Atm

Summary

Gene Symbol: Atm
Description: ataxia telangiectasia mutated
Alias: AI256621, C030026E19Rik, serine-protein kinase ATM, A-T mutated homolog, ataxia telangiectasia gene mutated in human beings, ataxia telangiectasia mutated homolog
Species: mouse
Products:     Atm

Top Publications

  1. Ito K, Hirao A, Arai F, Matsuoka S, Takubo K, Hamaguchi I, et al. Regulation of oxidative stress by ATM is required for self-renewal of haematopoietic stem cells. Nature. 2004;431:997-1002 pubmed
    The 'ataxia telangiectasia mutated' (Atm) gene maintains genomic stability by activating a key cell-cycle checkpoint in response to DNA damage, telomeric instability or oxidative stress...
  2. Zha S, Bassing C, Sanda T, Brush J, Patel H, Goff P, et al. ATM-deficient thymic lymphoma is associated with aberrant tcrd rearrangement and gene amplification. J Exp Med. 2010;207:1369-80 pubmed publisher
    Ataxia telangiectasia mutated (ATM) deficiency predisposes humans and mice to T lineage lymphomas with recurrent chromosome 14 translocations involving the T cell receptor alpha/delta (Tcra/d) locus...
  3. Kim J, Wong P. Oxidative stress is linked to ERK1/2-p16 signaling-mediated growth defect in ATM-deficient astrocytes. J Biol Chem. 2009;284:14396-404 pubmed publisher
    The gene that encodes the ATM protein kinase is mutated in ataxia-telangiectasia (A-T). One of the prominent features of A-T is progressive neurodegeneration...
  4. Stracker T, Morales M, Couto S, Hussein H, Petrini J. The carboxy terminus of NBS1 is required for induction of apoptosis by the MRE11 complex. Nature. 2007;447:218-21 pubmed
    The MRE11 complex (MRE11, RAD50 and NBS1) and the ataxia-telangiectasia mutated (ATM) kinase function in the same DNA damage response pathway to effect cell cycle checkpoint activation and apoptosis...
  5. Ito K, Takubo K, Arai F, Satoh H, Matsuoka S, Ohmura M, et al. Regulation of reactive oxygen species by Atm is essential for proper response to DNA double-strand breaks in lymphocytes. J Immunol. 2007;178:103-10 pubmed
    The ataxia telangiectasia-mutated (ATM) gene plays a pivotal role in the maintenance of genomic stability...
  6. Gladdy R, Nutter L, Kunath T, Danska J, Guidos C. p53-Independent apoptosis disrupts early organogenesis in embryos lacking both ataxia-telangiectasia mutated and Prkdc. Mol Cancer Res. 2006;4:311-8 pubmed
    The ataxia-telangiectasia mutated (ATM) protein and the nonhomologous end-joining (NHEJ) pathway play crucial roles in sensing and repairing DNA double-strand breaks in postnatal cells...
  7. FOSTER C, Singh M, Subramanian V, Singh K. Ataxia telangiectasia mutated kinase plays a protective role in ?-adrenergic receptor-stimulated cardiac myocyte apoptosis and myocardial remodeling. Mol Cell Biochem. 2011;353:13-22 pubmed publisher
    ..genes affected by ?-AR stimulation, and examined first time the role of ataxia telangiectasia mutated kinase (ATM) in cardiac myocyte apoptosis and myocardial remodeling following ?-AR stimulation...
  8. Watters D, Kedar P, Spring K, Bjorkman J, Chen P, Gatei M, et al. Localization of a portion of extranuclear ATM to peroxisomes. J Biol Chem. 1999;274:34277-82 pubmed
    The gene mutated in the human genetic disorder ataxia-telangiectasia codes for a protein, ATM, the known functions of which include response to DNA damage, cell cycle control, and meiotic recombination...
  9. Rybanska Spaeder I, Reynolds T, Chou J, Prakash M, Jefferson T, Huso D, et al. 53BP1 is limiting for NHEJ repair in ATM-deficient model systems that are subjected to oncogenic stress or radiation. Mol Cancer Res. 2013;11:1223-34 pubmed publisher
    The DNA damage response (DDR) factors ataxia telangiectasia mutated (ATM) and p53 binding protein 1 (53BP1) function as tumor suppressors in humans and mice, but the significance of their mutual interaction to the suppression of ..

