GM09607
Fibroblast from Skin, Unspecified
Description:
ATAXIA-TELANGIECTASIA; AT
ATAXIA-TELANGIECTASIA MUTATED GENE; ATM
|
Repository
|
NIGMS Human Genetic Cell Repository
|
| Subcollection |
Heritable Diseases
Hereditary Cancers |
| Class |
Repair Defective and Chromosomal Instability Syndromes |
|
Biopsy Source
|
Unspecified
|
|
Cell Type
|
Fibroblast
|
|
Tissue Type
|
Skin
|
|
Transformant
|
pSVori plasmid
|
|
Sample Source
|
Fibroblast from Skin, Unspecified
|
|
Relation to Proband
|
proband
|
|
Confirmation
|
Clinical summary/Case history
|
|
Species
|
Homo sapiens
|
|
Common Name
|
Human
|
|
Remarks
|
|
| 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 |
| |
| Gene |
ATM |
| Chromosomal Location |
11q22.3 |
| Allelic Variant 1 |
TRP2769TER; ATAXIA-TELANGIECTASIA |
| Identified Mutation |
c.8307G>A (p.Trp2769Ter) |
| |
| Gene |
ATM |
| Chromosomal Location |
11q22.3 |
| Allelic Variant 2 |
11q22.3q25; ATAXIA-TELANGIECTASIA |
| Identified Mutation |
11q22.3q25 deletion |
| Remarks |
Mutation data has been reported in the literature for the untransformed line. New NGS data revealed that the donor subject is a compound heterozygote with mutations in the ATM gene (GRCh37, hg 19): c.8307 G>A (p.Trp2769Ter)(W2769X)/heterozygous, Chr:position 11: 108213987; 11q22.3q25 deletion/heterozygous; pSVori-transformed AT2SF fibroblasts; line TAT2SF; demonstrates x-ray resistant DNA synthesis and sensitivity to the lethal effects of ionizing radiation; no detectable freely replicating SV40 viral sequences; hyperdiploid karyotyped. |
| Paolacci S, Ergoren MC, De Forni D, Manara E, Poddesu B, Cugia G, Dhuli K, Camilleri G, Tuncel G, Kaya Suer H, Sultanoglu N, Sayan M, Dundar M, Beccari T, Ceccarini MR, Gunsel IS, Dautaj A, Sanlidag T, Connelly ST, Tartaglia GM, Bertelli M, In vitro and clinical studies on the efficacy of a-cyclodextrin and hydroxytyrosol against SARS-CoV-2 infection European review for medical and pharmacological sciences25:81-89 2021 |
| PubMed ID: 34890038 |
| |
| Fernández-Aroca DM, Roche O, Sabater S, Pascual-Serra R, Ortega-Muelas M, Sánchez Pérez I, Belandia B, Ruiz-Hidalgo MJ, Sánchez-Prieto R, P53 pathway is a major determinant in the radiosensitizing effect of Palbociclib: Implication in cancer therapy Cancer letters451:23-33 2018 |
| PubMed ID: 30872077 |
| |
| Boohaker RJ, Cui X, Stackhouse M, Xu B, ATM-mediated Snail Serine 100 phosphorylation regulates cellular radiosensitivity. Radiother Oncol.451:23-33 2013 |
| PubMed ID: 23891091 |
| |
| McKerlie M, Lin S, Zhu XD, ATM regulates proteasome-dependent subnuclear localization of TRF1, which is important for telomere maintenance Nucleic acids research40:3975-89 2012 |
| PubMed ID: 22266654 |
| |
| Park J, Jo YH, Cho CH, Choe W, Kang I, Baik HH, Yoon KS, ATM-deficient human fibroblast cells are resistant to low levels of DNA double-strand break induced apoptosis and subsequently undergo drug-induced premature senescence Biochemical and biophysical research communications430:429-35 2012 |
| PubMed ID: 23178571 |
| |
| Wan G, Zhang X, Langley RR, Liu Y, Hu X, Han C, Peng G, Ellis LM, Jones SN, Lu X, DNA-Damage-Induced Nuclear Export of Precursor MicroRNAs Is Regulated by the ATM-AKT Pathway Cell reports430:429-35 2012 |
| PubMed ID: 23791529 |
| |
| So EY, Ausman M, Saeki T, Ouchi T, Phosphorylation of SMC1 by ATR is required for desferrioxamine (DFO)-induced apoptosis Cell death & disease2:e128 2011 |
| PubMed ID: 21390062 |
| |
| Bacalini MG, Di Lonardo D, Catizone A, Ciccarone F, Bruno T, Zampieri M, Guastafierro T, Calabrese R, Fanciulli M, Passananti C, Caiafa P, Reale A, Poly(ADP-ribosyl)ation affects stabilization of Che-1 protein in response to DNA damage DNA repair10:380-9 2010 |
| PubMed ID: 21317046 |
| |
| 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 |
| |
| Zhang S, Zhou Y, Trusa S, Meng X, Lee EY, Lee MY, A novel DNA damage response: rapid degradation of the p12 subunit of dna polymerase delta The Journal of biological chemistry282:15330-40 2007 |
