Ataxia telangiectasia syndrome: moonlighting ATM

References

• Syllaba L, Henner K. Contributions to the independence of idiopathic and congenital double athetosis. Rev Neurol. 1926;1:541–562.
   Google Scholar
• Louis-Bar D. Sur syndrome progressif comprenant des telangiectasies capillaires cutanees et conjonctivales symetriques, a disposition naevoide et de troubles cerebelleux. Confin Neurol (Basel). 1941;4:32–42.
   Google Scholar
• Boder E, Sedgwick RP. Ataxia-telangiectasia; a familial syndrome of progressive cerebellar ataxia, oculocutaneous telangiectasia and frequent pulmonary infection. Pediatrics. 1958 Apr;21(4):526–554.
   PubMed Web of Science ®Google Scholar
• Teive HA, Moro A, Moscovich M, et al. Ataxia-telangiectasia - a historical review and a proposal for a new designation: ATM syndrome. J Neurol Sci. 2015 Aug 15;355(1–2):3–6.
   PubMed Web of Science ®Google Scholar
• Savitsky K, Bar-Shira A, Gilad S, et al. A single ataxia telangiectasia gene with a product similar to PI-3 kinase. Science. 1995 Jun 23;268(5218):1749–1753.
   PubMed Web of Science ®Google Scholar
• Pietrucha B, Heropolitanska-Pliszka E, Gatti RA, et al. Ataxia-telangiectasia: guidelines for diagnosis and comprehensive care. Cent Eur J Immunol. 2007;32(4):234.
   Google Scholar
• Taylor A, Lam Z, Last J, et al. Ataxia telangiectasia: more variation at clinical and cellular levels. Clinical Genetics. 2014 Mar;87(3):199–208.
   PubMed Web of Science ®Google Scholar
• Ambrose M, Gatti RA. Pathogenesis of ataxia-telangiectasia: the next generation of ATM functions. Blood. 2013 May 16;121(20):4036–4045.
   PubMed Web of Science ®Google Scholar
• Chun HH, Gatti RA. Ataxia–telangiectasia, an evolving phenotype. DNA Repair. 2004;3(8):1187–1196.
   PubMed Web of Science ®Google Scholar
• Woods C, Taylor A. Ataxia telangiectasia in the British Isles: the clinical and laboratory features of 70 affected individuals. QJM. 1992;82(2):169–179.
   PubMed Web of Science ®Google Scholar
• Morio T, Takahashi N, Watanabe F, et al. Phenotypic variations between affected siblings with ataxia-telangiectasia: ataxia-telangiectasia in Japan. Int J Hematol. 2009;90(4):455–462.
   PubMed Web of Science ®Google Scholar
• Moin M, Aghamohammadi A, Kouhi A, et al. Ataxia-telangiectasia in Iran: clinical and laboratory features of 104 patients. Pediatr Neurol. 2007 Jul;37(1):21–28.
   PubMed Web of Science ®Google Scholar
• Kumar V, Alt FW, Oksenych V. Functional overlaps between XLF and the ATM-dependent DNA double strand break response. DNA Repair (Amst). 2014 Apr;16:11–22.
   PubMed Web of Science ®Google Scholar
• Oksenych V, Kumar V, Liu X, et al. Functional redundancy between the XLF and DNA-PKcs DNA repair factors in V (D) J recombination and nonhomologous DNA end joining. Proc Natl Acad Sci U S A. 2013;110(6):2234–2239.
   PubMed Web of Science ®Google Scholar
• Shabestari MS, Maljaei SH, Baradaran R, et al. Distribution of primary immunodeficiency diseases in the Turk ethnic group, living in the northwestern Iran. J Clin Immunol. 2007 Sep;27(5):510–516.
   PubMed Web of Science ®Google Scholar
• Telatar M, Teraoka S, Wang Z, et al. Ataxia-telangiectasia: identification and detection of founder-effect mutations in the ATM gene in ethnic populations. Am J Hum Genet. 1998 Jan;62(1):86–97.
   PubMed Web of Science ®Google Scholar
• Beaudin M, Dupré N. Autosomal recessive ataxias. Essentials of cerebellum and cerebellar disorders. Switzerland: Springer; 2016. p. 545–551.
   Google Scholar
• Mavrou A, Tsangaris GT, Roma E, et al. The ATM gene and ataxia telangiectasia. Anticancer Res. 2008 Jan-Feb;28(1B):401–405.
   PubMed Web of Science ®Google Scholar
• Cavaciuti E, Lauge A, Janin N, et al. Cancer risk according to type and location of ATM mutation in ataxia-telangiectasia families. Genes Chromosomes Cancer. 2005 Jan;42(1):1–9.
   PubMed Web of Science ®Google Scholar
• Lavin MF. Ataxia-telangiectasia: from a rare disorder to a paradigm for cell signalling and cancer. Nat Rev Mol Cell Biol. 2008 Oct;9(10):759–769.
   PubMed Web of Science ®Google Scholar
• Swift M, Morrell D, Massey RB, et al. Incidence of cancer in 161 families affected by ataxia-telangiectasia. N Engl J Med. 1991 Dec 26;325(26):1831–1836.
   PubMed Web of Science ®Google Scholar
• van Os NJ, Roeleveld N, Weemaes CM, et al. Health risks for ataxia-telangiectasia mutated heterozygotes: a systematic review, meta-analysis and evidence-based guideline. Clin Genet. 2016 Aug;90(2):105–117.
   PubMed Web of Science ®Google Scholar
• Taylor AM, Byrd PJ. Molecular pathology of ataxia telangiectasia. J Clin Pathol. 2005 Oct;58(10):1009–1015.
   PubMed Web of Science ®Google Scholar
• McGrath-Morrow SA, Gower WA, Rothblum-Oviatt C, et al. Evaluation and management of pulmonary disease in ataxia-telangiectasia. Pediatr Pulmonol. 2010 Sep;45(9):847–859.
   PubMed Web of Science ®Google Scholar
• Chessa L, Micheli R, Molinaro A. Focusing new ataxia telangiectasia therapeutic approaches. J Rare Dis Diagn Ther. 2016;2(2).
   Google Scholar
• Micol R, Ben Slama L, Suarez F, et al. Morbidity and mortality from ataxia-telangiectasia are associated with ATM genotype. J Allergy Clin Immunol. 2011 Aug;128(2):382–9 e1.
   PubMed Web of Science ®Google Scholar
• Conley ME, Notarangelo LD, Etzioni A. Diagnostic criteria for primary immunodeficiencies. Representing PAGID (Pan-American Group for Immunodeficiency) and ESID (European Society for Immunodeficiencies). Clin Immunol. 1999 Dec;93(3):190–197.
   PubMed Web of Science ®Google Scholar
• Chun HH, Sun X, Nahas SA, et al. Improved diagnostic testing for ataxia-telangiectasia by immunoblotting of nuclear lysates for ATM protein expression. Mol Genet Metab. 2003 Dec;80(4):437–443.
   PubMed Web of Science ®Google Scholar
• Painter RB, Young BR. Radiosensitivity in ataxia-telangiectasia: a new explanation. Proc Natl Acad Sci U S A. 1980 Dec;77(12):7315–7317.
   PubMed Web of Science ®Google Scholar
• Leuzzi V, Elli R, Antonelli A, et al. Neurological and cytogenetic study in early-onset ataxia-telangiectasia patients. Eur J Pediatr. 1993 Jul;152(7):609–612.
   PubMed Web of Science ®Google Scholar
• Crawford TO. Ataxia telangiectasia. Semin Pediatr Neurol. 1998 Dec;5(4):287–294.
   PubMedGoogle Scholar
• Perlman SL, Boder Deceased E, Sedgewick RP, et al. Ataxia-telangiectasia. Handb Clin Neurol. 2012;103:307–332.
   PubMedGoogle Scholar
• Woods CG, Taylor AM. Ataxia telangiectasia in the British Isles: the clinical and laboratory features of 70 affected individuals. Q J Med. 1992 Feb;82(298):169–179.
   PubMedGoogle Scholar
• Anheim M, Monga B, Fleury M, et al. Ataxia with oculomotor apraxia type 2: clinical, biological and genotype/phenotype correlation study of a cohort of 90 patients. Brain. 2009 Oct;132(Pt 10):2688–2698.
   PubMed Web of Science ®Google Scholar
• Devgan SS, Sanal O, Doil C, et al. Homozygous deficiency of ubiquitin-ligase ring-finger protein RNF168 mimics the radiosensitivity syndrome of ataxia-telangiectasia. Cell Death Differ. 2011 Sep;18(9):1500–1506.
   PubMed Web of Science ®Google Scholar
• Schneider DT, Calaminus G, Gobel U. Diagnostic value of alpha 1-fetoprotein and beta-human chorionic gonadotropin in infancy and childhood. Pediatr Hematol Oncol. 2001 Jan-Feb;18(1):11–26.
   PubMed Web of Science ®Google Scholar
• Stray-Pedersen A, Borresen-Dale AL, Paus E, et al. Alpha fetoprotein is increasing with age in ataxia-telangiectasia. Eur J Paediatr Neurol. 2007 Nov;11(6):375–380.