More Information

Publications92

  1. Bennardo N, Stark J. ATM limits incorrect end utilization during non-homologous end joining of multiple chromosome breaks. PLoS Genet. 2010;6:e1001194 pubmed publisher
    ..We tested whether the ATM kinase limits chromosome rearrangements via suppressing incorrect end utilization during EJ repair of multiple DSBs...
  2. Williams B, Mirzoeva O, Morgan W, Lin J, Dunnick W, Petrini J. A murine model of Nijmegen breakage syndrome. Curr Biol. 2002;12:648-53 pubmed
    ..Several lines of evidence indicate that the ataxia-telangiectasia mutated (ATM) kinase and the Mre11 complex functionally interact...
  3. Pusapati R, Rounbehler R, Hong S, Powers J, Yan M, Kiguchi K, et al. ATM promotes apoptosis and suppresses tumorigenesis in response to Myc. Proc Natl Acad Sci U S A. 2006;103:1446-51 pubmed
    ..we demonstrate that p53 induction in response to Myc overexpression requires the ataxia-telangiectasia mutated (ATM) kinase, a major regulator of the cellular response to DNA double-strand breaks...
  4. WONG K, Maser R, Bachoo R, Menon J, Carrasco D, Gu Y, et al. Telomere dysfunction and Atm deficiency compromises organ homeostasis and accelerates ageing. Nature. 2003;421:643-8 pubmed
    Ataxia-telangiectasia (A-T) results from the loss of ataxia-telangiectasia mutated (Atm) function and is characterized by accelerated telomere loss, genomic instability, progressive neurological degeneration, premature ageing and ..
  5. Schneider J, Finck B, Ren J, Standley K, Takagi M, Maclean K, et al. ATM-dependent suppression of stress signaling reduces vascular disease in metabolic syndrome. Cell Metab. 2006;4:377-89 pubmed
    ..Here, we show that deficiency of one or two alleles of ATM, the protein mutated in the cancer-prone disease ataxia telangiectasia, worsens features of the metabolic syndrome, ..
  6. Brown E, Baltimore D. ATR disruption leads to chromosomal fragmentation and early embryonic lethality. Genes Dev. 2000;14:397-402 pubmed
    ..These data show that ATR is essential for early embryonic development and must function in processes other than regulation of p53. ..
  7. Orsburn B, Escudero B, Prakash M, Gesheva S, Liu G, Huso D, et al. Differential requirement for H2AX and 53BP1 in organismal development and genome maintenance in the absence of poly(ADP)ribosyl polymerase 1. Mol Cell Biol. 2010;30:2341-52 pubmed publisher
    Combined deficiencies of poly(ADP)ribosyl polymerase 1 (PARP1) and ataxia telangiectasia mutated (ATM) result in synthetic lethality and, in the mouse, early embryonic death...
  8. Bowen T, Yakushiji H, Montagna C, Jain S, Ried T, Wynshaw Boris A. Atm heterozygosity cooperates with loss of Brca1 to increase the severity of mammary gland cancer and reduce ductal branching. Cancer Res. 2005;65:8736-46 pubmed
    The role of homozygous ataxia telangiectasia mutated (ATM) mutations in familial and sporadic forms of cancer is well established, but the contribution of ATM heterozygosity to mammary gland and other cancers has been controversial...
  9. Williamson C, Muzik H, Turhan A, Zamo A, O Connor M, Bebb D, et al. ATM deficiency sensitizes mantle cell lymphoma cells to poly(ADP-ribose) polymerase-1 inhibitors. Mol Cancer Ther. 2010;9:347-57 pubmed publisher
    ..The ataxia telangiectasia mutated (ATM) gene is altered in several human cancers including mantle cell lymphoma (MCL)...
  10. Li J, Han Y, Plummer M, Herrup K. Cytoplasmic ATM in neurons modulates synaptic function. Curr Biol. 2009;19:2091-6 pubmed publisher
    b>ATM is a PI 3-kinase involved in DNA double-strand break repair...
  11. Weizman N, Shiloh Y, Barzilai A. Contribution of the Atm protein to maintaining cellular homeostasis evidenced by continuous activation of the AP-1 pathway in Atm-deficient brains. J Biol Chem. 2003;278:6741-7 pubmed
    ..b>ATM is missing or inactivated in patients with ataxia-telangiectasia...
