NA02052

NA02052 DNA from Fibroblast

Description:

ATAXIA-TELANGIECTASIA; AT
ATAXIA-TELANGIECTASIA MUTATED GENE; ATM

Affected:

Yes

Sex:

Female

Age:

15 YR (At Sampling)

Overview

Repository

NIGMS Human Genetic Cell Repository

Subcollection

Heritable Diseases
Hereditary Cancers
Chromosome Abnormalities

Class

Repair Defective and Chromosomal Instability Syndromes

Class

Syndromes with Increased Chromosome Breakage

Quantity

0.050mg

Quantitation Method

Please see our FAQ

Cell Type

Fibroblast

Transformant

Untransformed

Sample Source

DNA from Fibroblast

Race

White

Ethnicity

Jewish-Moroccan

Relation to Proband

proband

Confirmation

Clinical summary/Case history

Species

Homo sapiens

Common Name

Human

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.

Characterizations

PDL at Freeze

7.68

Passage Frozen

IDENTIFICATION OF SPECIES OF ORIGIN

Species of Origin Confirmed by Nucleoside Phosphorylase, Glucose-6-Phosphate Dehydrogenase, and Lactate Dehydrogenase Isoenzyme Electrophoresis

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.

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.

Gene

ATM

Chromosomal Location

11q22.3

Allelic Variant 2

607585.0008; ATAXIA-TELANGIECTASIA

Identified Mutation

Phenotypic Data

Remarks

Publications

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Gomer CJ, Rucker N, Murphree AL, Differential cell photosensitivity following porphyrin photodynamic therapy. Cancer Res48:4539-42 1988

PubMed ID: 2969280

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

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

Cornforth MN, Bedford JS, On the nature of a defect in cells from individuals with ataxia- telangiectasia. Science227:1589-91 1985

PubMed ID: 3975628

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

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

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

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

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

Shiloh Y, Tabor E, Becker Y, Cellular hypersensitivity to neocarzinostatin in ataxia-telangiectasia skin fibroblasts. Cancer Res42:2247-9 1982

PubMed ID: 6210429

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

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

Hohmann P, Species- and cell-specific expression of H1 histones in tissue culture cells. Arch Biochem Biophys205:198-209 1980

PubMed ID: 7447476

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