   PubMed Web of Science ®Google Scholar
• Jung CG, Kim HJ, Kawaguchi M, et al. Homeotic factor ATBF1 induces the cell cycle arrest associated with neuronal differentiation. Development. 2005 Dec;132(23):5137–5145.
   PubMed Web of Science ®Google Scholar
• Sun X, Becker-Catania SG, Chun HH, et al. Early diagnosis of ataxia-telangiectasia using radiosensitivity testing. J Pediatr. 2002 Jun;140(6):724–731.
   PubMed Web of Science ®Google Scholar
• Bryant P, Gray L, Riches A, et al. Technical report. The G2 chromosomal radiosensitivity assay. Int J Radiat Biol. 2002;78(9):863–866.
   PubMed Web of Science ®Google Scholar
• Cavalieri S, Funaro A, Porcedda P, et al. ATM mutations in Italian families with ataxia telangiectasia include two distinct large genomic deletions. Hum Mutat. 2006 Oct;27(10):1061.
   PubMedGoogle Scholar
• Gatti R, Perlman S. Ataxia-Telangiectasia. 1999 Mar 19 [Updated 2016 Oct 27]. In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993–2017. Available from: https://www.ncbi.nlm.nih.gov/books/NBK26468/
   Google Scholar
• Stenson PD, Ball EV, Mort M, et al. Human gene mutation database (HGMD®): 2003 update. Human Mutation. 2003;21(6):577–581.
   PubMed Web of Science ®Google Scholar
• Ball LG, Xiao W. Molecular basis of ataxia telangiectasia and related diseases. Acta Pharmacol Sin. 2005 Aug;26(8):897–907.
   PubMed Web of Science ®Google Scholar
• Becker-Catania SG, Chen G, Hwang MJ, et al. Ataxia-telangiectasia: phenotype/genotype studies of ATM protein expression, mutations, and radiosensitivity. Mol Genet Metab. 2000 Jun;70(2):122–133.
   PubMed Web of Science ®Google Scholar
• Verhagen MM, Abdo WF, Willemsen MA, et al. Clinical spectrum of ataxia-telangiectasia in adulthood. Neurology. 2009 Aug 11;73(6):430–437.
   PubMed Web of Science ®Google Scholar
• Buzin CH, Gatti RA, Nguyen VQ, et al. Comprehensive scanning of the ATM gene with DOVAM-S. Hum Mutat. 2003 Feb;21(2):123–131.
   PubMed Web of Science ®Google Scholar
• Mitui M, Campbell C, Coutinho G, et al. Independent mutational events are rare in the ATM gene: haplotype prescreening enhances mutation detection rate. Hum Mutat. 2003 Jul;22(1):43–50.
   PubMed Web of Science ®Google Scholar
• Concannon P, Gatti RA. Diversity of ATM gene mutations detected in patients with ataxia-telangiectasia. Hum Mutat. 1997;10(2):100–107.
   PubMed Web of Science ®Google Scholar
• Porcedda P, Turinetto V, Orlando L, et al. Two-tier analysis of histone H2AX phosphorylation allows the identification of ataxia telangiectasia heterozygotes. Radiother Oncol. 2009 Jul;92(1):133–137.
   PubMed Web of Science ®Google Scholar
• Prodosmo A, De Amicis A, Nistico C, et al. p53 centrosomal localization diagnoses ataxia-telangiectasia homozygotes and heterozygotes. J Clin Invest. 2013 Mar 1;123(3):1335–1342.
   PubMed Web of Science ®Google Scholar
• Claes K, Depuydt J, Taylor AM, et al. Variant ataxia telangiectasia: clinical and molecular findings and evaluation of radiosensitive phenotypes in a patient and relatives. Neuromolecular Med. 2013 Sep;15(3):447–457.
   PubMed Web of Science ®Google Scholar
• Nahas SA, Butch AW, Du L, et al. Rapid flow cytometry–based structural maintenance of chromosomes 1 (SMC1) phosphorylation assay for identification of ataxia-telangiectasia homozygotes and heterozygotes. Clinical Chemistry. 2009;55(3):463–472.
   PubMed Web of Science ®Google Scholar
• Dizaji MZ, Rezaei N, Yaghmaie M, et al. Phospho-SMC1 in-cell ELISA based detection of ataxia telangiectasia. Int J Pediatrics-Mashhad. 2016 Dec;4(12):3957–3967.
   Web of Science ®Google Scholar
• Gatti RA, Berkel I, Boder E, et al. Localization of an ataxia-telangiectasia gene to chromosome 11q22–23. Nature. 1988 Dec 8;336(6199):577–580.
   PubMed Web of Science ®Google Scholar
• Gilad S, Chessa L, Khosravi R, et al. Genotype-phenotype relationships in ataxia-telangiectasia and variants. Am J Hum Genet. 1998 Mar;62(3):551–561.
   PubMed Web of Science ®Google Scholar
• Uziel T, Savitsky K, Platzer M, et al. Genomic organization of the ATM gene. Genomics. 1996 Apr 15;33(2):317–320.
   PubMed Web of Science ®Google Scholar
• Shiloh Y, Ziv Y. The ATM protein kinase: regulating the cellular response to genotoxic stress, and more. Nat Rev Mol Cell Biol. 2013 Apr;14(4):197–210.
   Web of Science ®Google Scholar
• Shiloh Y. ATM and related protein kinases: safeguarding genome integrity. Nat Rev Cancer. 2003;3(3):155–168.
   PubMed Web of Science ®Google Scholar
• Lempiainen H, Halazonetis TD. Emerging common themes in regulation of PIKKs and PI3Ks. Embo J. 2009 Oct 21;28(20):3067–3073.
   PubMed Web of Science ®Google Scholar
• Cremona CA, Behrens A. ATM signalling and cancer. Oncogene. 2014 Jun 26;33(26):3351–3360.
   PubMed Web of Science ®Google Scholar
• Awasthi P, Foiani M, Atm KA. ATR signaling at a glance. J Cell Sci. 2015 Dec 1;128(23):4255–4262.
   PubMed Web of Science ®Google Scholar
• Soulas-Sprauel P, Rivera-Munoz P, Malivert L, et al. V(D)J and immunoglobulin class switch recombinations: a paradigm to study the regulation of DNA end-joining. Oncogene. 2007 Dec 10;26(56):7780–7791.
   PubMed Web of Science ®Google Scholar
• Keeney S, Neale MJ. Initiation of meiotic recombination by formation of DNA double-strand breaks: mechanism and regulation. Biochem Soc Trans. 2006 Aug;34(Pt 4):523–525.
   PubMed Web of Science ®Google Scholar
• Malkova A, Haber JE. Mutations arising during repair of chromosome breaks. Annu Rev Genet. 2012;46:455–473.
   PubMed Web of Science ®Google Scholar
• Uziel T, Lerenthal Y, Moyal L, et al. Requirement of the MRN complex for ATM activation by DNA damage. The EMBO Journal. 2003;22(20):5612–5621.
   PubMed Web of Science ®Google Scholar
• Paull TT. Mechanisms of ATM activation. Annu Rev Biochem. 2015;84:711–738.
   PubMed Web of Science ®Google Scholar
• Lee J-H, Paull TT. Direct activation of the ATM protein kinase by the Mre11/Rad50/Nbs1 complex. Science. 2004;304(5667):93–96.
   PubMed Web of Science ®Google Scholar
• Hartlerode AJ, Morgan MJ, Wu Y, et al. Recruitment and activation of the ATM kinase in the absence of DNA-damage sensors. Nat Struct Mol Biol. 2015 Sep;22(9):736–743.
   PubMed Web of Science ®Google Scholar
• Murga M, Jaco I, Fan Y, et al. Global chromatin compaction limits the strength of the DNA damage response. J Cell Biol. 2007;178(7):1101–1108.
   PubMed Web of Science ®Google Scholar
• Udayakumar D, Horikoshi N, Mishra L, et al. Detecting ATM-dependent chromatin modification in DNA damage response. Methods Mol Biol. 2015;1288:317–336.
   PubMedGoogle Scholar
• Kozlov SV, Graham ME, Jakob B, et al. Autophosphorylation and ATM activation: additional sites add to the complexity. J Biol Chem. 2011;286(11):9107–9119.
   PubMed Web of Science ®Google Scholar
• Kozlov SV, Graham ME, Peng C, et al. Involvement of novel autophosphorylation sites in ATM activation. The EMBO Journal. 2006;25(15):3504–3514.
   PubMed Web of Science ®Google Scholar
• Weber AM, Ryan AJATM. ATR as therapeutic targets in cancer. Pharmacol Ther. 2015 May;149:124–138.
   PubMed Web of Science ®Google Scholar
• Wu J, Chen Y, Lu L-Y, et al. Chfr and RNF8 synergistically regulate ATM activation. Nat Struct Mol Biol. 2011;18(7):761–768.
   PubMed Web of Science ®Google Scholar
• Schmidt L, Wiedner M, Velimezi G, et al. ATMIN is required for the ATM-mediated signaling and recruitment of 53BP1 to DNA damage sites upon replication stress. DNA Repair (Amst). 2014;24:122–130.