  12. Matei I, Gladdy R, Nutter L, Canty A, Guidos C, Danska J. ATM deficiency disrupts Tcra locus integrity and the maturation of CD4+CD8+ thymocytes. Blood. 2007;109:1887-96 pubmed
    Mutations in ATM (ataxia-telangiectasia mutated) cause ataxia-telangiectasia (AT), a disease characterized by neurodegeneration, sterility, immunodeficiency, and T-cell leukemia...
  13. Reimann M, Loddenkemper C, Rudolph C, Schildhauer I, Teichmann B, Stein H, et al. The Myc-evoked DNA damage response accounts for treatment resistance in primary lymphomas in vivo. Blood. 2007;110:2996-3004 pubmed
    ..In this study, we generated ataxia telangiectasia mutated (Atm)-proficient and -deficient B-cell lymphomas in Emu-myc transgenic mice to examine the role of DDR defects in ..
  14. Valentin Vega Y, Maclean K, Tait Mulder J, Milasta S, Steeves M, Dorsey F, et al. Mitochondrial dysfunction in ataxia-telangiectasia. Blood. 2012;119:1490-500 pubmed publisher
    Ataxia-telangiectasia mutated (ATM) plays a central role in DNA damage responses, and its loss leads to development of T-cell malignancies...
  15. Barchi M, Mahadevaiah S, Di Giacomo M, Baudat F, de Rooij D, Burgoyne P, et al. Surveillance of different recombination defects in mouse spermatocytes yields distinct responses despite elimination at an identical developmental stage. Mol Cell Biol. 2005;25:7203-15 pubmed
    ..b>Atm(-)(/)(-) spermatocytes show similarities to Dmc1(-)(/)(-) spermatocytes, suggesting that ATM promotes meiotic DSB ..
  16. Bredemeyer A, Sharma G, Huang C, Helmink B, Walker L, Khor K, et al. ATM stabilizes DNA double-strand-break complexes during V(D)J recombination. Nature. 2006;442:466-70 pubmed
    The ATM (ataxia-telangiectasia mutated) protein kinase mediates early cellular responses to DNA double-strand breaks (DSBs) generated during metabolic processes or by DNA-damaging agents...
  17. Chong M, Murray M, Gosink E, Russell H, Srinivasan A, Kapsetaki M, et al. Atm and Bax cooperate in ionizing radiation-induced apoptosis in the central nervous system. Proc Natl Acad Sci U S A. 2000;97:889-94 pubmed
    ..is a hereditary multisystemic disease resulting from mutations of ataxia telangiectasia, mutated (ATM) and is characterized by neurodegeneration, cancer, immune defects, and hypersensitivity to ionizing radiation...
  18. Pellegrini M, Celeste A, Difilippantonio S, Guo R, Wang W, Feigenbaum L, et al. Autophosphorylation at serine 1987 is dispensable for murine Atm activation in vivo. Nature. 2006;443:222-5 pubmed
    The ATM (ataxia telangiectasia mutated) protein kinase is activated under physiological and pathological conditions that induce DNA double-strand breaks (DSBs)...
  19. Daniel J, Pellegrini M, Lee J, Paull T, Feigenbaum L, Nussenzweig A. Multiple autophosphorylation sites are dispensable for murine ATM activation in vivo. J Cell Biol. 2008;183:777-83 pubmed publisher
    ..breaks are initiated through activation of the evolutionarily conserved ataxia telangiectasia mutated (ATM) kinase...
  20. Kitagawa R, Bakkenist C, McKinnon P, Kastan M. Phosphorylation of SMC1 is a critical downstream event in the ATM-NBS1-BRCA1 pathway. Genes Dev. 2004;18:1423-38 pubmed
    The ATM protein kinase is activated by intermolecular autophosphorylation in response to DNA damage and initiates cellular signaling pathways that facilitate cell survival and reduce chromosomal breakage...
  21. Soares H, Morgan J, McKinnon P. Atm expression patterns suggest a contribution from the peripheral nervous system to the phenotype of ataxia-telangiectasia. Neuroscience. 1998;86:1045-54 pubmed
    ..To investigate the neuropathology of ataxia-telangiectasia, we used in situ hybridization to map Atm (the gene mutated in ataxia-telangiectasia) expression during mouse development...
