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
Hereditary Cancers
Chromosome Abnormalities |
| Class |
Repair Defective and Chromosomal Instability Syndromes |
| Class |
Syndromes with Increased Chromosome Breakage |
| Quantity |
25 µg |
| Quantitation Method |
Please see our FAQ |
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Biopsy Source
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Peripheral vein
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Cell Type
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B-Lymphocyte
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Tissue Type
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Blood
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Transformant
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Epstein-Barr Virus
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Sample Source
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DNA from LCL
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Race
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White
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Family Member
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3
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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 MAPPING & DOSAGE STUDIES - Y CHROMOSOME |
PCR analysis of DNA from this cell culture gave a positive result with a primer for Yq11, DYS227. |
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| Gene |
ATM |
| Chromosomal Location |
11q22.3 |
| Allelic Variant 1 |
LYS2756TER; ATAXIA-TELANGIECTASIA |
| Identified Mutation |
8266A>T |
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| Gene |
ATM |
| Chromosomal Location |
11q22.3 |
| Allelic Variant 2 |
S381fsX; ATAXIA-TELANGIECTASIA |
| Identified Mutation |
1141ins4 |
| Remarks |
AT4Be; clinically affected; neurological abnormalities; lymphoid culture shows hypersensitivity to X-irradiation; compound heterozygote; the maternal allele carries an A>T substitution at nucleotide 8266 (8266A>T) in exon 58 resulting in a truncation at codon 2756 [Lys2756Ter (K2756X)] and the paternal allele carries a 4bp insertion at nucleotide 1141 in exon 11 resulting in a frameshift at codon 381 leading to a truncation (S381fsX); similarly affected sibling (not in repository); 3 other unaffected sibilings are in repository (see family 516); father(GM03187-LCL/GM03488-Fibro) and mother(GM03188-LCL/GM03489-Fibro) are unaffected carriers; see GM03487 for donor Fibroblast; |
| Dietz A, Subedi P, Azimzadeh O, Duchrow L, Kaestle F, Paetzold J, Katharina Payer S, Hornhardt S, von Toerne C, Hauck SM, Kempkes B, Kuklik-Roos C, Brandes D, Borkhardt A, Moertl S, Gomolka M, The Chromosome Passenger Complex (CPC) Components and Its Associated Pathways Are Promising Candidates to Differentiate Between Normosensitive and Radiosensitive ATM-Mutated Cells Biomarker insights19:11772719241274017 2024 |
| PubMed ID: 39493730 |
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| Caballero M, Ge T, Rebelo AR, Seo S, Kim S, Brooks K, Zuccaro M, Kanagaraj R, Vershkov D, Kim D, Smogorzewska A, Smolka M, Benvenisty N, West SC, Egli D, Mace EM, Koren A, Comprehensive analysis of DNA replication timing across 184 cell lines suggests a role for MCM10 in replication timing regulation Human molecular genetics19:11772719241274017 2021 |
| PubMed ID: 35394024 |
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| Asumen MG, Ifeacho TV, Cockerham L, Pfandl C, Wall NR, Dynamic changes to survivin subcellular localization are initiated by DNA damage OncoTargets and therapy3:129-37 2010 |
| PubMed ID: 20856848 |
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| Boehme KA, Kulikov R, Blattner C, p53 stabilization in response to DNA damage requires Akt/PKB and DNA-PK Proceedings of the National Academy of Sciences of the United States of America105:7785-90 2008 |
| PubMed ID: 18505846 |
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| Pennarun G, Granotier C, Hoffschir F, Mandine E, Biard D, Gauthier LR, Boussin FD, Role of ATM in the telomere response to the G-quadruplex ligand 360A Nucleic acids research36:1741-54 2008 |
| PubMed ID: 18263609 |
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| Griffith E, Walker S, Martin CA, Vagnarelli P, Stiff T, Vernay B, Al Sanna N, Saggar A, Hamel B, Earnshaw WC, Jeggo PA, Jackson AP, O'Driscoll M, Mutations in pericentrin cause Seckel syndrome with defective ATR-dependent DNA damage signaling Nature genetics40:232-6 2007 |
| PubMed ID: 18157127 |
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| Ho CC, Siu WY, Lau A, Chan WM, Arooz T, Poon RY, Stalled replication induces p53 accumulation through distinct mechanisms from DNA damage checkpoint pathways Cancer research66:2233-41 2006 |
| PubMed ID: 16489026 |