   PubMed Web of Science ®Google Scholar
• Chung YM, Park SH, Tsai WB, et al. FOXO3 signalling links ATM to the p53 apoptotic pathway following DNA damage. Nat Commun. 2012;3:1000.
   PubMed Web of Science ®Google Scholar
• Doil C, Mailand N, Bekker-Jensen S, et al. RNF168 binds and amplifies ubiquitin conjugates on damaged chromosomes to allow accumulation of repair proteins. Cell. 2009 Feb 6;136(3):435–446.
   PubMed Web of Science ®Google Scholar
• Mailand N, Bekker-Jensen S, Faustrup H, et al. RNF8 ubiquitylates histones at DNA double-strand breaks and promotes assembly of repair proteins. Cell. 2007 Nov 30;131(5):887–900.
   PubMed Web of Science ®Google Scholar
• Shibata A, Jeggo PA. DNA double-strand break repair in a cellular context. Clin Oncol (R Coll Radiol). 2014 May;26(5):243–249.
   PubMed Web of Science ®Google Scholar
• Iyama T, Wilson DM 3rd. DNA repair mechanisms in dividing and non-dividing cells. DNA Repair (Amst). 2013 Aug;12(8):620–636.
   PubMed Web of Science ®Google Scholar
• Hiom K. Coping with DNA double strand breaks. DNA Repair (Amst). 2010 Dec 10;9(12):1256–1263.
   PubMed Web of Science ®Google Scholar
• Clouaire T, Legube G. DNA double strand break repair pathway choice: a chromatin based decision? Nucleus. 2015 Mar 4;6(2):107–113.
   PubMed Web of Science ®Google Scholar
• Heyer WD, Ehmsen KT, Liu J. Regulation of homologous recombination in eukaryotes. Annu Rev Genet. 2010;44:113–139.
   PubMed Web of Science ®Google Scholar
• Ceccaldi R, Rondinelli B, D’Andrea AD. Repair pathway choices and consequences at the double-strand break. Trends Cell Biol. 2016;26(1):52–64.
   PubMed Web of Science ®Google Scholar
• Lemaitre C, Grabarz A, Tsouroula K, et al. Nuclear position dictates DNA repair pathway choice. Genes Dev. 2014 Nov 15;28(22):2450–2463.
   PubMed Web of Science ®Google Scholar
• Cannan WJ, Pederson DS. Mechanisms and consequences of double-strand DNA break formation in chromatin. J Cell Physiol. 2016 Jan;231(1):3–14.
   PubMed Web of Science ®Google Scholar
• Zimmermann M, De Lange T. 53BP1: pro choice in DNA repair. Trends Cell Biol. 2014 Feb;24(2):108–117.
   PubMed Web of Science ®Google Scholar
• Escribano-Diaz C, Orthwein A, Fradet-Turcotte A, et al. A cell cycle-dependent regulatory circuit composed of 53BP1-RIF1 and BRCA1-CtIP controls DNA repair pathway choice. Mol Cell. 2013 Mar 7;49(5):872–883.
   PubMed Web of Science ®Google Scholar
• Symington LS, Gautier J. Double-strand break end resection and repair pathway choice. Annu Rev Genet. 2011;45:247–271.
   PubMed Web of Science ®Google Scholar
• Peterson SE, Li Y, Wu-Baer F, et al. Activation of DSB processing requires phosphorylation of CtIP by ATR. Mol Cell. 2013 Feb 21;49(4):657–667.
   PubMed Web of Science ®Google Scholar
• Wang H, Shi LZ, Wong CC, et al. The interaction of CtIP and Nbs1 connects CDK and ATM to regulate HR-mediated double-strand break repair. PLoS Genet. 2013;9(2):e1003277.
   PubMed Web of Science ®Google Scholar
• Kim ST, Lim DS, Canman CE, et al. Substrate specificities and identification of putative substrates of ATM kinase family members. J Biol Chem. 1999 Dec 31;274(53):37538–37543.
   PubMed Web of Science ®Google Scholar
• Li Z, Yu J, Zhang T, et al. rs189037, a functional variant in ATM gene promoter, is associated with idiopathic nonobstructive azoospermia. Fertil Steril. 2013 Dec;100(6):1536–41 e1.
   PubMed Web of Science ®Google Scholar
• McKinnon PJ. ATM and the molecular pathogenesis of ataxia telangiectasia. Annu Rev Pathol. 2012;7:303–321.
   PubMed Web of Science ®Google Scholar
• Bhoumik A, Takahashi S, Breitweiser W, et al. ATM-dependent phosphorylation of ATF2 is required for the DNA damage response. Mol Cell. 2005 May 27;18(5):577–587.
   PubMed Web of Science ®Google Scholar
• Kitagawa R, Bakkenist CJ, McKinnon PJ, et al. Phosphorylation of SMC1 is a critical downstream event in the ATM-NBS1-BRCA1 pathway. Genes Dev. 2004 Jun 15;18(12):1423–1438.
   PubMed Web of Science ®Google Scholar
• Difilippantonio S, Celeste A, Kruhlak MJ, et al. Distinct domains in Nbs1 regulate irradiation-induced checkpoints and apoptosis. J Exp Med. 2007 May 14;204(5):1003–1011.
   PubMed Web of Science ®Google Scholar
• Kato A, Komatsu K. RNF20-SNF2H pathway of chromatin relaxation in DNA double-strand break repair. Genes (Basel). 2015;6(3):592–606.
   PubMed Web of Science ®Google Scholar
• Ui A, Nagaura Y, Yasui A. Transcriptional elongation factor ENL phosphorylated by ATM recruits polycomb and switches off transcription for DSB repair. Mol Cell. 2015 May 7;58(3):468–482.
   PubMed Web of Science ®Google Scholar
• Shanbhag NM, Rafalska-Metcalf IU, Balane-Bolivar C, et al. ATM-dependent chromatin changes silence transcription in cis to DNA double-strand breaks. Cell. 2010 Jun 11;141(6):970–981.
   PubMed Web of Science ®Google Scholar
• Kakarougkas A, Ismail A, Chambers AL, et al. Requirement for PBAF in transcriptional repression and repair at DNA breaks in actively transcribed regions of chromatin. Mol Cell. 2014 Sep 4;55(5):723–732.
   PubMed Web of Science ®Google Scholar
• Stewart GS, Panier S, Townsend K, et al. The RIDDLE syndrome protein mediates a ubiquitin-dependent signaling cascade at sites of DNA damage. Cell. 2009 Feb 6;136(3):420–434.
   PubMed Web of Science ®Google Scholar
• Gottschling DE, Aparicio OM, Billington BL, et al. Position effect at S. cerevisiae telomeres: reversible repression of Pol II transcription. Cell. 1990 Nov 16;63(4):751–762.
   PubMed Web of Science ®Google Scholar
• Oikemus SR, McGinnis N, Queiroz-Machado J, et al. Drosophila atm/telomere fusion is required for telomeric localization of HP1 and telomere position effect. Genes Dev. 2004 Aug 1;18(15):1850–1861.
   PubMed Web of Science ®Google Scholar
• Metcalfe JA, Parkhill J, Campbell L, et al. Accelerated telomere shortening in ataxia telangiectasia. Nat Genet. 1996;13(3):350–353.
   PubMed Web of Science ®Google Scholar
• Kong CM, Lee XW, Wang X. Telomere shortening in human diseases. Febs J. 2013 Jul;280(14):3180–3193.
   PubMed Web of Science ®Google Scholar
• Boohaker RJ, Xu B. The versatile functions of ATM kinase. Biomed J. 2014 Jan-Feb;37(1):3–9.
   PubMedGoogle Scholar
• Helgason H, Rafnar T, Olafsdottir HS, et al. Loss-of-function variants in ATM confer risk of gastric cancer. Nat Genet. 2015 Aug;47(8):906–910.
   PubMed Web of Science ®Google Scholar
• Roberts NJ, Jiao Y, Yu J, et al. ATM mutations in patients with hereditary pancreatic cancer. Cancer Discov. 2012 Jan;2(1):41–46.
   PubMed Web of Science ®Google Scholar
• Stagni V, Oropallo V, Fianco G, et al. Tug of war between survival and death: exploring ATM function in cancer. Int J Mol Sci. 2014;15(4):5388–5409.
   PubMed Web of Science ®Google Scholar
• Guarini A, Marinelli M, Tavolaro S, et al. ATM gene alterations in chronic lymphocytic leukemia patients induce a distinct gene expression profile and predict disease progression. Haematologica. 2012 Jan;97(1):47–55.
   PubMed Web of Science ®Google Scholar
• Stilgenbauer S, Schaffner C, Litterst A, et al. Biallelic mutations in the ATM gene in T-prolymphocytic leukemia. Nat Med. 1997 Oct;3(10):1155–1159.
   PubMed Web of Science ®Google Scholar
• Gronbaek K, Worm J, Ralfkiaer E, et al. ATM mutations are associated with inactivation of the ARF-TP53 tumor suppressor pathway in diffuse large B-cell lymphoma. Blood. 2002 Aug 15;100(4):1430–1437.
