GM01526

GM01526 LCL from B-Lymphocyte

Description:

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

Affected:

Yes

Sex:

Female

Age:

28 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

Biopsy Source

Peripheral vein

Cell Type

B-Lymphocyte

Tissue Type

Blood

Transformant

Epstein-Barr Virus

Sample Source

LCL from B-Lymphocyte

Race

White

Family Member

Relation to Proband

proband

Confirmation

Clinical summary/Case history

Species

Homo sapiens

Common Name

Human

Remarks

a T>C substitution at nucleotide 2 (2T>C) in exon 4 abolishes the initiation codon (Met1Thr); AT8BI; 46,XX,t(X;14) clone in short term lymphocytes; HLA type A9,A10,Bw17, B13(Bw40); exhibits increased chromosomal radiation sensitivity; increased chromosome breakage induced by bleomycin.

Characterizations

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 MAPPING & DOSAGE STUDIES - Y CHROMOSOME

PCR analysis of DNA from this cell culture gave a negative result with a primer for Yq11, DYS227.

Gene

ATM

Chromosomal Location

11q22.3

Allelic Variant 1

MET1THR; ATAXIA-TELANGIECTASIA

Identified Mutation

2T>C;no initiation

Phenotypic Data

Remarks

Publications

Sinha A, Saleh A, Endersby R, Yuan SH, Chokshi CR, Brown KR, Kuzio B, Kauppinen T, Singh SK, Baker SJ, McKinnon PJ, Katyal S, RAD51-Mediated DNA Homologous Recombination Is Independent of Cancers12: 2020

PubMed ID: 33138032

JunGang Z, Jun T, WanFu M, KaiMing R, FBXW7-mediated degradation of CCDC6 is impaired by ATM during DNA damage response in lung cancer cells FEBS letters586:4257-63 2012

PubMed ID: 23108047

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

Gatz SA, Keimling M, Baumann C, Dörk T, Debatin KM, Fulda S, Wiesmüller L, Resveratrol modulates DNA double-strand break repair pathways in an ATM/ATR-p53- and -Nbs1-dependent manner Carcinogenesis29:519-27 2008

PubMed ID: 18174244

Helt CE, Cliby WA, Keng PC, Bambara RA, O'Reilly MA, Ataxia telangiectasia mutated (ATM) and ATM and Rad3-related protein exhibit selective target specificities in response to different forms of DNA damage J Biol Chem280(2):1186-92 2005

PubMed ID: 15533933

Jen KY, Cheung VG, Identification of novel p53 target genes in ionizing radiation response. Cancer Res65(17):7666-73 2005

PubMed ID: 16140933

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

Tu LC, Matsui SI, Beerman TA, Hedamycin, a DNA alkylator, induces (gamma)H2AX and chromosome aberrations: involvement of phosphatidylinositol 3-kinase-related kinases and DNA replication fork movement Molecular cancer therapeutics4:1175-85 2005

PubMed ID: 16093433

Ismail IH, Nyström S, Nygren J, Hammarsten O, Activation of ataxia telangiectasia mutated by DNA strand break-inducing agents correlates closely with the number of DNA double strand breaks The Journal of biological chemistry280:4649-55 2004

PubMed ID: 15546858

Lau A, Swinbank KM, Ahmed PS, Taylor DL, Jackson SP, Smith GC, O'Connor MJ, Suppression of HIV-1 infection by a small molecule inhibitor of the ATM kinase Nature cell biology7:493-500 2004

PubMed ID: 15834407

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

Yuan JH, Feng Y, Fisher RH, Maloid S, Longo DL, Ferris DK, Polo-like kinase 1 inactivation following mitotic DNA damaging treatments is independent of ataxia telangiectasia mutated kinase Molecular cancer research : MCR2:417-26 2004

PubMed ID: 15280449

Zhu Y, Alvarez C, Doll R, Kurata H, Schebye XM, Parry D, Lees E, Intra-S-phase checkpoint activation by direct CDK2 inhibition. Mol Cell Biol24(14):6268-77 2004