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| Innes CL, Heinloth AN, Flores KG, Sieber SO, Deming PB, Bushel PR, Kaufmann WK, Paules RS, ATM requirement in gene expression responses to ionizing radiation in human lymphoblasts and fibroblasts. Mol Cancer Res4(3):197-207 2006 |
| PubMed ID: 16547157 |
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| Jen KY, Cheung VG, Identification of novel p53 target genes in ionizing radiation response. Cancer Res65(17):7666-73 2005 |
| PubMed ID: 16140933 |
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| Marcelain K, De La Torre C, González P, Pincheira J, Roles of nibrin and AtM/ATR kinases on the G2 checkpoint under endogenous or radio-induced DNA damage Biological research38:179-85 2005 |
| PubMed ID: 16238096 |
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| Stiff T, Reis C, Alderton GK, Woodbine L, O'Driscoll M, Jeggo PA, Nbs1 is required for ATR-dependent phosphorylation events. EMBO J24(1):199-208 2005 |
| PubMed ID: 15616588 |
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| Alderton GK, Joenje H, Varon R, Borglum AD, Jeggo PA, O'Driscoll M, Seckel syndrome exhibits cellular features demonstrating defects in the ATR-signalling pathway. Hum Mol Genet13(24):3127-38 2004 |
| PubMed ID: 15496423 |
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| Leonard JC, Mullinger AM, Schmidt J, Cordell HJ, Johnson RT, Genome instability in ataxia telangiectasia (A-T) families: camptothecin-induced damage to replicating DNA discriminates between obligate A-T heterozygotes, A-T homozygotes and controls. Biosci Rep24(6):617-29 2004 |
| PubMed ID: 16158199 |
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| Ng CP, Lee HC, Ho CW, Arooz T, Siu WY, Lau A, Poon RY, Differential mode of regulation of the checkpoint kinases CHK1 and CHK2 by their regulatory domains. J Biol Chem279(10):8808-19 2004 |
| PubMed ID: 14681223 |
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| Siu WY, Lau A, Arooz T, Chow JP, Ho HT, Poon RY, Topoisomerase poisons differentially activate DNA damage checkpoints through ataxia-telangiectasia mutated-dependent and -independent mechanisms. Mol Cancer Ther3(5):621-32 2004 |
| PubMed ID: 15141020 |
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| Angele S, Romestaing P, Moullan N, Vuillaume M, Chapot B, Friesen M, Jongmans W, Cox DG, Pisani P, Gerard JP, Hall J, ATM haplotypes and cellular response to DNA damage: association with breast cancer risk and clinical radiosensitivity. Cancer Res63(24):8717-25 2003 |
| PubMed ID: 14695186 |
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| Chow JP, Siu WY, Fung TK, Chan WM, Lau A, Arooz T, Ng CP, Yamashita K, Poon RY, DNA damage during the spindle-assembly checkpoint degrades CDC25A, inhibits cyclin-CDC2 complexes, and reverses cells to interphase. Mol Biol Cell14(10):3989-4002 2003 |
| PubMed ID: 14517313 |
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| Pichierri P, Rosselli F, Franchitto A, Werner's syndrome protein is phosphorylated in an ATR/ATM-dependent manner following replication arrest and DNA damage induced during the S phase of the cell cycle Oncogene22:1491-500 2003 |
| PubMed ID: 12629512 |
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| Wang W, Takimoto R, Rastinejad F, El-Deiry WS, Stabilization of p53 by CP-31398 inhibits ubiquitination without altering
phosphorylation at serine 15 or 20 or MDM2 binding. Mol Cell Biol23(6):2171-81 2003 |
| PubMed ID: 12612087 |
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| Franchitto A, Pichierri P, Bloom's syndrome protein is required for correct relocalization of RAD50/MRE11/NBS1 complex after replication fork arrest. J Cell Biol157(1):19-30 2002 |
| PubMed ID: 11916980 |
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| Deming PB, Cistulli CA, Zhao H, Graves PR, Piwnica-Worms H, Paules RS, Downes CS, Kaufmann WK, The human decatenation checkpoint. Proc Natl Acad Sci U S A98(21):12044-9 2001 |
| PubMed ID: 11593014 |
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| Dantzer F, Menissier-de Murcia J, Barlow C, Wynshaw-Boris A, de Murcia G, Poly(ADP-ribose) polymerase activity is not affected in ataxia telangiectasia cells and knockout mice. Carcinogenesis20:177-80 1999 |
| PubMed ID: 9934867 |
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| Will O, Mahler HC, Arrigo AP, Epe B, Influence of glutathione levels and heat-shock on the steady-state levels of oxidative DNA base modifications in mammalian cells. Carcinogenesis20:333-7 1999 |
| PubMed ID: 10069473 |
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| Hacia JG, Sun B, Hunt N, Edgemon K, Mosbrook D, Robbins C, Fodor SP, Tagle DA, Collins FS, Strategies for mutational analysis of the large multiexon ATM gene using high-density oligonucleotide arrays. Genome Res8(12):1245-58 1998 |
| PubMed ID: 9872980 |
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| Sasaki T, Tian H, Kukita Y, Inazuka M, Tahira T, Imai T, Yamauchi M, Saito T, Hori T, Hashimoto-Tamaoki T, Komatsu K, Nikaido O, Hayashi K, ATM mutations in patients with ataxia telangiectasia screened by a hierarchical strategy. Hum Mutat12(3):186-95 1998 |