   PubMed Web of Science ®Google Scholar
• Wang L, Lawrence MS, Wan Y, et al. SF3B1 and other novel cancer genes in chronic lymphocytic leukemia. N Engl J Med. 2011 Dec 29;365(26):2497–2506.
   PubMed Web of Science ®Google Scholar
• Bea S, Valdes-Mas R, Navarro A, et al. Landscape of somatic mutations and clonal evolution in mantle cell lymphoma. Proc Natl Acad Sci U S A. 2013 Nov 5;110(45):18250–18255.
   PubMed Web of Science ®Google Scholar
• Isaian A, Bogdanova NV, Houshmand M, et al. BAK, BAX, and NBK/BIK proapoptotic gene alterations in Iranian patients with ataxia telangiectasia. J Clin Immunol. 2010 Jan;30(1):132–137.
   PubMed Web of Science ®Google Scholar
• Jackson SP, Bartek J. The DNA-damage response in human biology and disease. Nature. 2009 Oct 22;461(7267):1071–1078.
   PubMed Web of Science ®Google Scholar
• Suarez F, Mahlaoui N, Canioni D, et al. Incidence, presentation, and prognosis of malignancies in ataxia-telangiectasia: a report from the French national registry of primary immune deficiencies. J Clin Oncol. 2015 Jan 10;33(2):202–208.
   PubMed Web of Science ®Google Scholar
• Reiman A, Srinivasan V, Barone G, et al. Lymphoid tumours and breast cancer in ataxia telangiectasia; substantial protective effect of residual ATM kinase activity against childhood tumours. Br J Cancer. 2011 Aug 9;105(4):586–591.
   PubMed Web of Science ®Google Scholar
• Aurias A, Dutrillaux B, Buriot D, et al. High frequencies of inversions and translocations of chromosomes 7 and 14 in ataxia telangiectasia. Mutat Res. 1980 Feb;69(2):369–374.
   PubMed Web of Science ®Google Scholar
• Kojis TL, Gatti RA, Sparkes RS. The cytogenetics of ataxia telangiectasia. Cancer Genet Cytogenet. 1991 Oct 15;56(2):143–156.
   PubMedGoogle Scholar
• Aurias A. Cytogenetic analysis of 21 cases of ataxia telangiectasia. J Genet Hum. 1981;29(3):235.
   PubMedGoogle Scholar
• McKinnon PJ. ATM and ataxia telangiectasia. EMBO Rep. 2004 Aug;5(8):772–776.
   PubMed Web of Science ®Google Scholar
• Zha S, Bassing CH, Sanda T, et al. ATM-deficient thymic lymphoma is associated with aberrant tcrd rearrangement and gene amplification. J Exp Med. 2010 Jul 05;207(7):1369–1380.
   PubMed Web of Science ®Google Scholar
• Isoda T, Takagi M, Piao J, et al. Process for immune defect and chromosomal translocation during early thymocyte development lacking ATM. Blood. 2012 Jul 26;120(4):789–799.
   PubMed Web of Science ®Google Scholar
• Jiang W, Lee BJ, Li C, et al. Aberrant TCRdelta rearrangement underlies the T-cell lymphocytopenia and t(12;14) translocation associated with ATM deficiency. Blood. 2015 Apr 23;125(17):2665–2668.
   PubMed Web of Science ®Google Scholar
• Shigeta T, Takagi M, Delia D, et al. Defective control of apoptosis and mitotic spindle checkpoint in heterozygous carriers of ATM mutations. Cancer Research. 1999;59(11):2602–2607.
   PubMed Web of Science ®Google Scholar
• Takagi M, Delia D, Chessa L, et al. Defective control of apoptosis, radiosensitivity, and spindle checkpoint in ataxia telangiectasia. Cancer Research. 1998;58(21):4923–4929.
   PubMed Web of Science ®Google Scholar
• Banin S, Moyal L, Shieh S-Y, et al. Enhanced phosphorylation of p53 by ATM in response to DNA damage. Science. 1998;281(5383):1674–1677.
   PubMed Web of Science ®Google Scholar
• Hirao A, Kong -Y-Y, Matsuoka S, et al. DNA damage-induced activation of p53 by the checkpoint kinase Chk2. Science. 2000;287(5459):1824–1827.
   PubMed Web of Science ®Google Scholar
• Li M, Fang X, Baker DJ, et al. The ATM–p53 pathway suppresses aneuploidy-induced tumorigenesis. Proc Natl Acad Sci U S A. 2010;107(32):14188–14193.
   PubMed Web of Science ®Google Scholar
• Yang C, Wang H, Xu Y, et al. The kinetochore protein Bub1 participates in the DNA damage response. DNA Repair (Amst). 2012 Feb 1;11(2):185–191.
   PubMed Web of Science ®Google Scholar
• Stagni V, Mingardi M, Santini S, et al. ATM kinase activity modulates cFLIP protein levels: potential interplay between DNA damage signalling and TRAIL-induced apoptosis. Carcinogenesis. 2010 Nov;31(11):1956–1963.
   PubMed Web of Science ®Google Scholar
• Stagni V, Di Bari MG, Cursi S, et al. ATM kinase activity modulates Fas sensitivity through the regulation of FLIP in lymphoid cells. Blood. 2008 Jan 15;111(2):829–837.
   PubMed Web of Science ®Google Scholar
• Yamamoto K, Lee BJ, Li C, et al. Early B-cell-specific inactivation of ATM synergizes with ectopic CyclinD1 expression to promote pre-germinal center B-cell lymphomas in mice. Leukemia. 2015 Jun;29(6):1414–1424.
   PubMed Web of Science ®Google Scholar
• Kamsler A, Daily D, Hochman A, et al. Increased oxidative stress in ataxia telangiectasia evidenced by alterations in redox state of brains from Atm-deficient mice. Cancer Res. 2001;61(5):1849–1854.
   PubMed Web of Science ®Google Scholar
• Barlow C, Dennery PA, Shigenaga MK, et al. Loss of the ataxia-telangiectasia gene product causes oxidative damage in target organs. Proc Natl Acad Sci U S A. 1999 Aug 17;96(17):9915–9919.
   PubMed Web of Science ®Google Scholar
• Reliene R, Schiestl RH. Experimental antioxidant therapy in ataxia telangiectasia. Clin Med Oncol. 2008;2:431–436.
   PubMedGoogle Scholar
• Chen BP, Li M, Asaithamby A. New insights into the roles of ATM and DNA-PKcs in the cellular response to oxidative stress. Cancer Lett. 2012 Dec 31;327(1–2):103–110.
   PubMed Web of Science ®Google Scholar
• D’Souza AD, Parish IA, Krause DS, et al. Reducing mitochondrial ROS improves disease-related pathology in a mouse model of ataxia-telangiectasia. Mol Ther. 2013 Jan;21(1):42–48.
   PubMed Web of Science ®Google Scholar
• Ito K, Hirao A, Arai F, et al. Regulation of oxidative stress by ATM is required for self-renewal of haematopoietic stem cells. Nature. 2004 Oct 21;431(7011):997–1002.
   PubMed Web of Science ®Google Scholar
• Liang R, Ghaffari S. Stem cells, redox signaling, and stem cell aging. Antioxid Redox Signal. 2014 Apr 20;20(12):1902–1916.
   PubMed Web of Science ®Google Scholar
• Bencokova Z, Kaufmann MR, Pires IM, et al. ATM activation and signaling under hypoxic conditions. Mol Cell Biol. 2009 Jan;29(2):526–537.
   PubMed Web of Science ®Google Scholar
• Cam H, Easton JB, High A, et al. mTORC1 signaling under hypoxic conditions is controlled by ATM-dependent phosphorylation of HIF-1alpha. Mol Cell. 2010 Nov 24;40(4):509–520.
   PubMed Web of Science ®Google Scholar
• Alexander A, Cai SL, Kim J, et al. ATM signals to TSC2 in the cytoplasm to regulate mTORC1 in response to ROS. Proc Natl Acad Sci U S A. 2010 Mar 2;107(9):4153–4158.
   PubMed Web of Science ®Google Scholar
• Ousset M, Bouquet F, Fallone F, et al. Loss of ATM positively regulates the expression of hypoxia inducible factor 1 (HIF-1) through oxidative stress: role in the physiopathology of the disease. Cell Cycle. 2010 Jul 15;9(14):2814–2822.
   PubMed Web of Science ®Google Scholar
• Cuatrecasas M, Santamaria G, Velasco M, et al. ATM gene expression is associated with differentiation and angiogenesis in infiltrating breast carcinomas. Histol Histopathol. 2006 Feb;21(2):149–156.
   PubMed Web of Science ®Google Scholar
• Okuno Y, Nakamura-Ishizu A, Otsu K, et al. Pathological neoangiogenesis depends on oxidative stress regulation by ATM. Nat Med. 2012 Aug;18(8):1208–1216.