  22. Xu Y, Yang E, Brugarolas J, Jacks T, Baltimore D. Involvement of p53 and p21 in cellular defects and tumorigenesis in Atm-/- mice. Mol Cell Biol. 1998;18:4385-90 pubmed
    Disruption of the mouse Atm gene, whose human counterpart is consistently mutated in ataxia-telangiectasia (A-T) patients, creates an A-T mouse model exhibiting most of the A-T-related systematic and cellular defects...
  23. Callen E, Jankovic M, Difilippantonio S, Daniel J, Chen H, Celeste A, et al. ATM prevents the persistence and propagation of chromosome breaks in lymphocytes. Cell. 2007;130:63-75 pubmed
    DNA double-strand breaks (DSBs) induce a signal transmitted by the ataxia-telangiectasia mutated (ATM) kinase, which suppresses illegitimate joining of DSBs and activates cell-cycle checkpoints...
  24. Ashley T, Westphal C, Plug de Maggio A, de Rooij D. The mammalian mid-pachytene checkpoint: meiotic arrest in spermatocytes with a mutation in Atm alone or in combination with a Trp53 (p53) or Cdkn1a (p21/cip1) mutation. Cytogenet Genome Res. 2004;107:256-62 pubmed
    b>ATM, the protein product of the gene mutated in the human autosomal recessive disorder ataxia telangiectasia, is involved in detection of double strand breaks (DSBs) and is a key component of the damage surveillance network of cell cycle ..
  25. Liyanage M, Weaver Z, Barlow C, Coleman A, Pankratz D, Anderson S, et al. Abnormal rearrangement within the alpha/delta T-cell receptor locus in lymphomas from Atm-deficient mice. Blood. 2000;96:1940-6 pubmed
    b>Atm-deficient mice (Atm(-/-)) recapitulate many aspects of the ataxia telangiectasia (AT) syndrome, including the susceptibility to tumors of lymphoid origin...
  26. Bolcun Filas E, Rinaldi V, White M, Schimenti J. Reversal of female infertility by Chk2 ablation reveals the oocyte DNA damage checkpoint pathway. Science. 2014;343:533-6 pubmed publisher
  27. Eaton J, Lin Z, Sartorelli A, Bonawitz N, Shadel G. Ataxia-telangiectasia mutated kinase regulates ribonucleotide reductase and mitochondrial homeostasis. J Clin Invest. 2007;117:2723-34 pubmed
    Ataxia-telangiectasia mutated (ATM) kinase orchestrates nuclear DNA damage responses but is proposed to be involved in other important and clinically relevant functions...
  28. Bellani M, Romanienko P, Cairatti D, Camerini Otero R. SPO11 is required for sex-body formation, and Spo11 heterozygosity rescues the prophase arrest of Atm-/- spermatocytes. J Cell Sci. 2005;118:3233-45 pubmed
    ..We investigated the role in meiosis of the three kinases [ATM (ataxia telangiectasia mutated), ATR (ataxia-telangiectasia- and Rad-3-related) and DNA-PKcs (DNA-dependent-protein-..
  29. Eilam R, Peter Y, Groner Y, Segal M. Late degeneration of nigro-striatal neurons in ATM-/- mice. Neuroscience. 2003;121:83-98 pubmed
    The generation of an Atm -/- mouse model of the human ataxia-telangiectasia (AT) opened new avenues toward a better understanding of the molecular and cellular basis of AT...
  30. Yamamoto K, Wang Y, Jiang W, Liu X, Dubois R, Lin C, et al. Kinase-dead ATM protein causes genomic instability and early embryonic lethality in mice. J Cell Biol. 2012;198:305-13 pubmed publisher
    Ataxia telangiectasia (A-T) mutated (ATM) kinase orchestrates deoxyribonucleic acid (DNA) damage responses by phosphorylating numerous substrates implicated in DNA repair and cell cycle checkpoint activation...
  31. Bailey S, Gurley K, Hoon Kim K, Kelly Spratt K, Kemp C. Tumor suppression by p53 in the absence of Atm. Mol Cancer Res. 2008;6:1185-92 pubmed publisher
    ..It was recently proposed that oncogenes can also induce DNA damage, and this can induce p53 through the Atm DNA damage pathway...