| PubMed ID: 17317665 |
| |
| Cuadrado M, Martinez-Pastor B, Murga M, Toledo LI, Gutierrez-Martinez P, Lopez E, Fernandez-Capetillo O, ATM regulates ATR chromatin loading in response to DNA double-strand breaks The Journal of experimental medicine203:297-303 2006 |
| PubMed ID: 16461339 |
| |
| Wu X, Shell SM, Yang Z, Zou Y, Phosphorylation of nucleotide excision repair factor xeroderma pigmentosum group A by ataxia telangiectasia mutated and Rad3-related-dependent checkpoint pathway promotes cell survival in response to UV irradiation Cancer research66:2997-3005 2006 |
| PubMed ID: 16540648 |
| |
| 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 |
| |
| Syljuåsen RG, Sørensen CS, Hansen LT, Fugger K, Lundin C, Johansson F, Helleday T, Sehested M, Lukas J, Bartek J, Inhibition of human Chk1 causes increased initiation of DNA replication, phosphorylation of ATR targets, and DNA breakage Molecular and cellular biology25:3553-62 2005 |
| PubMed ID: 15831461 |
| |
| Viniegra JG, Martinez N, Modirassari P, Losa JH, Parada Cobo C, Lobo VJ, Luquero CI, Alvarez-Vallina L, Ramon y Cajal S, Rojas JM, Sanchez-Prieto R, Full activation of PKB/Akt in response to insulin or ionizing radiation is mediated through ATM. J Biol Chem280(6):4029-36 2005 |
| PubMed ID: 15546863 |
| |
| Zhang Z, Ferraris JD, Irarrazabal CE, Dmitrieva NI, Park JH, Burg MB, Ataxia telangiectasia-mutated, a DNA damage-inducible kinase, contributes to high NaCl-induced nuclear localization of transcription factor TonEBP/OREBP American journal of physiology Renal physiology289:F506-11 2005 |
| PubMed ID: 15840767 |
| |
| Bilyeu JD, Panta GR, Cavin LG, Barrett CM, Turner EJ, Sweatman TW, Israel M, Lothstein L, Arsura M, Circumvention of nuclear factor kappaB-induced chemoresistance by cytoplasmic-targeted anthracyclines. Mol Pharmacol65(4):1038-47 2004 |
| PubMed ID: 15044634 |
| |
| Garg R, Callens S, Lim DS, Canman CE, Kastan MB, Xu B, Chromatin association of rad17 is required for an ataxia telangiectasia and rad-related kinase-mediated S-phase checkpoint in response to low-dose ultraviolet radiation. Mol Cancer Res2(6):362-9 2004 |
| PubMed ID: 15235112 |
| |
| Irarrazabal CE, Liu JC, Burg MB, Ferraris JD, ATM, a DNA damage-inducible kinase, contributes to activation by high NaCl of the transcription factor TonEBP/OREBP. Proc Natl Acad Sci U S A101(23):8809-14 2004 |
| PubMed ID: 15173573 |
| |
| Panta GR, Kaur S, Cavin LG, Cortes ML, Mercurio F, Lothstein L, Sweatman TW, Israel M, Arsura M, ATM and the catalytic subunit of DNA-dependent protein kinase activate NF-kappaB through a common MEK/extracellular signal-regulated kinase/p90(rsk) signaling pathway in response to distinct forms of DNA damage. Mol Cell Biol24(5):1823-35 2004 |
| PubMed ID: 14966265 |
| |
| Tosti E, Waldbaum L, Warshaw G, Gross EA, Ruggieri R, The stress kinase MRK contributes to regulation of DNA damage checkpoints through a p38gamma-independent pathway The Journal of biological chemistry279:47652-60 2004 |
| PubMed ID: 15342622 |
| |
| Cortés ML, Bakkenist CJ, Di Maria MV, Kastan MB, Breakefield XO, HSV-1 amplicon vector-mediated expression of ATM cDNA and correction of the ataxia-telangiectasia cellular phenotype Gene therapy10:1321-7 2003 |
| PubMed ID: 12883528 |
| |
| Famulski KS, Al-Hijailan RS, Dobler K, Pienkowska M, Al-Mohanna F, Paterson MC, Aberrant sensing of extracellular Ca2+ by cultured ataxia telangiectasia fibroblasts. Oncogene22(3):471-5 2003 |
| PubMed ID: 12545170 |
| |
| Ju R, Muller MT, Histone deacetylase inhibitors activate p21(WAF1) expression via ATM. Cancer Res63(11):2891-7 2003 |
| PubMed ID: 12782595 |
| |
| Mandola MV, Stoehlmacher J, Muller-Weeks S, Cesarone G, Yu MC, Lenz HJ, Ladner RD, A novel single nucleotide polymorphism within the 5' tandem repeat polymorphism of the thymidylate synthase gene abolishes USF-1 binding and alters transcriptional activity. Cancer Res63(11):2898-904 2003 |
