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 |
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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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Ethnicity
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Jewish-Moroccan
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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 |
7.68 |
| Passage Frozen |
13 |
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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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| URACIL DNA GLYCOSYLASE |
Seal et al (Proc Natl Acad Sci USA 85:2339-2343, 1988) reported that monoclonal antibody, 40.10.09 to normal uracil DNA glycosylase had normal immunoreactivity with the uracil DNA glycosylase from this cell culture. In contrast, the antibody did not recognize or inhibit the native enzyme from five different Bloom syndrome cultures. |
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| Gene |
ATM |
| Chromosomal Location |
11q22.3 |
| Allelic Variant 1 |
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 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. |
| Remarks |
homozygous for the 103C>T transition in exon 5 of the ATM gene {Arg35Ter(R35X)}; fibroblasts have decreased post x-ray irradiation colony-forming ability; AT19IJE-F; decreased post-neocarzinostatin exposure colony-forming ability. |
| 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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| Ricci A, Orazi S, Biancucci F, Magnani M, Menotta M, The nucleoplasmic interactions among Lamin A/C-pRB-LAP2a-E2F1 are modulated by dexamethasone Scientific reports11:10099 2020 |
| PubMed ID: 33980953 |
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| Boudny M, Zemanova J, Khirsariya P, Borsky M, Verner J, Cerna J, Oltova A, Seda V, Mraz M, Jaros J, Jaskova Z, Spunarova M, Brychtova Y, Soucek K, Drapela S, Kasparkova M, Mayer J, Paruch K, Trbusek M, Novel CHK1 inhibitor MU380 exhibits significant single-agent activity in TP53-mutated chronic lymphocytic leukemia cells Haematologica104:2443-2455 2018 |
| PubMed ID: 30975914 |
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| Sarraf SA, Sideris DP, Giagtzoglou N, Ni L, Kankel MW, Sen A, Bochicchio LE, Huang CH, Nussenzweig SC, Worley SH, Morton PD, Artavanis-Tsakonas S, Youle RJ, Pickrell AM, PINK1/Parkin Influences Cell Cycle by Sequestering TBK1 at Damaged Mitochondria, Inhibiting Mitosis Cell reports29:225-235.e5 2018 |
| PubMed ID: 31577952 |
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| Sharma NK, Lebedeva M, Thomas T, Kovalenko OA, Stumpf JD, Shadel GS, Santos JH, Intrinsic mitochondrial DNA repair defects in Ataxia Telangiectasia DNA Repair (AMST)13:22-31 2014 |
| PubMed ID: 24342190 |
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| Hada M, Huff JL, Patel ZS, Kawata T, Pluth JM, George KA, Cucinotta FA, AT cells are not radiosensitive for simple chromosomal exchanges at low dose Mutation research716:76-83 2011 |
| PubMed ID: 21889946 |
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| Harding SM, Coackley C, Bristow RG, ATM-dependent phosphorylation of 53BP1 in response to genomic stress in oxic and hypoxic cells Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology99:307-12 2011 |
| PubMed ID: 21680038 |
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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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| Kulkarni A, Das KC, Differential roles of ATR and ATM in p53, Chk1, and histone H2AX phosphorylation in response to hyperoxia: ATR-dependent ATM activation American journal of physiology Lung cellular and molecular physiology294:L998-L1006 2008 |
| PubMed ID: 18344416 |
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| Olofsson BA, Kelly CM, Kim J, Hornsby SM, Azizkhan-Clifford J, Phosphorylation of Sp1 in response to DNA damage by ataxia telangiectasia-mutated kinase Molecular cancer research : MCR5:1319-30 2008 |
| PubMed ID: 18171990 |
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| Dauth I, Krüger J, Hofmann TG, Homeodomain-interacting protein kinase 2 is the ionizing radiation-activated p53 serine 46 kinase and is regulated by ATM Cancer research67:2274-9 2007 |
| PubMed ID: 17332358 |
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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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| Kim HS, Li H, Cevher M, Parmelee A, Fonseca D, Kleiman FE, Lee SB, DNA damage-induced BARD1 phosphorylation is critical for the inhibition of messenger RNA processing by BRCA1/BARD1 complex Cancer research66:4561-5 2006 |
| PubMed ID: 16651405 |
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| Pusapati RV, Rounbehler RJ, Hong S, Powers JT, Yan M, Kiguchi K, McArthur MJ, Wong PK, Johnson DG, ATM promotes apoptosis and suppresses tumorigenesis in response to Myc Proceedings of the National Academy of Sciences of the United States of America103:1446-51 2006 |
| PubMed ID: 16432227 |
