Chem267:3585-8 1992

PubMed ID: 1310977

Cleaver JE, DNA repair deficiencies and cellular senescence are unrelated in xeroderma pigmentosum cell lines. Mech Ageing Dev27:189-96 1984

PubMed ID: 6492896

Cleaver JE, Inactivation of ultraviolet repair in normal and xeroderma pigmentosum cells by methyl methanesulfonate. Cancer Res42:860-3 1982

PubMed ID: 7059984

Weichselbaum RR, Nove J, Little JB, Deficient recovery from potentially lethal radiation damage in ataxia telengiectasia and xeroderma pigmentosum. Nature271:261-2 1978

PubMed ID: 622166