  32. Daugherity E, Balmus G, Al Saei A, Moore E, Abi Abdallah D, Rogers A, et al. The DNA damage checkpoint protein ATM promotes hepatocellular apoptosis and fibrosis in a mouse model of non-alcoholic fatty liver disease. Cell Cycle. 2012;11:1918-28 pubmed publisher
    ..Consistent with reports that the DNA damage checkpoint kinase Ataxia Telangiectasia Mutated (ATM) is activated by oxidative stress, ATM phosphorylation was induced in the livers of wild type mice following high ..
  33. Takubo K, Hirao A, Ohmura M, Azuma M, Arai F, Nagamatsu G, et al. Premeiotic germ cell defect in seminiferous tubules of Atm-null testis. Biochem Biophys Res Commun. 2006;351:993-8 pubmed
    ..It has been shown that ataxia telangiectasia-mutated (ATM) is required for meiotic division of the seminiferous tubules...
  34. Shreeram S, Demidov O, Hee W, Yamaguchi H, Onishi N, Kek C, et al. Wip1 phosphatase modulates ATM-dependent signaling pathways. Mol Cell. 2006;23:757-64 pubmed
    ..Here, we report that deficiency of Wip1 resulted in activation of the ataxia-telangiectasia mutated (ATM) kinase...
  35. Burma S, Chen B, Murphy M, Kurimasa A, Chen D. ATM phosphorylates histone H2AX in response to DNA double-strand breaks. J Biol Chem. 2001;276:42462-7 pubmed
    ..Although the phosphatidylinositol 3-kinases, DNA-PK (DNA-dependent protein kinase), ATM (ataxia telangiectasia mutated), and ATR (ATM and Rad3-related), have all been implicated in H2AX phosphorylation, ..
  36. Liu Q, Guntuku S, Cui X, Matsuoka S, Cortez D, Tamai K, et al. Chk1 is an essential kinase that is regulated by Atr and required for the G(2)/M DNA damage checkpoint. Genes Dev. 2000;14:1448-59 pubmed
    ..Taken together, these data indicate that Chk1 plays an essential role in the mammalian DNA damage checkpoint, embryonic development, and tumor suppression, and that Atr regulates Chk1. ..
  37. Savic V, Yin B, Maas N, Bredemeyer A, Carpenter A, Helmink B, et al. Formation of dynamic gamma-H2AX domains along broken DNA strands is distinctly regulated by ATM and MDC1 and dependent upon H2AX densities in chromatin. Mol Cell. 2009;34:298-310 pubmed publisher
    ..Although both ATM and DNA-PKcs generate gamma-H2AX, only ATM promotes gamma-H2AX formation to maximal distance and maintains gamma-..
  38. Denchi E, de Lange T. Protection of telomeres through independent control of ATM and ATR by TRF2 and POT1. Nature. 2007;448:1068-71 pubmed
    ..of the telomeric DNA or by inhibition of shelterin, cells show the hallmarks of ataxia telangiectasia mutated (ATM) kinase signalling...
  39. Spring K, Cross S, Li C, Watters D, Ben Senior L, Waring P, et al. Atm knock-in mice harboring an in-frame deletion corresponding to the human ATM 7636del9 common mutation exhibit a variant phenotype. Cancer Res. 2001;61:4561-8 pubmed
    b>ATM, the gene mutated in the human immunodeficiency disorder ataxia-telangiectasia (A-T), plays a central role in recognizing ionizing radiation damage in DNA and in controlling several cell cycle checkpoints...
  40. Jiang H, Reinhardt H, Bartkova J, Tommiska J, Blomqvist C, Nevanlinna H, et al. The combined status of ATM and p53 link tumor development with therapeutic response. Genes Dev. 2009;23:1895-909 pubmed publisher
    ..Specifically, evaluation of the combined status of ATM and p53, two commonly mutated tumor suppressor genes, can help to predict the clinical response to genotoxic ..
  41. Ramiro A, Jankovic M, Callen E, Difilippantonio S, Chen H, McBride K, et al. Role of genomic instability and p53 in AID-induced c-myc-Igh translocations. Nature. 2006;440:105-9 pubmed
    ..In addition, translocations are inhibited by the tumour suppressors ATM, Nbs1, p19 (Arf) and p53, which is consistent with activation of DNA damage- and oncogenic stress-induced ..
  42. Liao M, Van Dyke T. Critical role for Atm in suppressing V(D)J recombination-driven thymic lymphoma. Genes Dev. 1999;13:1246-50 pubmed
    ..T cell receptor (TCR) loci have been found in tumors from Ataxia telangiectasia (AT) patients and in mouse Atm-/- thymoma, suggesting the involvement of V(D)J recombination in these malignancies...