   PubMed Web of Science ®Google Scholar
• Noch E, Khalili K. Oncogenic viruses and tumor glucose metabolism: like kids in a candy store. Mol Cancer Ther. 2012 Jan;11(1):14–23.
   PubMed Web of Science ®Google Scholar
• Chen S, Sang N. Hypoxia-inducible factor-1: a critical player in the survival strategy of stressed cells. J Cell Biochem. 2016 Feb;117(2):267–278.
   PubMed Web of Science ®Google Scholar
• Choi M, Kipps T, Kurzrock R. ATM mutations in cancer: therapeutic implications. Mol Cancer Ther. 2016 Jul 13.
   Web of Science ®Google Scholar
• van Os NJ, Roeleveld N, Weemaes CM, et al. Health risks for ataxia-telangiectasia mutated heterozygotes: a systematic review, meta-analysis and evidence-based guideline. Clin Genet. 2016 Aug;90(2):105–117.
   PubMed Web of Science ®Google Scholar
• Goldgar DE, Healey S, Dowty JG, et al. Rare variants in the ATM gene and risk of breast cancer. Breast Cancer Res. 2011;13(4):R73.
   PubMed Web of Science ®Google Scholar
• Gatti RA, Tward A, Concannon P. Cancer risk in ATM heterozygotes: a model of phenotypic and mechanistic differences between missense and truncating mutations. Mol Genet Metab. 1999 Dec;68(4):419–423.
   PubMed Web of Science ®Google Scholar
• Tavtigian SV, Oefner PJ, Babikyan D, et al. Rare, evolutionarily unlikely missense substitutions in ATM confer increased risk of breast cancer. Am J Hum Genet. 2009 Oct;85(4):427–446.
   PubMed Web of Science ®Google Scholar
• Mangone FR, Miracca EC, Feilotter HE, et al. ATM gene mutations in sporadic breast cancer patients from Brazil. Springerplus. 2015;4:23.
   PubMed Web of Science ®Google Scholar
• Scott SP, Bendix R, Chen P, et al. Missense mutations but not allelic variants alter the function of ATM by dominant interference in patients with breast cancer. Proc Natl Acad Sci U S A. 2002 Jan 22;99(2):925–930.
   PubMed Web of Science ®Google Scholar
• Song L, Lin C, Wu Z, et al. miR-18a impairs DNA damage response through downregulation of ataxia telangiectasia mutated (ATM) kinase. PLoS One. 2011;6(9):e25454.
   PubMed Web of Science ®Google Scholar
• Ng WL, Yan D, Zhang X, et al. Over-expression of miR-100 is responsible for the low-expression of ATM in the human glioma cell line: M059J. DNA Repair (Amst). 2010 Nov 10;9(11):1170–1175.
   PubMed Web of Science ®Google Scholar
• Yan D, Ng WL, Zhang X, et al. Targeting DNA-PKcs and ATM with miR-101 sensitizes tumors to radiation. PLoS One. 2010;5(7):e11397.
   PubMed Web of Science ®Google Scholar
• Zhou Y, Wan G, Spizzo R, et al. miR-203 induces oxaliplatin resistance in colorectal cancer cells by negatively regulating ATM kinase. Mol Oncol. 2014 Feb;8(1):83–92.
   PubMed Web of Science ®Google Scholar
• Hu H, Du L, Nagabayashi G, et al. ATM is down-regulated by N-Myc-regulated microRNA-421. Proc Natl Acad Sci U S A. 2010 Jan 26;107(4):1506–1511.
   PubMed Web of Science ®Google Scholar
• Mansour WY, Bogdanova NV, Kasten-Pisula U, et al. Aberrant overexpression of miR-421 downregulates ATM and leads to a pronounced DSB repair defect and clinical hypersensitivity in SKX squamous cell carcinoma. Radiother Oncol. 2013 Jan;106(1):147–154.
   PubMed Web of Science ®Google Scholar
• Vo QN, Kim W-J, Cvitanovic L, et al. The ATM gene is a target for epigenetic silencing in locally advanced breast cancer. Oncogene. 2004 Dec 16;23(58):9432–9437.
   PubMed Web of Science ®Google Scholar
• Delmonico L, Moreira AD, Franco MF, et al. CDKN2A (p14/p16) and ATM promoter methylation in patients with impalpable breast lesions. Hum Pathol. 2015 Oct;46(10):1540–1547.
   PubMed Web of Science ®Google Scholar
• Brennan K, Garcia-Closas M, Orr N, et al. Intragenic ATM methylation in peripheral blood DNA as a biomarker of breast cancer risk. Cancer Res. 2012 May 1;72(9):2304–2313.
   PubMed Web of Science ®Google Scholar
• Mehdipour P, Karami F, Javan F, et al. Linking ATM promoter methylation to cell cycle protein expression in brain tumor patients: cellular molecular triangle correlation in ATM territory. Mol Neurobiol. 2015 Aug;52(1):293–302.
   PubMed Web of Science ®Google Scholar
• Kim WJ, Vo QN, Shrivastav M, et al. Aberrant methylation of the ATM promoter correlates with increased radiosensitivity in a human colorectal tumor cell line. Oncogene. 2002 May 30;21(24):3864–3871.
   PubMed Web of Science ®Google Scholar
• Roy K, Wang L, Makrigiorgos GM, et al. Methylation of the ATM promoter in glioma cells alters ionizing radiation sensitivity. Biochem Biophys Res Commun. 2006 Jun 9;344(3):821–826.
   PubMed Web of Science ®Google Scholar
• Cao X, Li M. A new pathway for senescence regulation. Genomics Proteomics Bioinformatics. 2015 Dec;13(6):333–335.
   Web of Science ®Google Scholar
• Bartkova J, Horejsi Z, Koed K, et al. DNA damage response as a candidate anti-cancer barrier in early human tumorigenesis. Nature. 2005 Apr 14;434(7035):864–870.
   PubMed Web of Science ®Google Scholar
• Bartkova J, Rezaei N, Liontos M, et al. Oncogene-induced senescence is part of the tumorigenesis barrier imposed by DNA damage checkpoints. Nature. 2006 Nov 30;444(7119):633–637.
   PubMed Web of Science ®Google Scholar
• Wallace MD, Southard TL, Schimenti KJ, et al. Role of DNA damage response pathways in preventing carcinogenesis caused by intrinsic replication stress. Oncogene. 2014 Jul 10;33(28):3688–3695.
   PubMed Web of Science ®Google Scholar
• Santos MA, Faryabi RB, Ergen AV, et al. DNA-damage-induced differentiation of leukaemic cells as an anti-cancer barrier. Nature. 2014 Oct 02;514(7520):107–111.
   PubMed Web of Science ®Google Scholar
• Fan C, Quan R, Feng X, et al. ATM activation is accompanied with earlier stages of prostate tumorigenesis. Biochim Biophys Acta. 2006 Oct;1763(10):1090–1097.
   PubMed Web of Science ®Google Scholar
• Aird KM, Worth AJ, Snyder NW, et al. ATM couples replication stress and metabolic reprogramming during cellular senescence. Cell Rep. 2015 May 12;11(6):893–901.
   PubMed Web of Science ®Google Scholar
• Kozlowski M, Ladurner AGATM. MacroH2A.1, and SASP: the checks and balances of cellular senescence. Mol Cell. 2015 Sep 3;59(5):713–715.
   PubMed Web of Science ®Google Scholar
• Ando K, Kernan JL, Liu PH, et al. PIDD death-domain phosphorylation by ATM controls prodeath versus prosurvival PIDDosome signaling. Mol Cell. 2012 Sep 14;47(5):681–693.
   PubMed Web of Science ®Google Scholar
• Wilson CH, Shalini S, Filipovska A, et al. Age-related proteostasis and metabolic alterations in caspase-2-deficient mice. Cell Death Dis. 2015 Jan 6.
   Web of Science ®Google Scholar
• Sun M, Guo X, Qian X, et al. Activation of the ATM-Snail pathway promotes breast cancer metastasis. J Mol Cell Biol. 2012 Oct;4(5):304–315.
   PubMed Web of Science ®Google Scholar
• Chen WT, Ebelt ND, Stracker TH, et al. ATM regulation of IL-8 links oxidative stress to cancer cell migration and invasion. Elife. 2015 June 1;4.
   Web of Science ®Google Scholar
• Boohaker RJ, Cui X, Stackhouse M, et al. ATM-mediated Snail Serine 100 phosphorylation regulates cellular radiosensitivity. Radiother Oncol. 2013 Sep;108(3):403–408.
   PubMed Web of Science ®Google Scholar
• Stracker TH, Roig I, Knobel PA, et al. The ATM signaling network in development and disease. Front Genet. 2013;4:37.
   PubMedGoogle Scholar
• Kraus M, Lev A, Simon AJ, et al. Disturbed B and T cell homeostasis and neogenesis in patients with ataxia telangiectasia. J Clin Immunol. 2014 Jul;34(5):561–572.
   PubMed Web of Science ®Google Scholar
• Ghiasy S, Parvaneh L, Azizi G, et al. The clinical significance of complete class switching defect in ataxia telangiectasia patients. Expert Rev Clin Immunol. 2017 May;13(5):499–505.
