Description:
ATAXIA-TELANGIECTASIA; AT
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Repository
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NIGMS Human Genetic Cell Repository
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| Subcollection |
Heritable Diseases
Hereditary Cancers
Chromosome Abnormalities |
| Class |
Repair Defective and Chromosomal Instability Syndromes |
| Class |
Syndromes with Increased Chromosome Breakage |
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Cell Type
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Fibroblast
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Transformant
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Untransformed
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Race
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White
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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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| PDL at Freeze |
4.1 |
| Passage Frozen |
15 |
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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 and by Chromosome Analysis |
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| REPAIR OF UV- OR X RAY-IRRADIATED DNA OR ALKYLATED DNA |
Bennett & Rainbow (Mutagenesis 3:389-395,1988) examined the UV-enhanced reactivation (UVER) and UV-enhanced mutagenesis (UVEM) of UVirradiated adenovirus in AT fibroblasts. UVER was examined using both V antigen expression as well as progeny production from infected cultures. Viral mutagenesis was studied by examining the induction of phenotypically wild-type revertants among the progeny obtained from fibroblasts infected with a temperature-sensitive early mutant of adenovirus (Ad5ts36). UVER factors for Ad V antigen expression were significantly less than normal in the AT strains tested when infection occurred immediately after UV-irradiation of cells. However, UVER factors were >1 and similar to those found for normal strains when cells were infected 24 h after UV-irradiation, indicating a delay in the expression of UVER for Ad V antigen in AT cells. UV-irradiation of both normal and AT cells 24 h prior to infection also resulted in a significant increase in progeny survival for UV-irradiated Ad. In normal cells, this progeny UVER was concomitant with a significant increase in the mutation frequency for UV-irradiated virus (increase in targeted mutagenesis) suggesting the existence of an inducible errorprone DNA repair mode in normal human cells. In contrast, pre-UV-irradiation of AT cells resulted in a significant decrease in the mutation frequency for UV-irradiated virus. These results suggest that AT cells lack an inducible error-prone DNA mode and that the delayed expression of UVER in AT cells results from a relatively error-free mechanism. |
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| Gene |
ATM |
| Chromosomal Location |
11q22.3 |
| Allelic Variant 2 |
607585.0008; ATAXIA-TELANGIECTASIA |
| Identified Mutation |
ARG35TER; Gilad et al. [Hum. Molec. Genet. 5: 2033 (1996)] reported that a single AT mutation was observed in 32 of 33 defective ATM alleles in Jewish AT families of North African origin, coming from various regions of Morocco and Tunisia. This mutation, a 103C-T transition, results in a stop codon at position 35 of the ATM protein. No ATM protein could be detected in cells from patients with this mutation. Gilad et al. (1996) developed a rapid carrier detection assay for this mutation suitable for population-based screening. |
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| Gene |
ATM |
| Chromosomal Location |
11q22.3 |
| Allelic Variant 8 |
607585.0008; ATAXIA-TELANGIECTASIA |
| Identified Mutation |
ARG35TER; Gilad et al. [Hum. Molec. Genet. 5: 2033 (1996)] reported that a single AT mutation was observed in 32 of 33 defective ATM alleles in Jewish AT families of North African origin, coming from various regions of Morocco and Tunisia. This mutation, a 103C-T transition, results in a stop codon at position 35 of the ATM protein. No ATM protein could be detected in cells from patients with this mutation. Gilad et al. (1996) developed a rapid carrier detection assay for this mutation suitable for population-based screening. |
| Remarks |
46,XY; clinically affected. Homozygous for ATM gene mutation ATM:c.103C>T (rs55861249); ARG35TER [mutation verified in GM01588 cell line by an external investigator]. |
| Liu X, Hu M, Liu P, Jiao M, Zhou M, Lee AK, Li F, Li CY, ATM Paradoxically Promotes Oncogenic Transformation via Transcriptional Reprogramming Cancer research: 2020 |
| PubMed ID: 32060145 |
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| O'Hagan HM, Ljungman M, Phosphorylation and nuclear accumulation are distinct events contributing to the activation of p53. Mutat Res546(1-2):7-15 2004 |
| PubMed ID: 14757188 |
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| Alsbeih G, Brock WA, Terry N, Story MD, Analysis of radiation-induced DNA double-strand breaks misrepair is not compromized by broken DNA in human fibroblasts Radiation and environmental biophysics42:107-11 2003 |
| PubMed ID: 12802598 |
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| Adamson AW, Kim WJ, Shangary S, Baskaran R, Brown KD, ATM is activated in response to N-methyl-N'-nitro-N-nitrosoguanidine-induced DNA
alkylation. J Biol Chem277(41):38222-9 2002 |
| PubMed ID: 12151394 |
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| Bennett CB, Rainbow AJ, Delayed expression of enhanced reactivation and decreased mutagenesis of UV-irradiated adenovirus in UV-irradiated ataxia telangiectasia fibroblasts. Mutagenesis3:389-95 1988 |
| PubMed ID: 3070272 |
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| Hurt MM, Moses RE, Conversion of replicative intermediates in human DNA-repair defective cells. Exp Cell Res163:396-404 1986 |
| PubMed ID: 3956584 |
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| Jeeves WP, Rainbow AJ, An aberration in gamma-ray-enhanced reactivation of irradiated adenovirus in ataxia telangiectasia fibroblasts. Carcinogenesis7:381-7 1986 |
| PubMed ID: 3948323 |
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| Hurt MM, Beaudet AL, Moses RE, Stable low molecular weight DNA in xeroderma pigmentosum cells. Proc Natl Acad Sci U S A80:6987-91 1983 |
| PubMed ID: 6196782 |
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| Huang, Genetic and biochemical studies with ataxia telangiectasia: A review. Hum Genet59:1-9 1981 |
| PubMed ID: 10819014 |
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| Moses RE, Beaudet AL, Apurinic DNA endonuclease activities in repair-deficient human cell lines. Nucleic Acids Res5:463-73 1978 |
| PubMed ID: 634794 |
| dbSNP |
dbSNP ID: 22381 |
| NCBI GTR |
208900 ATAXIA-TELANGIECTASIA; AT |
| OMIM |
208900 ATAXIA-TELANGIECTASIA; AT |
| Omim Description |
AT, COMPLEMENTATION GROUP A, INCLUDED; ATA, INCLUDED |
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AT, COMPLEMENTATION GROUP C, INCLUDED; ATC, INCLUDED |
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AT, COMPLEMENTATION GROUP D, INCLUDED; ATD, INCLUDED |
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AT, COMPLEMENTATION GROUP E, INCLUDED; ATE, INCLUDED |
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AT1 |
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ATAXIA-TELANGIECTASIA; AT |
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LOUIS-BAR SYNDROMEATAXIA-TELANGIECTASIA MUTATED, INCLUDED; ATM, INCLUDED |
| Passage Frozen |
15 |
| Split Ratio |
1:4 |
| Temperature |
37 C |
| Percent CO2 |
5% |
| Percent O2 |
AMBIENT |
| Medium |
Eagle's Minimum Essential Medium with Earle's salts and non-essential amino acids with 2mM L-glutamine or equivalent |
| Serum |
15% fetal bovine serum Not inactivated |
| Supplement |
- |
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