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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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| Kim JS, Krasieva TB, Kurumizaka H, Chen DJ, Taylor AM, Yokomori K, Independent and sequential recruitment of NHEJ and HR factors to DNA damage sites in mammalian cells The Journal of cell biology170:341-7 2005 |
| PubMed ID: 16061690 |
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| Lilley CE, Carson CT, Muotri AR, Gage FH, Weitzman MD, DNA repair proteins affect the lifecycle of herpes simplex virus 1 Proceedings of the National Academy of Sciences of the United States of America102:5844-9 2005 |
| PubMed ID: 15824307 |
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| Boutell C, Everett RD, Herpes simplex virus type 1 infection induces the stabilization of p53 in a USP7- and ATM-independent manner. J Virol78(15):8068-77 2004 |
| PubMed ID: 15254178 |
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| Carson CT, Schwartz RA, Stracker TH, Lilley CE, Lee DV, Weitzman MD, The Mre11 complex is required for ATM activation and the G2/M checkpoint. EMBO J22(24):6610-20 2003 |
| PubMed ID: 14657032 |
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| Ha L, Ceryak S, Patierno SR, Chromium (VI) activates ataxia telangiectasia mutated (ATM) protein. Requirement
of ATM for both apoptosis and recovery from terminal growth arrest. J Biol Chem278(20):17885-94 2003 |
| PubMed ID: 12637545 |
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| Mamon HJ, Dahlberg W, Azzam EI, Nagasawa H, Muto MG, Little JB, Differing effects of breast cancer 1, early onset (BRCA1) and ataxia-telangiectasia mutated (ATM) mutations on cellular responses to ionizing radiation. Int J Radiat Biol79(10):817-29 2003 |
| PubMed ID: 14630541 |
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| Jakob B, Scholz M, Taucher-Scholz G, Characterization of CDKN1A (p21) binding to sites of heavy-ion-induced damage: colocalization with proteins involved in DNA repair International journal of radiation biology78:75-88 2002 |
| PubMed ID: 11779358 |
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| Kim JS, Krasieva TB, LaMorte V, Taylor AM, Yokomori K, Specific recruitment of human cohesin to laser-induced DNA damage. J Biol Chem277(47):45149-53 2002 |
| PubMed ID: 12228239 |
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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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| Shackelford RE, Innes CL, Sieber SO, Heinloth AN, Leadon SA, Paules RS, The Ataxia telangiectasia gene product is required for oxidative stress-induced G1 and G2 checkpoint function in human fibroblasts. J Biol Chem276(24):21951-9 2001 |
| PubMed ID: 11290740 |
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| Van PL, Yim KW, Jin DY, Dapolito G, Kurimasa A, Jeang KT, Genetic evidence of a role for ATM in functional interaction between human T-cell leukemia virus type 1 Tax and p53. J Virol75(1):396-407 2001 |
| PubMed ID: 11119608 |
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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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| de Toledo SM, Azzam EI, Dahlberg WK, Gooding TB, Little JB, ATM complexes with HDM2 and promotes its rapid phosphorylation in a p53-independent manner in normal and tumor human cells exposed to ionizing radiation. Oncogene19(54):6185-93 2000 |
| PubMed ID: 11175332 |
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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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| Vaziri H, West MD, Allsopp RC, Davison TS, Wu YS, Arrowsmith CH, Poirier GG, Benchimol S, ATM-dependent telomere loss in aging human diploid fibroblasts and DNA damage lead to the post-translational activation of p53 protein involving poly(ADP-ribose) polymerase. EMBO J16:6018-33 1997 |
| PubMed ID: 9312059 |
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| Gilad S, Bar-Shira A, Harnik R, Shkedy D, Ziv Y, Khosravi R, Brown K, Vanagaite L, Xu G, Frydman M, Lavin MF, Hill D, Tagle DA, Shiloh Y, Ataxia-telangiectasia: founder effect among north African Jews. Hum Mol Genet5:2033-7 1996 |
| PubMed ID: 8968760 |
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| Dahlberg, Response of dermal fibroblast cultures from patients eith unusually severe responses to radiotherapy and from ataxia telangiectasia heterozygotes to fractionated radiation. Clin Cancer Res1:785 (1995):2033-7 1995 |
| PubMed ID: 8968760 |
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| Li CY, Nagasawa H, Dahlberg WK, Little JB, Diminished capacity for p53 in mediating a radiation-induced G1 arrest in established human tumor cell lines. Oncogene11:1885-92 1995 |
| PubMed ID: 7478618 |
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| Nagasawa H, Keng P, Harley R, Dahlberg W, Little JB, Relationship between gamma-ray-induced G2/M delay and cellular radiosensitivity. Int J Radiat Biol66(4):373-9 1994 |
| PubMed ID: 7930839 |