   PubMed Web of Science ®Google Scholar
• Reina-San-Martin B, Chen HT, Nussenzweig A, et al. ATM is required for efficient recombination between immunoglobulin switch regions. J Exp Med. 2004 Nov 1;200(9):1103–1110.
   PubMed Web of Science ®Google Scholar
• Lumsden JM, McCarty T, Petiniot LK, et al. Immunoglobulin class switch recombination is impaired in Atm-deficient mice. J Exp Med. 2004;200(9):1111–1121.
   PubMed Web of Science ®Google Scholar
• Callén E, Jankovic M, Difilippantonio S, et al. ATM prevents the persistence and propagation of chromosome breaks in lymphocytes. Cell. 2007;130(1):63–75.
   PubMed Web of Science ®Google Scholar
• Nussenzweig A, Nussenzweig MC. Origin of chromosomal translocations in lymphoid cancer. Cell. 2010;141(1):27–38.
   PubMed Web of Science ®Google Scholar
• Helmink BA, Sleckman BP. The response to and repair of RAG-mediated DNA double-strand breaks. Annu Rev Immunol. 2012;30:175–202.
   PubMed Web of Science ®Google Scholar
• Malu S, Malshetty V, Francis D, et al. Role of non-homologous end joining in V(D)J recombination. Immunol Res. 2012 Dec;54(1–3):233–246.
   PubMed Web of Science ®Google Scholar
• Alt FW, Zhang Y, Meng FL, et al. Mechanisms of programmed DNA lesions and genomic instability in the immune system. Cell. 2013 Jan 31;152(3):417–429.
   PubMed Web of Science ®Google Scholar
• Hammarstrom L. Primary immunodeficiencies screening: neonatal screening for T/B cell disorders - a triplex PCR method for quantitation of TRECs and KRECs in newborns. Clin Exp Immunol. 2014 Dec;178 Suppl 1:14–15.
   PubMed Web of Science ®Google Scholar
• Perkins EJ, Nair A, Cowley DO, et al. Sensing of intermediates in V (D) J recombination by ATM. Genes & Development. 2002;16(2):159–164.
   PubMed Web of Science ®Google Scholar
• Meek K, Xu Y, Bailie C, et al. The ATM kinase restrains joining of both VDJ signal and coding ends. J Immunol. 2016 Oct 15;197(8):3165–3174.
   PubMed Web of Science ®Google Scholar
• Neal JA, Xu Y, Abe M, et al. Restoration of ATM expression in DNA-PKcs-deficient cells inhibits signal end joining. J Immunol. 2016 Apr 1;196(7):3032–3042.
   PubMed Web of Science ®Google Scholar
• Bredemeyer AL, Sharma GG, Huang CY, et al. ATM stabilizes DNA double-strand-break complexes during V(D)J recombination. Nature. 2006 Jul 27;442(7101):466–470.
   PubMed Web of Science ®Google Scholar
• Barlow C, Hirotsune S, Paylor R, et al. Atm-deficient mice: a paradigm of ataxia telangiectasia. Cell. 1996 Jul 12;86(1):159–171.
   PubMed Web of Science ®Google Scholar
• Dujka M, Puebla-Osorio N, Tavana O, et al. ATM and p53 are essential in the cell-cycle containment of DNA breaks during V (D) J recombination in vivo. Oncogene. 2010;29(7):957–965.
   PubMed Web of Science ®Google Scholar
• Steinel NC, Lee BS, Tubbs AT, et al. The ataxia telangiectasia mutated kinase controls Igkappa allelic exclusion by inhibiting secondary Vkappa-to-Jkappa rearrangements. J Exp Med. 2013 Feb 11;210(2):233–239.
   PubMed Web of Science ®Google Scholar
• Fisher M, Bassing C. Pre-B cells suppress RAG expression in response to DNA double-strand breaks (HEM1P. 225). J Immunol. 2015 May 1;194(1 Supplement):50.8–50.8.
   PubMed Web of Science ®Google Scholar
• Nowak-Wegrzyn A, Crawford TO, Winkelstein JA, et al. Immunodeficiency and infections in ataxia-telangiectasia. J Pediatr. 2004 Apr;144(4):505–511.
   PubMed Web of Science ®Google Scholar
• Stavnezer J, Guikema JE, Schrader CE. Mechanism and regulation of class switch recombination. Annu Rev Immunol. 2008;26:261–292.
   PubMed Web of Science ®Google Scholar
• Hwang JK, Alt FW, Yeap L-S. Related mechanisms of antibody somatic hypermutation and class switch recombination. Microbiol Spectr. 2015 Feb;3(1):MDNA3-0037-2014.
   PubMed Web of Science ®Google Scholar
• Stavnezer J, Schrader CE. IgH chain class switch recombination: mechanism and regulation. J Immunol. 2014 Dec 1;193(11):5370–5378.
   PubMed Web of Science ®Google Scholar
• Khair L, Guikema JEJ, Linehan EK, et al. ATM increases activation-induced cytidine deaminase activity at downstream S regions during class-switch recombination. J Immunol. 2014 May 15;192(10):4887–4896.
   PubMed Web of Science ®Google Scholar
• Bassing CH, Alt FW. H2AX may function as an anchor to hold broken chromosomal DNA ends in close proximity. Cell Cycle. 2004 Feb;3(2):149–153.
   PubMed Web of Science ®Google Scholar
• Franco S, Gostissa M, Zha S, et al. H2AX prevents DNA breaks from progressing to chromosome breaks and translocations. Mol Cell. 2006 Jan 20;21(2):201–214.
   PubMed Web of Science ®Google Scholar
• Gapud EJ, Sleckman BP. Unique and redundant functions of ATM and DNA-PKcs during V (D) J recombination. Cell Cycle. 2011;10(12):1928–1935.
   PubMed Web of Science ®Google Scholar
• Zha S, Jiang W, Fujiwara Y, et al. Ataxia telangiectasia-mutated protein and DNA-dependent protein kinase have complementary V (D) J recombination functions. Proc Natl Acad Sci U S A. 2011 Feb 1;108(5):2028–2033.
   PubMed Web of Science ®Google Scholar
• Zha S, Guo C, Boboila C, et al. ATM damage response and XLF repair factor are functionally redundant in joining DNA breaks. Nature. 2011 Jan 13;469(7329):250–254.
   PubMed Web of Science ®Google Scholar
• Pan Q, Petit-Frere C, Lahdesmaki A, et al. Alternative end joining during switch recombination in patients with ataxia-telangiectasia. Eur J Immunol. 2002 May;32(5):1300–1308.
   PubMed Web of Science ®Google Scholar
• Ito K, Hirao A, Arai F, et al. Reactive oxygen species act through p38 MAPK to limit the lifespan of hematopoietic stem cells. Nat Med. 2006 Apr;12(4):446–451.
   PubMed Web of Science ®Google Scholar
• Kaur J. A comprehensive review on metabolic syndrome. Cardiol Res Pract. 2014;2014:943162.
   PubMedGoogle Scholar
• Wu D, Yang H, Xiang W, et al. Heterozygous mutation of ataxia-telangiectasia mutated gene aggravates hypercholesterolemia in apoE-deficient mice. J Lipid Res. 2005 Jul;46(7):1380–1387.
   PubMed Web of Science ®Google Scholar
• Su Y, Swift M. Mortality rates among carriers of ataxia-telangiectasia mutant alleles. Ann Intern Med. 2000 Nov 21;133(10):770–778.
   PubMed Web of Science ®Google Scholar
• Schneider JG, Finck BN, Ren J, et al. ATM-dependent suppression of stress signaling reduces vascular disease in metabolic syndrome. Cell Metab. 2006 Nov;4(5):377–389.
   PubMed Web of Science ®Google Scholar
• Swift M, Chase C. Cancer and cardiac deaths in obligatory ataxia-telangiectasia heterozygotes. Lancet. 1983 May 7;1(8332):1049–1050.
   PubMed Web of Science ®Google Scholar
• Mathers CD, Boerma T, Ma Fat D. Global and regional causes of death. Br Med Bull. 2009;92:7–32.
   PubMed Web of Science ®Google Scholar
• Barnes PJ. Mechanisms of development of multimorbidity in the elderly. Eur Respir J. 2015 Mar;45(3):790–806.
   PubMed Web of Science ®Google Scholar
• Guleria A, Chandna S. ATM kinase: much more than a DNA damage responsive protein. DNA Repair (Amst). 2015 Mar;39:1–20.
   PubMed Web of Science ®Google Scholar
• Espach Y, Lochner A, Strijdom H, et al. ATM protein kinase signaling, type 2 diabetes and cardiovascular disease. Cardiovasc Drugs Ther. 2015 Feb;29(1):51–58.
   PubMed Web of Science ®Google Scholar
• Gray K, Bennett M. Role of DNA damage in atherosclerosis–bystander or participant? Biochem Pharmacol. 2011 Oct 1;82(7):693–700.
   PubMed Web of Science ®Google Scholar
• Watters DJ. Oxidative stress in ataxia telangiectasia. Redox Rep. 2003;8(1):23–29.
