Description:
ATAXIA-TELANGIECTASIA; AT
ATAXIA-TELANGIECTASIA MUTATED GENE; ATM
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Repository
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NIGMS Human Genetic Cell Repository
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| Subcollection |
Heritable Diseases
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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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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| PDL at Freeze |
4.95 |
| Passage Frozen |
18 |
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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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| REPAIR OF UV- OR X RAY-IRRADIATED DNA OR ALKYLATED DNA |
Nagasawa et al (Cancer Res 47:398-402,1987) observed that this cell culture derived from an Ataxia telangiectasia homozygote showed a hypersensitive response to the cytotoxic effects of X-irradiation. |
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| Gene |
ATM |
| Chromosomal Location |
11q22.3 |
| Allelic Variant 1 |
; ATAXIA-TELANGIECTASIA; AT |
| Identified Mutation |
c.7279_7284del (p.Leu2427_Arg2428del) |
| Remarks |
AT5BI; increased gamma-ray induced sensitivity to cell killing; see GM05849C SV40 Transformed Fibroblast; complementation group D; compound heterozygous mutation in the ATM gene; one allele is c.7278_7283delCCTTAG (p.Leu2427_Arg2428del), the other is unknown. |
| Cosentino C, Grieco D, Costanzo V, ATM activates the pentose phosphate pathway promoting anti-oxidant defence and DNA repair The EMBO journal30:546-55 2010 |
| PubMed ID: 21157431 |
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| E X, Pickering MT, Debatis M, Castillo J, Lagadinos A, Wang S, Lu S, Kowalik TF, An E2F1-mediated DNA damage response contributes to the replication of human cytomegalovirus PLoS pathogens7:e1001342 2010 |
| PubMed ID: 21589897 |
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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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| Davis T, Kipling D, Assessing the role of stress signalling via p38 MAP kinase in the premature senescence of Ataxia Telangiectasia and Werner syndrome fibroblasts Biogerontology10:253-66 2008 |
| PubMed ID: 18830681 |
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| Yan J, Yang XP, Kim YS, Jetten AM, RAP80 responds to DNA damage induced by both ionizing radiation and UV irradiation and is phosphorylated at Ser 205 Cancer research68:4269-76 2008 |
| PubMed ID: 18519686 |
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| Alterman N, Fattal-Valevski A, Moyal L, Crawford TO, Lederman HM, Ziv Y, Shiloh Y, Ataxia-telangiectasia: mild neurological presentation despite null ATM mutation and severe cellular phenotype American journal of medical genetics Part A143A:1827-34 2007 |
| PubMed ID: 17632790 |
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| Dellaire G, Ching RW, Ahmed K, Jalali F, Tse KC, Bristow RG, Bazett-Jones DP, Promyelocytic leukemia nuclear bodies behave as DNA damage sensors whose response to DNA double-strand breaks is regulated by NBS1 and the kinases ATM, Chk2, and ATR The Journal of cell biology175:55-66 2006 |
| PubMed ID: 17030982 |
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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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| Tanaka H, Mendonca MS, Bradshaw PS, Hoelz DJ, Malkas LH, Meyn MS, Gilley D, DNA damage-induced phosphorylation of the human telomere-associated protein TRF2 Proceedings of the National Academy of Sciences of the United States of America102:15539-44 2005 |
| PubMed ID: 16223874 |
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| Rogoff HA, Pickering MT, Frame FM, Debatis ME, Sanchez Y, Jones S, Kowalik TF, Apoptosis associated with deregulated E2F activity is dependent on E2F1 and Atm/Nbs1/Chk2. Mol Cell Biol24(7):2968-77 2004 |
| PubMed ID: 15024084 |
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| Shahrabani-Gargir L, Pandita TK, Werner H, Ataxia-telangiectasia mutated gene controls insulin-like growth factor I receptor gene expression in a deoxyribonucleic acid damage response pathway via mechanisms involving zinc-finger transcription factors Sp1 and WT1. Endocrinology145(12):5679-87 2004 |
| PubMed ID: 15345673 |
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| Yang J, Xu ZP, Huang Y, Hamrick HE, Duerksen-Hughes PJ, Yu YN, ATM and ATR: sensing DNA damage. World J Gastroenterol10(2):155-60 2004 |
| PubMed ID: 14716813 |
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| Itahana K, Dimri GP, Hara E, Itahana Y, Zou Y, Desprez PY, Campisi J, A role for p53 in maintaining and establishing the quiescence growth arrest in human cells. J Biol Chem277(20):18206-14 2002 |
| PubMed ID: 11880381 |
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| Tang D, Wu D, Hirao A, Lahti JM, Liu L, Mazza B, Kidd VJ, Mak TW, Ingram AJ, ERK activation mediates cell cycle arrest and apoptosis after DNA damage independently of p53. J Biol Chemepub ahead of print:18206-14 2002 |
| PubMed ID: 11821415 |