PubMed ID: 15226429

Ismail IH, Mårtensson S, Moshinsky D, Rice A, Tang C, Howlett A, McMahon G, Hammarsten O, SU11752 inhibits the DNA-dependent protein kinase and DNA double-strand break repair resulting in ionizing radiation sensitization Oncogene23:873-82 2003

PubMed ID: 14661061

Hammond EM, Denko NC, Dorie MJ, Abraham RT, Giaccia AJ, Hypoxia links ATR and p53 through replication arrest. Mol Cell Biol22(6):1834-43 2002

PubMed ID: 11865061

Saito S, Goodarzi AA, Higashimoto Y, Noda Y, Lees-Miller SP, Appella E, Anderson CW, ATM mediates phosphorylation at multiple p53 sites, including Ser(46), in response to ionizing radiation. J Biol Chem277(15):12491-4 2002

PubMed ID: 11875057

Gottifredi V, Shieh S, Taya Y, Prives C, From the Cover: p53 accumulates but is functionally impaired when DNA synthesis is blocked. Proc Natl Acad Sci U S A98(3):1036-41 2001

PubMed ID: 11158590

Lin WC, Lin FT, Nevins JR, Selective induction of E2F1 in response to DNA damage, mediated by ATM-dependent phosphorylation. Genes Dev15(14):1833-44 2001

PubMed ID: 11459832

Zhao H, Spitz MR, Tomlinson GE, Zhang H, Minna JD, Wu X, Gamma-radiation-induced G2 delay, apoptosis, and p53 response as potential susceptibility markers for lung cancer. Cancer Res61(21):7819-24 2001

PubMed ID: 11691798

Borghesani PR, Alt FW, Bottaro A, Davidson L, Aksoy S, Rathbun GA, Roberts TM, Swat W, Segal RA, Gu Y, Abnormal development of Purkinje cells and lymphocytes in Atm mutant mice. Proc Natl Acad Sci U S A97:3336-41 2000

PubMed ID: 10716718

Narayan A, Tuck-Muller C, Weissbecker K, Smeets D, Ehrlich M, Hypersensitivity to radiation-induced non-apoptotic and apoptotic death in cell lines from patients with the ICF chromosome instability syndrome Mutation research456:1-15 2000

PubMed ID: 11087891

Karlseder J, Broccoli D, Dai Y, Hardy S, de Lange T, p53- and ATM-dependent apoptosis induced by telomeres lacking TRF2. Science283(5406):1321-5 1999

PubMed ID: 10037601

Myung K, Braastad C, He DM, Hendrickson EA, KARP-1 is induced by DNA damage in a p53- and ataxia telangiectasia mutated-dependent fashion. Proc Natl Acad Sci U S A95:7664-9 1998

PubMed ID: 9636207

Siliciano JD, Canman CE, Taya Y, Sakaguchi K, Appella E, Kastan MB, DNA damage induces phosphorylation of the amino terminus of p53. Genes Dev11:3471-81 1997

PubMed ID: 9407038

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

Antoccia A, Chessa L, Ricordy R, Tanzarella C, Modulation of radiation-induced chromosomal damage by inhibitors of DNA repair and flow cytometric analysis in ataxia telangiectasia cells with 'intermediate radiosensitivity'. Mutagenesis10:523-9 1995

PubMed ID: 8596472

Pandita TK, Hittelman WN, Increased initial levels of chromosome damage and heterogeneous chromosome repair in ataxia telangiectasia heterozygote cells. Mutat Res310:1-13 1994

PubMed ID: 7523872

Caporossi D, Porfirio B, Nicoletti B, Palitti F, Degrassi F, De Salvia R, Tanzarella C, Hypersensitivity of lymphoblastoid lines derived from ataxia telangiectasia patients to the induction of chromosomal aberrations by etoposide (VP-16) Mutation research290:265-72 1993

PubMed ID: 7694118

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

Cohen NA, Egorin MJ, Snyder SW, Ashar B, Wietharn BE, Pan SS, Ross DD, Hilton J, Interaction of N,N',N''-triethylenethiophosphoramide and N,N',N''- triethylenephosphoramide with cellular DNA. Cancer Res51:4360-6 1991