   PubMed Web of Science ®Google Scholar
• Ditch S, Paull TT. The ATM protein kinase and cellular redox signaling: beyond the DNA damage response. Trends Biochem Sci. 2012 Jan;37(1):15–22.
   PubMed Web of Science ®Google Scholar
• Valentin-Vega YA, Maclean KH, Tait-Mulder J, et al. Mitochondrial dysfunction in ataxia-telangiectasia. Blood. 2012 Feb 9;119(6):1490–1500.
   PubMed Web of Science ®Google Scholar
• Mercer JR, Yu E, Figg N, et al. The mitochondria-targeted antioxidant MitoQ decreases features of the metabolic syndrome in ATM+/-/ApoE-/- mice. Free Radic Biol Med. 2012 Mar 01;52(5):841–849.
   PubMed Web of Science ®Google Scholar
• Alexander A, Kim J, Walker CL. ATM engages the TSC2/mTORC1 signaling node to regulate autophagy. Autophagy. 2010 Jul;6(5):672–673.
   PubMed Web of Science ®Google Scholar
• Cosentino C, Grieco D, Costanzo V. ATM activates the pentose phosphate pathway promoting anti-oxidant defence and DNA repair. Embo J. 2011 Feb 02;30(3):546–555.
   PubMed Web of Science ®Google Scholar
• Lee JH, Guo Z, Myler LR, et al. Direct activation of ATM by resveratrol under oxidizing conditions. PLoS One. 2014 Jun;9(6):e97969.
   PubMed Web of Science ®Google Scholar
• Bitterman JL, Chung JH. Metabolic effects of resveratrol: addressing the controversies. Cell Mol Life Sci. 2015 Apr;72(8):1473–1488.
   PubMed Web of Science ®Google Scholar
• Macaulay VM, Salisbury AJ, Bohula EA, et al. Downregulation of the type 1 insulin-like growth factor receptor in mouse melanoma cells is associated with enhanced radiosensitivity and impaired activation of Atm kinase. Oncogene. 2001 Jul 05;20(30):4029–4040.
   PubMed Web of Science ®Google Scholar
• Ching JK, Luebbert SH, Collins R, et al. Ataxia telangiectasia mutated impacts insulin-like growth factor 1 signalling in skeletal muscle. Exp Physiol. 2013 Feb;98(2):526–535.
   PubMed Web of Science ®Google Scholar
• Le Guezennec X, Brichkina A, Huang YF, et al. Wip1-dependent regulation of autophagy, obesity, and atherosclerosis. Cell Metab. 2012 Jul 3;16(1):68–80.
   PubMed Web of Science ®Google Scholar
• McGrath-Morrow SA, Collaco JM, Crawford TO, et al. Elevated serum IL-8 levels in ataxia telangiectasia. J Pediatr. 2010 Apr;156(4):682–4.e1.
   PubMed Web of Science ®Google Scholar
• McGrath-Morrow SA, Collaco JM, Detrick B, et al. Serum interleukin-6 levels and pulmonary function in ataxia-telangiectasia. J Pediatr. 2016;171:256–61 e1.
   PubMed Web of Science ®Google Scholar
• Hartlova A, Erttmann SF, Raffi FA, et al. DNA damage primes the type I interferon system via the cytosolic DNA sensor STING to promote anti-microbial innate immunity. Immunity. 2015 Feb 17;42(2):332–343.
   PubMed Web of Science ®Google Scholar
• Yu Q, Katlinskaya YV, Carbone CJ, et al. DNA-damage-induced type I interferon promotes senescence and inhibits stem cell function. Cell Rep. 2015 May 05;11(5):785–797.
   PubMed Web of Science ®Google Scholar
• Rodier F, Coppe JP, Patil CK, et al. Persistent DNA damage signalling triggers senescence-associated inflammatory cytokine secretion. Nat Cell Biol. 2009 Aug;11(8):973–979.
   PubMed Web of Science ®Google Scholar
• Erttmann SF, Hartlova A, Sloniecka M, et al. Loss of the DNA damage repair kinase ATM impairs inflammasome-dependent anti-bacterial innate immunity. Immunity. 2016 Jul 19;45(1):106–118.
   PubMed Web of Science ®Google Scholar
• Kim J, Wong PK. Oxidative stress is linked to ERK1/2-p16 signaling-mediated growth defect in ATM-deficient astrocytes. J Biol Chem. 2009 May 22;284(21):14396–14404.
   PubMed Web of Science ®Google Scholar
• Quick KL, Dugan LL. Superoxide stress identifies neurons at risk in a model of ataxia-telangiectasia. Ann Neurol. 2001 May;49(5):627–635.
   PubMed Web of Science ®Google Scholar
• Yang DQ, Kastan MB. Participation of ATM in insulin signalling through phosphorylation of eIF-4E-binding protein 1. Nat Cell Biol. 2000 Dec;2(12):893–898.
   PubMed Web of Science ®Google Scholar
• Zhou K, Bellenguez C, Spencer CC, et al. Common variants near ATM are associated with glycemic response to metformin in type 2 diabetes. Nat Genet. 2011 Feb;43(2):117–120.
   PubMed Web of Science ®Google Scholar
• Birnbaum MJ, Shaw RJ. Genomics: drugs, diabetes and cancer. Nature. 2011 Feb 17;470(7334):338–339.
   PubMed Web of Science ®Google Scholar
• Takagi M, Uno H, Nishi R, et al. ATM regulates adipocyte differentiation and contributes to glucose homeostasis. Cell Rep. 2015 Feb 17;10(6):957–967.
   Web of Science ®Google Scholar
• Exley AR, Buckenham S, Hodges E, et al. Premature ageing of the immune system underlies immunodeficiency in ataxia telangiectasia. Clin Immunol. 2011 Jul;140(1):26–36.
   PubMed Web of Science ®Google Scholar
• Shiloh Y, Lederman HM. Ataxia-telangiectasia (A-T): an emerging dimension of premature ageing. Ageing Res Rev. 2017 Jan;33:76–88.
   PubMed Web of Science ®Google Scholar
• Reliene R, Schiestl RH. Antioxidants suppress lymphoma and increase longevity in Atm-deficient mice. J Nutr. 2007 Jan;137(1 Suppl):229S–232S.
   PubMed Web of Science ®Google Scholar
• Lavin MF. The appropriateness of the mouse model for ataxia-telangiectasia: neurological defects but no neurodegeneration. DNA Repair (Amst). 2013 Aug;12(8):612–619.
   PubMed Web of Science ®Google Scholar
• Quek H, Luff J, Cheung K, et al. A rat model of ataxia-telangiectasia: evidence for a neurodegenerative phenotype. Hum Mol Genet. 2016 Dec 22.
   Web of Science ®Google Scholar
• Biton S, Barzilai A, Shiloh Y. The neurological phenotype of ataxia-telangiectasia: solving a persistent puzzle. DNA Repair (Amst). 2008 Jul 1;7(7):1028–1038.
   PubMed Web of Science ®Google Scholar
• Sahama I, Sinclair K, Pannek K, et al. Radiological imaging in ataxia telangiectasia: a review. Cerebellum. 2014 Aug;13(4):521–530.
   PubMed Web of Science ®Google Scholar
• Volkow ND, Tomasi D, Wang GJ, et al. Brain glucose metabolism in adults with ataxia-telangiectasia and their asymptomatic relatives. Brain. 2014 Jun;137(Pt 6):1753–1761.
   PubMed Web of Science ®Google Scholar
• Reynolds JJ, Stewart GS. A nervous predisposition to unrepaired DNA double strand breaks. DNA Repair (Amst). 2013 Aug;12(8):588–599.
   PubMed Web of Science ®Google Scholar
• Herrup K, Li J, Chen J. The role of ATM and DNA damage in neurons: upstream and downstream connections. DNA Repair (Amst). 2013 Aug;12(8):600–604.
   PubMed Web of Science ®Google Scholar
• Smith E, Dejsuphong D, Balestrini A, et al. An ATM- and ATR-dependent checkpoint inactivates spindle assembly by targeting CEP63. Nat Cell Biol. 2009 Mar;11(3):278–285.
   PubMed Web of Science ®Google Scholar
• Kumar A, Rajendran V, Sethumadhavan R, et al. CEP proteins: the knights of centrosome dynasty. Protoplasma. 2013 Oct;250(5):965–983.
   PubMed Web of Science ®Google Scholar
• Taylor A, Groom A, Byrd P. Ataxia-telangiectasia-like disorder (ATLD)—its clinical presentation and molecular basis. DNA Repair (Amst). 2004 Aug-Sep;3(8–9):1219–1225.
   PubMed Web of Science ®Google Scholar
• Digweed M, Sperling K. Nijmegen breakage syndrome: clinical manifestation of defective response to DNA double-strand breaks. DNA Repair (Amst). 2004 Aug-Sep;3(8–9):1207–1217.
   PubMed Web of Science ®Google Scholar
• Madabhushi R, Pan L, Tsai LH. DNA damage and its links to neurodegeneration. Neuron. 2014 Jul 16;83(2):266–282.