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| Balajee AS, Geard CR, Chromatin-bound PCNA complex formation triggered by DNA damage occurs independent of the ATM gene product in human cells. Nucleic Acids Res29(6):1341-51 2001 |
| PubMed ID: 11239001 |
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| Hande MP, Balajee AS, Tchirkov A, Wynshaw-Boris A, Lansdorp PM, Extra-chromosomal telomeric DNA in cells from Atm(-/-) mice and patients with ataxia-telangiectasia. Hum Mol Genet10(5):519-28 2001 |
| PubMed ID: 11181576 |
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| Keating KE, Gueven N, Watters D, Rodemann HP, Lavin MF, Transcriptional downregulation of ATM by EGF is defective in ataxia-telangiectasia cells expressing mutant protein. Oncogene20(32):4281-90 2001 |
| PubMed ID: 11466608 |
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| Wood LD, Halvorsen TL, Dhar S, Baur JA, Pandita RK, Wright WE, Hande MP, Calaf G, Hei TK, Levine F, Shay JW, Wang JJ, Pandita TK, Characterization of ataxia telangiectasia fibroblasts with extended life-span through telomerase expression. Oncogene20(3):278-88 2001 |
| PubMed ID: 11313956 |
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| Wu X, Ranganathan V, Weisman DS, Heine WF, Ciccone DN, O'Neill TB, Crick KE,
Pierce KA, Lane WS, Rathbun G, Livingston DM, Weaver DT, ATM phosphorylation of Nijmegen breakage syndrome protein is required in a DNA
damage response. Nature405(6785):477-82 2000 |
| PubMed ID: 10839545 |
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| Ashburner BP, Shackelford RE, Baldwin AS Jr, Paules RS, Lack of involvement of ataxia telangiectasia mutated (ATM) in regulation of nuclear factor-kappaB (NF-kappaB) in human diploid fibroblasts. Cancer Res59(21):5456-60 1999 |
| PubMed ID: 10554017 |
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| Piret B, Schoonbroodt S, Piette J, The ATM protein is required for sustained activation of NF-kappaB following DNA damage. Oncogene18(13):2261-71 1999 |
| PubMed ID: 10327072 |
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| Smilenov LB, Dhar S, Pandita TK, Altered telomere nuclear matrix interactions and nucleosomal periodicity in ataxia telangiectasia cells before and after ionizing radiation treatment. Mol Cell Biol19:6963-71 1999 |
| PubMed ID: 10490633 |
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| Foray N, Monroco C, Marples B, Hendry JH, Fertil B, Goodhead DT, Arlett CF, Malaise EP, Repair of radiation-induced DNA double-strand breaks in human fibroblasts is consistent with a continuous spectrum of repair probability. Int J Radiat Biol74(5):551-60 1998 |
| PubMed ID: 9848273 |
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| Gately DP, Hittle JC, Chan GK, Yen TJ, Characterization of ATM expression, localization, and associated DNA-dependent protein kinase activity. Mol Biol Cell9:2361-74 1998 |
| PubMed ID: 9725899 |
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| Hallahan DE, Dunphy E, Kuchibhotla J, Kraft A, Unlap T, Weichselbaum RR, Prolonged c-jun expression in irradiated ataxia telangiectasia fibroblasts. Int J Radiat Oncol Biol Phys36(2):355-60 1996 |
| PubMed ID: 8892460 |
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| Mirzayans R, Famulski KS, Enns L, Fraser M, Paterson MC, Characterization of the signal transduction pathway mediating gamma ray- induced inhibition of DNA synthesis in human cells: indirect evidence for involvement of calmodulin but not protein kinase C nor p53. Oncogene11:1597-605 1995 |
| PubMed ID: 7478584 |
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| Savitsky K, Bar-Shira A, Gilad S, Rotman G, Ziv Y, Vanagaite L, Tagle DA, Smith S, Uziel T, Sfez S, et al, A single ataxia telangiectasia gene with a product similar to PI-3 kinase. Science268(5218):1749-53 1995 |
| PubMed ID: 7792600 |
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| Mirzayans R, Paterson MC, Lack of correlation between hypersensitivity to cell killing and impaired inhibition of DNA synthesis in ataxia telangiectasia fibroblasts treated with 4-nitroquinoline 1-oxide. Carcinogenesis12(1):19-24 1994 |
| PubMed ID: 1899054 |
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| Raaphorst GP, Wang G, Wilkins D, Davis L, Bussey A, Stewart D, Ng CE, Evaluation of cisplatin response in three radiation resistant and three radiation sensitive cell lines. Anticancer Res14(5A):1939-42 1994 |
| PubMed ID: 7847831 |
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| Lu X, Lane DP, Differential induction of transcriptionally active p53 following UV or ionizing radiation: defects in chromosome instability syndromes? Cell75:765-78 1993 |
| PubMed ID: 8242748 |
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| Biedermann KA, Wang J, Graham RP, Brown JM, SR 4233 cytotoxicity and metabolism in DNA repair-competent and repair-deficient cell cultures. Br J Cancer63(3):358-62 1991 |
| PubMed ID: 2003976 |
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| Taylor YC, Duncan PG, Zhang X, Wright WD, Differences in the DNA supercoiling response of irradiated cell lines from ataxia-telangiectasia versus unaffected individuals. Int J Radiat Biol59:359-71 1991 |