PubMed ID: 1714342

Hsu TC, Furlong C, The role of ethanol in oncogenesis of the upper aerodigestive tract; inhibition of DNA repair. Anticancer Res11:1995-8 1991

PubMed ID: 1776831

Metcalfe JA, Heppell-Parton A, McConville CM, Taylor AM, Characterization of a B-lymphocyte t(2;14) (p11;q32) translocation from an ataxia telangiectasia patient conferring a proliferative advantage on cells in vitro. Cytogenet Cell Genet56:91-8 1991

PubMed ID: 1901542

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

Nicotera TM, Notaro J, Notaro S, Schumer J, Sandberg AA, Elevated superoxide dismutase in Bloom's syndrome: a genetic condition of oxidative stress. Cancer Res49:5239-43 1989

PubMed ID: 2766291

Smith PJ, Makinson TA, Cellular consequences of overproduction of DNA topoisomerase II in an ataxia-telangiectasia cell line. Cancer Res49:1118-24 1989

PubMed ID: 2537142

Willis AE, Lindahl T, DNA ligase I deficiency in Bloom's syndrome. Nature325:355-7 1987

PubMed ID: 3808031

McKinnon PJ, Burgoyne LA, Evidence for the existence of an actin-derived protein in ataxia- telangiectasia lymphoblastoid cell lines. Exp Cell Res158:413-22 1985

PubMed ID: 2988987

Smith PJ, Anderson CO, Watson JV, Effects of X-irradiation and sodium butyrate on cell-cycle traverse on normal and radiosensitive lymphoblastoid cells. Exp Cell Res160:331-42 1985

PubMed ID: 2412868

Cohen MM, Simpson SJ, Increased clastogenicity and decreased inhibition of DNA synthesis by neocarzinostatin and tallysomycin in ataxia telangiectasia lymphoid cells. Mutat Res112:119-28 1983

PubMed ID: 6188042

Zwelling LA, Kerrigan D, Mattern MR, Ataxia-telangiectasia cells are not uniformly deficient in poly(ADP- ribose) synthesis following X-irradiation. Mutat Res120:69-78 1983

PubMed ID: 6835265

Cohen MM, Fruchtman CE, Simpson SJ, Martin AO, The cytogenetic response of Fanconi's anemia lymphoblastoid cell lines to various clastogens. Cytogenet Cell Genet34:230-40 1982

PubMed ID: 6183057

Cohen MM, Simpson SJ, Pazos L, Specificity of bleomycin-induced cytotoxic effects on ataxia telangiectasia lymphoid cell lines. Cancer Res41:1817-23 1981

PubMed ID: 6163529

Edwards MJ, Taylor AM, Flude EJ, Bleomycin induced inhibition of DNA synthesis in ataxia-telangiectasia cell lines. Biochem Biophys Res Commun102:610-6 1981

PubMed ID: 6171286

Huang, Genetic and biochemical studies with ataxia telangiectasia: A review. Hum Genet59:1-9 1981

PubMed ID: 10819014

Littlefield LG, Colyer SP, Joiner EE, DuFrain RJ, Frome E, Cohen MM, Chromosomal radiation sensitivity in ataxia telangiectasia long-term lymphoblastoid cell lines. Cytogenet Cell Genet31:203-13 1981

PubMed ID: 6978798

Cohen, Absence of a clastogenic factor in ataxia telangiectasia lymphoblastoid cells. Cancer Genet Cytogenet2:327-334 1980

PubMed ID: 6978798

Edwards MJ, Taylor AM, Unusual levels of (ADP-ribose)n and DNA synthesis in ataxia telangiectasia cells following gamma-ray irradiation. Nature287:745-7 1980

PubMed ID: 7432491

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

Oxford JM, Harnden DG, Parrington JM, Delhanty JD, Specific chromosome aberrations in ataxia telangiectasia. J Med Genet12:251-62 1975

PubMed ID: 1177276