   PubMed Web of Science ®Google Scholar
• Yang Y, Hui CW, Li J, et al. The interaction of the Atm genotype with inflammation and oxidative stress. PLoS One. 2014 Jan 20;9(1):e85863.
   PubMed Web of Science ®Google Scholar
• Chen P, Peng C, Luff J, et al. Oxidative stress is responsible for deficient survival and dendritogenesis in Purkinje neurons from ataxia-telangiectasia mutated mutant mice. J Neuroscience. 2003 Dec 10;23(36):11453–11460.
   PubMed Web of Science ®Google Scholar
• Campbell A, Krupp B, Bushman J, et al. A novel mouse model for ataxia-telangiectasia with a N-terminal mutation displays a behavioral defect and a low incidence of lymphoma but no increased oxidative burden. Hum Mol Genet. 2015 Nov 15;24(22):6331–6349.
   PubMed Web of Science ®Google Scholar
• Nissenkorn A, Levi YB, Vilozni D, et al. Neurologic presentation in children with ataxia-telangiectasia: is small head circumference a hallmark of the disease?. J Pediatr. 2011 Sep;159(3):466–471 e1.
   PubMed Web of Science ®Google Scholar
• Guo Z, Kozlov S, Lavin MF, et al. ATM activation by oxidative stress. Science. 2010 Oct 22;330(6003):517–521.
   PubMed Web of Science ®Google Scholar
• Uttara B, Singh AV, Zamboni P, et al. Oxidative stress and neurodegenerative diseases: a review of upstream and downstream antioxidant therapeutic options. Curr Neuropharmacol. 2009 Mar;7(1):65–74.
   PubMed Web of Science ®Google Scholar
• Carlessi L, Fusar Poli E, Bechi G, et al. Functional and molecular defects of hiPSC-derived neurons from patients with ATM deficiency. Cell Death Dis. 2014 Jul;17(5):e1342.
   Web of Science ®Google Scholar
• Alagoz M, Chiang SC, Sharma A, et al. ATM deficiency results in accumulation of DNA-topoisomerase I covalent intermediates in neural cells. PLoS One. 2013 Apr 23;8(4):e58239.
   PubMedGoogle Scholar
• Weyemi U, Redon CE, Aziz T, et al. NADPH oxidase 4 is a critical mediator in ataxia telangiectasia disease. P Natl Acad Sci USA. 2015 Feb 17;112(7):2121–2126.
   PubMed Web of Science ®Google Scholar
• Chessa L. Current and future therapeutic strategies to treat ataxia telangiectasia. Expert Opinion on Orphan Drugs. 2014 Nov-Dec;2(9):877–887.
   Web of Science ®Google Scholar
• Anichini C, Lotti F, Longini M, et al. Antioxidant strategies in genetic syndromes with high neoplastic risk in infant age. Tumori. 2014 Nov-Dec;100(6):590–599.
   PubMed Web of Science ®Google Scholar
• Dobbin MM, Madabhushi R, Pan L, et al. SIRT1 collaborates with ATM and HDAC1 to maintain genomic stability in neurons. Nat Neurosci. 2013 Aug;16(8):1008–1015.
   PubMed Web of Science ®Google Scholar
• Li J, Herrup K. Alterations in epigenetic systems in AT neurodegeneration. Biohelikon Biol. 2013;1:1–2.
   Google Scholar
• Li J, Chen J, Ricupero CL, et al. Nuclear accumulation of HDAC4 in ATM deficiency promotes neurodegeneration in ataxia telangiectasia. Nat Med. 2012 May;18(5):783–790.
   PubMed Web of Science ®Google Scholar
• Chan SF, Sances S, Brill LM, et al. ATM-dependent phosphorylation of MEF2D promotes neuronal survival after DNA damage. J Neurosci. 2014 Mar 26;34(13):4640–4653.
   PubMed Web of Science ®Google Scholar
• Li J, Hart RP, Mallimo EM, et al. EZH2-mediated H3K27 trimethylation mediates neurodegeneration in ataxia-telangiectasia. Nat Neurosci. 2013 Dec;16(12):1745–1753.
   PubMed Web of Science ®Google Scholar
• Li J, Jiang D. The role of epigenomics in the neurodegeneration of ataxia-telangiectasia. Epigenomics. 2015;7(2):137–141.
   PubMed Web of Science ®Google Scholar
• Spilsbury A, Miwa S, Attems J, et al. The role of telomerase protein TERT in Alzheimer’s disease and in tau-related pathology in vitro. J Neurosci. 2015 Jan 28;35(4):1659–1674.
   PubMed Web of Science ®Google Scholar
• Weng NP, Levine BL, June CH, et al. Regulated expression of telomerase activity in human T lymphocyte development and activation. J Exp Med. 1996 Jun 1;183(6):2471–2479.
   PubMed Web of Science ®Google Scholar
• Eitan E, Hutchison ER, Mattson MP. Telomere shortening in neurological disorders: an abundance of unanswered questions. Trends Neurosci. 2014 May;37(5):256–263.
   PubMed Web of Science ®Google Scholar
• Suberbielle E, Sanchez PE, Kravitz AV, et al. Physiologic brain activity causes DNA double-strand breaks in neurons, with exacerbation by amyloid-[beta]. Nat Neurosci. 2013;16(5):613–621.
   PubMed Web of Science ®Google Scholar
• Atm: SY. Expanding roles as a chief guardian of genome stability. Exp Cell Res. 2014 Nov 15;329(1):154–161.
   PubMed Web of Science ®Google Scholar
• Miyamoto S. Nuclear initiated NF-kappaB signaling: NEMO and ATM take center stage. Cell Res. 2011 Jan;21(1):116–130.
   PubMed Web of Science ®Google Scholar
• Shiloh Y, Tabor E, Becker Y. Colony-forming ability of ataxia-telangiectasia skin fibroblasts is an indicator of their early senescence and increased demand for growth factors. Exp Cell Res. 1982 Jul;140(1):191–199.
   PubMed Web of Science ®Google Scholar
• Kang HT, Park JT, Choi K, et al. Chemical screening identifies ATM as a target for alleviating senescence. Nat Chem Biol. 2017 Jun;13(6):616–623.
   PubMed Web of Science ®Google Scholar
• Quek H, Luff J, Cheung K, et al. Rats with a missense mutation in Atm display neuroinflammation and neurodegeneration subsequent to accumulation of cytosolic DNA following unrepaired DNA damage. J Leukoc Biol. 2017 Apr;101(4):927–947.
   PubMed Web of Science ®Google Scholar
• Quarantelli M, Giardino G, Prinster A, et al. Steroid treatment in ataxia-telangiectasia induces alterations of functional magnetic resonance imaging during prono-supination task. Eur J Paediatr Neurol. 2013 Mar;17(2):135–140.
   PubMed Web of Science ®Google Scholar
• Chessa L, Leuzzi V, Plebani A, et al. Intra-erythrocyte infusion of dexamethasone reduces neurological symptoms in ataxia teleangiectasia patients: results of a phase 2 trial. Orphanet J Rare Dis. 2014 Jan 9;09:5.
   Web of Science ®Google Scholar
• Sharma NK, Lebedeva M, Thomas T, et al. Intrinsic mitochondrial DNA repair defects in ataxia telangiectasia. DNA Repair (Amst). 2014;13:22–31.
   PubMed Web of Science ®Google Scholar
• Eaton JS, Lin ZP, Sartorelli AC, et al. Ataxia-telangiectasia mutated kinase regulates ribonucleotide reductase and mitochondrial homeostasis. J Clin Invest. 2007 Sep;117(9):2723–2734.
   PubMed Web of Science ®Google Scholar
• Li J, Han YR, Plummer MR, et al. Cytoplasmic ATM in neurons modulates synaptic function. Curr Biol. 2009 Dec 29;19(24):2091–2096.
   PubMed Web of Science ®Google Scholar
• Barlow C, Liyanage M, Moens PB, et al. Partial rescue of the prophase I defects of Atm-deficient mice by p53 and p21 null alleles. Nat Genet. 1997 Dec;17(4):462–466.
   PubMed Web of Science ®Google Scholar
• Nissenkorn A, Levy-Shraga Y, Banet-Levi Y, et al. Endocrine abnormalities in ataxia telangiectasia: findings from a national cohort. Pediatr Res. 2016 Jun;79(6):889–894.
   PubMed Web of Science ®Google Scholar
• Ji G, Yan L, Liu W, et al. Polymorphisms in double-strand breaks repair genes are associated with impaired fertility in Chinese population. Reproduction. 2013 May;145(5):463–470.
   PubMed Web of Science ®Google Scholar
• Dawson AJ, Marles S, Tomiuk M, et al. Ataxia-telangiectasia with female fertility. Am J Med Genet A. 2015 Aug;167A(8):1937–1939.
   PubMed Web of Science ®Google Scholar
• Worth PF, Srinivasan V, Smith A, et al. Very mild presentation in adult with classical cellular phenotype of ataxia telangiectasia. Mov Disord. 2013 Apr;28(4):524–528.
   PubMed Web of Science ®Google Scholar