| PubMed ID: 1671687 |
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| Taylor YC, Zhang XF, Parsian AJ, Duncan PG, Image analysis-based measurement of DNA supercoiling changes in transformed and nontransformed human cell lines. Exp Cell Res197:222-8 1991 |
| PubMed ID: 1659987 |
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| Giaccia AJ, Richardson E, Denko N, Stamato TD, Genetic analysis of XR-1 mutation in hamster and human hybrids. Somat Cell Mol Genet15(1):71-7 1989 |
| PubMed ID: 2916163 |
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| Mirzayans R, Smith BP, Paterson MC, Hypersensitivity to cell killing and faulty repair of 1-beta-D- arabinofuranosylcytosine-detectable sites in human (ataxia- telangiectasia) fibroblasts treated with 4-nitroquinoline 1-oxide. Cancer Res49:5523-9 1989 |
| PubMed ID: 2507129 |
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| Meredith MJ, Dodson ML, Imparied glutathione biosynthesis in cultured human ataxia- telangiectasia cells. Cancer Res47:4576-81 1987 |
| PubMed ID: 3621155 |
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| Nagasawa H, Kraemer KH, Shiloh Y, Little JB, Detection of ataxia telangiectasia heterozygous cell lines by postirradiation cumulative labeling index: measurements with coded samples. Cancer Res47:398-402 1987 |
| PubMed ID: 3791230 |
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| McKinnon PJ, Burgoyne LA, Altered cellular morphology and microfilament array in ataxia- telangiectasia fibroblasts. Eur J Cell Biol39:161-6 1985 |
| PubMed ID: 3910438 |
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| Mitchel RE, Chan A, Smith BP, Child SD, Paterson MC, The effects of hyperthermia and ionizing radiation in normal and ataxia telangiectasia human fibroblast lines. Radiat Res99(3):627-35 1984 |
| PubMed ID: 6473716 |
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| Arlett CF, Priestley A, Defective recovery from potentially lethal damage in some human fibroblast cell strains. Int J Radiat Biol43:157-167 1983 |
| PubMed ID: 6600729 |
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| Nagasawa H, Little JB, Comparison of kinetics of X-ray-induced cell killing in normal, ataxia telangiectasia and hereditary retinoblastoma fibroblasts. Mutat Res109:297-308 1983 |
| PubMed ID: 6843573 |
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| Barfknecht TR, Little JB, Hypersensitivity of ataxia telangiectasia skin fibroblasts to DNA alkylating agents. Mutat Res94:369-82 1982 |
| PubMed ID: 6810166 |
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| Jaspers NG, de Wit J, Regulski MR, Bootsma D, Abnormal regulation of DNA replication and increased lethality in ataxia telangiectasia cells exposed to carcinogenic agents. Cancer Res42:335-41 1982 |
| PubMed ID: 6172195 |
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| Teo IA, Arlett CF, The response of a variety of human fibroblast cell strains to the lethal effects of alkylating agents. Carcinogenesis3:33-7 1982 |
| PubMed ID: 7067035 |
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| Arlett CF, Harcourt SA, Survey of radiosensitivity in a variety of human cell strains. Cancer Res40:926-32 1980 |
| PubMed ID: 7471106 |
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| Simons JW, Development of a liquid-holding technique for the study of DNA-repair in human diploid fibroblasts. Mutat Res59(2):273-83 1979 |
| PubMed ID: 375075 |
| dbSNP |
dbSNP ID: 23187 |
| Gene Cards |
ATM |
| Gene Ontology |
GO:0003677 DNA binding |
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GO:0003700 transcription factor activity |
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GO:0004674 protein serine/threonine kinase activity |
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GO:0005622 intracellular |
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GO:0005634 nucleus |
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GO:0006281 DNA repair |
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GO:0006355 regulation of transcription, DNA-dependent |
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GO:0007131 meiotic recombination |
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GO:0007165 signal transduction |
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GO:0016740 transferase activity |
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GO:0016773 phosphotransferase activity, alcohol group as acceptor |
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GO:0045786 negative regulation of cell cycle |
| NCBI Gene |
Gene ID:472 |
| NCBI GTR |
208900 ATAXIA-TELANGIECTASIA; AT |
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607585 ATAXIA-TELANGIECTASIA MUTATED GENE; ATM |
| OMIM |
208900 ATAXIA-TELANGIECTASIA; AT |
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607585 ATAXIA-TELANGIECTASIA MUTATED GENE; ATM |
| 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 |
| Cumulative PDL at Freeze |
16.34 |
| Passage Frozen |
18 |
| Split Ratio |
1:3 |
| 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 |
| Substrate |
None specified |
| Supplement |
- |
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