| PubMed ID: 12782596 |
| |
| Sørensen CS, Syljuåsen RG, Falck J, Schroeder T, Rönnstrand L, Khanna KK, Zhou BB, Bartek J, Lukas J, Chk1 regulates the S phase checkpoint by coupling the physiological turnover and ionizing radiation-induced accelerated proteolysis of Cdc25A Cancer cell3:247-58 2003 |
| PubMed ID: 12676583 |
| |
| Peretz S, Jensen R, Baserga R, Glazer PM, ATM-dependent expression of the insulin-like growth factor-I receptor in a pathway regulating radiation response. Proc Natl Acad Sci U S A98(4):1676-81 2001 |
| PubMed ID: 11172010 |
| |
| Xiao J, Liu CC, Chen PL, Lee WH, RINT-1, a novel Rad50-interacting protein, participates in radiation-induced G(2)/M checkpoint control. J Biol Chem276(9):6105-11 2001 |
| PubMed ID: 11096100 |
| |
| Dong Z, Zhong Q, Chen PL, The Nijmegen breakage syndrome protein is essential for Mre11 phosphorylation upon DNA damage. J Biol Chem274:19513-6 1999 |
| PubMed ID: 10391882 |
| |
| 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 |
| |
| Rhodes N, D'Souza T, Foster CD, Ziv Y, Kirsch DG, Shiloh Y, Kastan MB, Reinhart PH, Gilmer TM, Defective potassium currents in ataxia telangiectasia fibroblasts. Genes Dev12:3686-92 1998 |
| PubMed ID: 9851975 |
| |
| Elson A, Wang Y, Daugherty CJ, Morton CC, Zhou F, Campos-Torres J, Leder P, Pleiotropic defects in ataxia-telangiectasia protein-deficient mice. Proc Natl Acad Sci U S A93:13084-9 1996 |
| PubMed ID: 8917548 |
| |
| Gilad S, Khosravi R, Shkedy D, Uziel T, Ziv Y, Savitsky K, Rotman G, Smith S, Chessa L, Jorgensen TJ, Harnik R, Frydman M, Sanal O, Portnoi S, Goldwicz Z, Jaspers NG, Gatti RA, Lenoir G, Lavin MF, Tatsumi K, Wegner RD, Shiloh Y, Bar-Shira A, Predominance of null mutations in ataxia-telangiectasia. Hum Mol Genet5(4):433-9 1996 |
| PubMed ID: 8845835 |
| |
| Hansell EJ, Frisch SM, Tremble P, Murnane JP, Werb Z, Simian virus 40 transformation alters the actin cytoskeleton, expression of matrix metalloproteinases and inhibitors of metalloproteinases, and invasive behavior of normal and ataxia- telangiectasia human skin fibroblasts. Biochem Cell Biol73:373-89 1995 |
| PubMed ID: 8703410 |
| |
| Meyn MS, High spontaneous intrachromosomal recombination rates in ataxia- telangiectasia. Science260:1327-30 1993 |
| PubMed ID: 8493577 |
| |
| Tatsumi-Miyajima J, Yagi T, Takebe H, Analysis of mutations caused by DNA double-strand breaks produced by a restriction enzyme in shuttle vector plasmids propagated in ataxia telangiectasia cells. Mutat Res294:317-23 1993 |
| PubMed ID: 7692271 |
| |
| Murnane JP, Fuller LF, Painter RB, Establishment and characterization of a permanent pSV ori--transformed ataxia-telangiectasia cell line. Exp Cell Res158:119-26 1985 |
| PubMed ID: 2987007 |
| dbSNP |
dbSNP ID: 18761 |
| Gene Cards |
ATM |
| Gene Ontology |
GO:0003677 DNA binding |
|
GO:0003700 transcription factor activity |
|
GO:0004674 protein serine/threonine kinase activity |
|
GO:0005622 intracellular |
|
GO:0005634 nucleus |
|
GO:0006281 DNA repair |
|
GO:0006355 regulation of transcription, DNA-dependent |
|
GO:0007131 meiotic recombination |
|
GO:0007165 signal transduction |
|
GO:0016740 transferase activity |
|
GO:0016773 phosphotransferase activity, alcohol group as acceptor |
|
GO:0045786 negative regulation of cell cycle |
| NCBI Gene |
Gene ID:472 |
| NCBI GTR |
208900 ATAXIA-TELANGIECTASIA; AT |
|
607585 ATAXIA-TELANGIECTASIA MUTATED GENE; ATM |
| OMIM |
208900 ATAXIA-TELANGIECTASIA; AT |
|
607585 ATAXIA-TELANGIECTASIA MUTATED GENE; ATM |
| Omim Description |
AT, COMPLEMENTATION GROUP A, INCLUDED; ATA, INCLUDED |
| |
AT, COMPLEMENTATION GROUP C, INCLUDED; ATC, INCLUDED |
| |
AT, COMPLEMENTATION GROUP D, INCLUDED; ATD, INCLUDED |
| |
AT, COMPLEMENTATION GROUP E, INCLUDED; ATE, INCLUDED |
| |
AT1 |
| |
ATAXIA-TELANGIECTASIA; AT |
| |
LOUIS-BAR SYNDROMEATAXIA-TELANGIECTASIA MUTATED, INCLUDED; ATM, INCLUDED |
| Split Ratio |
1:6 |
| 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 |
- |
|