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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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| Fukunaga N, Burrows HL, Meyers M, Schea RA, Boothman DA, Enhanced induction of tissue-type plasminogen activator in normal human cells compared to cancer-prone cells following ionizing radiation. Int J Radiat Oncol Biol Phys24(5):949-57 1992 |
| PubMed ID: 1447036 |
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| Nagasawa H, Little JB, Tsang NM, Saunders E, Tesmer J, Strniste GF, Effect of dose rate on the survival of irradiated human skin fibroblasts. Radiat Res132:375-9 1992 |
| PubMed ID: 1475361 |
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| Kochevar IE, Walsh AA, Green HA, Sherwood M, Shih AG, Sutherland BM, DNA damage induced by 193-nm radiation in mammalian cells. Cancer Res51:288-93 1991 |
| PubMed ID: 1988091 |
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| Boothman DA, Bouvard I, Hughes EN, Identification and characterization of X-ray-induced proteins in human cells. Cancer Res49:2871-8 1989 |
| PubMed ID: 2720648 |
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| Bender MA, Viola MV, Fiore J, Thompson MH, Leonard RC, Normal G2 chromosomal radiosensitivity and cell survival in the cancer family syndrome [see comments] Cancer Res48:2579-84 1988 |
| PubMed ID: 3356018 |
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| Gomer CJ, Rucker N, Murphree AL, Differential cell photosensitivity following porphyrin photodynamic therapy. Cancer Res48:4539-42 1988 |
| PubMed ID: 2969280 |
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| Seal G, Brech K, Karp SJ, Cool BL, Sirover MA, Immunological lesions in human uracil DNA glycosylase: association with Bloom syndrome. Proc Natl Acad Sci U S A85:2339-43 1988 |
| PubMed ID: 3353381 |
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| Fornace AJ Jr, Kinsella TJ, Dobson PP, Mitchell JB, Repair of ionizing radiation DNA base damage in ataxia-telangiectasia cells. Cancer Res46:1703-6 1986 |
| PubMed ID: 3004702 |
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| Cornforth MN, Bedford JS, On the nature of a defect in cells from individuals with ataxia- telangiectasia. Science227:1589-91 1985 |
| PubMed ID: 3975628 |
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| Hayashi A, Yoshida Y, Tanaka H, Arima M, Ohno K, Variable radiosensitivity in fibroblasts from patients with tuberous sclerosis. J Invest Dermatol84:77-8 1985 |
| PubMed ID: 3965582 |
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| Boorstein RJ, Pardee AB, Factors modifying 3-aminobenzamide cytotoxicity in normal and repair- deficient human fibroblasts. J Cell Physiol120:335-44 1984 |
| PubMed ID: 6746752 |
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| Boorstein R, Campisi J, Pardee AB, The study of DNA-repair defects using [125I]iododeoxycytidine incorporation as an assay for the growth of herpes simplex virus. Mutat Res112:85-95 1983 |
| PubMed ID: 6300669 |
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| Chan GL, Little JB, Cultured diploid fibroblasts from patients with the nevoid basal cell carcinoma syndrome are hypersensitive to killing by ionizing radiation. Am J Pathol111:50-5 1983 |
| PubMed ID: 6837723 |
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| Povirk LF, Goldberg IH, Inhibition of mammalian deoxyribonucleic acid synthesis by neocarzinostatin: selective effect on replicon initiation in CHO cells and resistant synthesis in ataxia telangiectasia fibroblasts. Biochemistry21:5857-62 1982 |
| PubMed ID: 6217834 |
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| Shiloh Y, Tabor E, Becker Y, Cellular hypersensitivity to neocarzinostatin in ataxia-telangiectasia skin fibroblasts. Cancer Res42:2247-9 1982 |
| PubMed ID: 6210429 |
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| Zamansky GB, Little JB, Survival of 60Co-irradiated herpes simplex virus in 15 human diploid fibroblast cell strains. Mutat Res94:245-55 1982 |
| PubMed ID: 6287252 |
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| Chan GL, Little JB, Cross-sensitivity of certain xeroderma pigmentosum and Cockayne syndrome fibroblast strains to both ionizing radiation and ultraviolet light. Mol Gen Genet181:562-3 1981 |
| PubMed ID: 6943407 |
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| Hohmann P, Species- and cell-specific expression of H1 histones in tissue culture cells. Arch Biochem Biophys205:198-209 1980 |
| PubMed ID: 7447476 |
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| Cohen MM, Sagi M, Ben-Zur Z, Schaap T, Voss R, Kohn G, Ben-Bassat H, Ataxia telangiectasia: chromosomal stability in continuous lymphoblastoid cell lines. Cytogenet Cell Genet23:44-52 1979 |
| PubMed ID: 761484 |
| dbSNP |
dbSNP ID: 10479 |
| 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 |
26.4 |
| Passage Frozen |
13 |
| Split Ratio |
1:5 |
| Temperature |
37 C |
| Percent CO2 |
5% |
| Percent O2 |
3% |
| 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 |
| Supplement |
- |
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