| PubMed ID: 9711876 |
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| Concannon P, Gatti RA, Diversity of ATM gene mutations detected in patients with ataxia-telangiectasia. Hum Mutat10(2):100-7 1997 |
| PubMed ID: 9259193 |
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| Jongmans W, Vuillaume M, Chrzanowska K, Smeets D, Sperling K, Hall J, Nijmegen breakage syndrome cells fail to induce the p53-mediated DNA damage response following exposure to ionizing radiation. Mol Cell Biol17(9):5016-22 1997 |
| PubMed ID: 9271379 |
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| Wei S, Charmley P, Concannon P, Organization, polymorphism, and expression of the human T-cell receptor AV1
subfamily. Immunogenetics45(6):405-12 1997 |
| PubMed ID: 9089098 |
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| Chen G, Lee EYHP, The product of the ATM gene is a 370-kDa nuclear phosphoprotein. J Biol Chem271:33693-7 1996 |
| PubMed ID: 8969240 |
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| Telatar M, Wang Z, Udar N, Liang T, Bernatowska-Matuszkiewicz E, Lavin M, Shiloh Y, Concannon P, Good RA, Gatti RA, Ataxia-telangiectasia: mutations in ATM cDNA detected by protein- truncation screening. Am J Hum Genet59:40-4 1996 |
| PubMed ID: 8659541 |
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| Wright J, Teraoka S, Onengut S, Tolun A, Gatti RA, Ochs HD, Concannon P, A high frequency of distinct ATM gene mutations in ataxia- telangiectasia. Am J Hum Genet59:839-46 1996 |
| PubMed ID: 8808599 |
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| Kastan MB, Zhan Q, el-Deiry WS, Carrier F, Jacks T, Walsh WV, Plunkett BS, Vogelstein B, Fornace AJ Jr, A mammalian cell cycle checkpoint pathway utilizing p53 and GADD45 is defective in ataxia-telangiectasia. Cell71:587-97 1992 |
| PubMed ID: 1423616 |
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| Karam LR, Calsou P, Franklin WA, Painter RB, Olsson M, Lindahl T, Modification of deoxyribose-phosphate residues by extracts of ataxia telangiectasia cells. Mutat Res236:19-26 1990 |
| PubMed ID: 2366795 |
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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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| Berliner N, Duby AD, Morton CC, Leder P, Seidman JG, Detection of a frequent restriction fragment length polymorphism in the human T cell antigen receptor beta chain locus. A potential diagnostic tool. J Clin Invest76:1283-5 1985 |
| PubMed ID: 2995449 |
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| Kraemer KH, Soares N, Waters HL, Bustin M, Effect of X-radiation on DNA and histone synthesis in ataxia telangiectasia and normal lymphoblastoid cells. Mutat Res112:359-67 1983 |
| PubMed ID: 6656798 |
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| Kohn PH, Kraemer KH, Buchanan JK, Influence of ataxia telangiectasia gene dosage on bleomycin-induced chromosome breakage and inhibition of replication in human lymphoblastoid cell lines. Exp Cell Res137:387-95 1982 |
| PubMed ID: 6173245 |
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| Kraemer KH, Waters HL, Buchanan JK, Survival of human lymphoblastoid cells after DNA damage measured by growth in microtiter wells. Mutat Res72:285-94 1980 |
| PubMed ID: 6160397 |
| dbSNP |
dbSNP ID: 10618 |
| 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 |
| GEO |
GEO Accession No: GSM1116569 |
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GEO Accession No: GSM1116570 |
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GEO Accession No: GSM1116637 |
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GEO Accession No: GSM1116638 |
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GEO Accession No: GSM1116639 |
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GEO Accession No: GSM1116640 |
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GEO Accession No: GSM478628 |
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GEO Accession No: GSM478629 |
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GEO Accession No: GSM71336 |
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GEO Accession No: GSM71337 |
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GEO Accession No: GSM71338 |
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GEO Accession No: GSM71339 |
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GEO Accession No: GSM71340 |
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GEO Accession No: GSM71341 |
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GEO Accession No: GSM71342 |
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GEO Accession No: GSM71343 |
| 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 |
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