GM16088
Fibroblast from Skin, Unspecified
Description:
LIG4 SYNDROME
LIGASE IV, DNA, ATP-DEPENDENT; LIG4
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Repository
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NIGMS Human Genetic Cell Repository
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| Subcollection |
Heritable Diseases |
| Class |
Disorders of Nucleotide and Nucleic Acid Metabolism |
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Biopsy Source
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Unspecified
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Cell Type
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Fibroblast
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Tissue Type
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Skin
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Transformant
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Untransformed
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Sample Source
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Fibroblast from Skin, Unspecified
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Race
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White
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Family Member
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1
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Relation to Proband
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proband
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Confirmation
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Clinical summary/Case history
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Species
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Homo sapiens
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Common Name
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Human
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Remarks
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| IDENTIFICATION OF SPECIES OF ORIGIN |
Species of Origin Confirmed by Nucleoside Phosphorylase,Glucose-6-Phosphate Dehydrogenase, and Lactate Dehydrogenase Isoenzyme Electrophoresis |
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| Gene |
LIG4 |
| Chromosomal Location |
13q22-q34 |
| Allelic Variant 1 |
601837.0004; LIG4 SYNDROME |
| Identified Mutation |
ARG278HIS; O'Driscoll et al. [Molec. Cell 8: 1175-1185 (2001)] identified 3 amino acid substitutions in homozygosity in the LIG4 gene of patient 411BR with LIG4 syndrome (606593): ala3 to val, resulting from a C-to-T transition at nucleotide 8, thr9 to ile, resulting from a C-to-T transition at nucleotide 26, and arg278 to his, resulting from a G-to-A transition at nucleotide 833. The arg278-to-his mutation was identical to that identified in patient 180BR, who had leukemia and whose cell line was radiosensitive and defective in double-strand break repair, by Riballo et al. [Curr. Biol. 9: 699-702 (1999)]. The arg278 residue lies within a highly conserved motif encompassing the active site, and the substitution was shown to significantly impair LIG4 function [Riballo et al. J. Biol. Chem. 276: 31124-31132 (2001)]. |
| Remarks |
Subject with pronounced radiosensitivity but normal viability and without major immune dysfunction; subject died of leukemia; cell lines from normal tissue show pronounced radiosensitivity attributable to defect in DNA ligase IV and are unable to repair DNA double strand breaks; SV40 (pSVneo) transformed cell line is GM16089; donor subject carries an arg278 to his in the LIG4 gene [ARG278HIS (R278H)], resulting from a G-to-A transition at nucleotide 833 (833G>A). |
| Liddiard K, Grimstead JW, Cleal K, Evans A, Baird DM, Tracking telomere fusions through crisis reveals conflict between DNA transcription and the DNA damage response NAR cancer3:zcaa044 2021 |
| PubMed ID: 33447828 |
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| Wilson PF, Nham PB, Urbin SS, Hinz JM, Jones IM, Thompson LH, Inter-individual variation in DNA double-strand break repair in human fibroblasts before and after exposure to low doses of ionizing radiation Mutation research683:91-7 2009 |
| PubMed ID: 19896956 |
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| Al Rashid ST, Dellaire G, Cuddihy A, Jalali F, Vaid M, Coackley C, Folkard M, Xu Y, Chen BP, Chen DJ, Lilge L, Prise KM, Bazett Jones DP, Bristow RG, Evidence for the direct binding of phosphorylated p53 to sites of DNA breaks in vivo Cancer research65:10810-21 2005 |
| PubMed ID: 16322227 |
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| Riballo E, Critchlow SE, Teo SH, Doherty AJ, Priestley A, Broughton B, Kysela
B, Beamish H, Plowman N, Arlett CF, Lehmann AR, Jackson SP, Jeggo PA, Identification of a defect in DNA ligase IV in a radiosensitive leukaemia
patient. Curr Biol9(13):699-702 1999 |
| PubMed ID: 10395545 |
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| Nelms BE, Maser RS, MacKay JF, Lagally MG, Petrini JH, In situ visualization of DNA double-strand break repair in human fibroblasts. Science280(5363):590-2 1998 |
| PubMed ID: 9554850 |
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| Badie C, Iliakis G, Foray N, Alsbeih G, Pantellias GE, Okayasu R, Cheong N, Russell NS, Begg AC, Arlett CF, et al, Defective repair of DNA double-strand breaks and chromosome damage in fibroblasts from a radiosensitive leukemia patient. Cancer Res55(6):1232-4 1995 |
| PubMed ID: 7882314 |
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| Plowman PN, Bridges BA, Arlett CF, Hinney A, Kingston JE, An instance of clinical radiation morbidity and cellular radiosensitivity, not associated with ataxia-telangiectasia. Br J Radiol63(752):624-8 1990 |
| PubMed ID: 2400879 |
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| Jaspers NG, Gatti RA, Baan C, Linssen PC, Bootsma D, Genetic complementation analysis of ataxia telangiectasia and Nijmegen breakage syndrome: a survey of 50 patients. Cytogenet Cell Genet49:259-63 1988 |
| PubMed ID: 3248383 |
| Split Ratio |
1:3 |
| Temperature |
37 C |
| Percent CO2 |
5% |
| Medium |
Eagle's Minimum Essential Medium with Earle's salts and non-essential amino acids with 2mM L-glutamine or equivalent |
| Serum |
10% fetal bovine serum Not inactivated |
| Substrate |
None specified |
| Subcultivation Method |
trypsin-EDTA |
| Supplement |
- |
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