  43. Difilippantonio S, Celeste A, Kruhlak M, Lee Y, Difilippantonio M, Feigenbaum L, et al. Distinct domains in Nbs1 regulate irradiation-induced checkpoints and apoptosis. J Exp Med. 2007;204:1003-11 pubmed
    ..The NBS protein Nbs1 is not only a downstream target of AT mutated (ATM) kinase but also acts upstream, promoting optimal ATM activation, ATM recruitment to breaks, and ATM accessibility ..
  44. Shin Y, Choi Y, Erdin S, Yatsenko S, Kloc M, Yang F, et al. Hormad1 mutation disrupts synaptonemal complex formation, recombination, and chromosome segregation in mammalian meiosis. PLoS Genet. 2010;6:e1001190 pubmed publisher
    ..HORMAD1 is therefore a critical component of the synaptonemal complex that affects synapsis, recombination, and meiotic sex chromosome inactivation and transcriptional silencing...
  45. Spring K, Ahangari F, Scott S, Waring P, Purdie D, Chen P, et al. Mice heterozygous for mutation in Atm, the gene involved in ataxia-telangiectasia, have heightened susceptibility to cancer. Nat Genet. 2002;32:185-90 pubmed
    ..Heterozygous carriers of ATM, the gene defective in ataxia-telangiectasia, have a higher than normal risk of developing breast and other cancers...
  46. Ménisser de Murcia J, Mark M, Wendling O, Wynshaw Boris A, de Murcia G. Early embryonic lethality in PARP-1 Atm double-mutant mice suggests a functional synergy in cell proliferation during development. Mol Cell Biol. 2001;21:1828-32 pubmed
    PARP-1 and ATM are both involved in the response to DNA strand breaks, resulting in induction of a signaling network responsible for DNA surveillance, cellular recovery, and cell survival...
  47. Umesako S, Fujisawa K, Iiga S, Mori N, Takahashi M, Hong D, et al. Atm heterozygous deficiency enhances development of mammary carcinomas in p53 heterozygous knockout mice. Breast Cancer Res. 2005;7:R164-70 pubmed
    ..Although ataxia-telangiectasia mutated (ATM) heterozygous deficiency has been proposed to increase susceptibility to breast cancer, some studies have not found ..
  48. Barlow C, Dennery P, Shigenaga M, Smith M, Morrow J, Roberts L, et al. Loss of the ataxia-telangiectasia gene product causes oxidative damage in target organs. Proc Natl Acad Sci U S A. 1999;96:9915-9 pubmed
    ..To assess this hypothesis, we employed an animal model of A-T, the mouse with a disrupted Atm gene...
  49. Liu N, Stoica G, Yan M, Scofield V, Qiang W, Lynn W, et al. ATM deficiency induces oxidative stress and endoplasmic reticulum stress in astrocytes. Lab Invest. 2005;85:1471-80 pubmed
    b>ATM kinase, the product of the ataxia telangiectasia mutated (Atm) gene, is activated by genomic damage. ATM plays a crucial role in cell growth and development...
  50. Shreeram S, Hee W, Demidov O, Kek C, Yamaguchi H, Fornace A, et al. Regulation of ATM/p53-dependent suppression of myc-induced lymphomas by Wip1 phosphatase. J Exp Med. 2006;203:2793-9 pubmed
    The ataxia telangiectasia mutated (ATM) kinase is a key tumor suppressor that regulates numerous cell cycle checkpoints as well as apoptosis...
  51. Callén E, Jankovic M, Wong N, Zha S, Chen H, Difilippantonio S, et al. Essential role for DNA-PKcs in DNA double-strand break repair and apoptosis in ATM-deficient lymphocytes. Mol Cell. 2009;34:285-97 pubmed publisher
    The DNA double-strand break (DSB) repair protein DNA-PKcs and the signal transducer ATM are both activated by DNA breaks and phosphorylate similar substrates in vitro, yet appear to have distinct functions in vivo...
  52. Lumsden J, McCarty T, Petiniot L, Shen R, Barlow C, Wynn T, et al. Immunoglobulin class switch recombination is impaired in Atm-deficient mice. J Exp Med. 2004;200:1111-21 pubmed
    ..Because the protein kinase ataxia telengiectasia (AT) mutated (ATM) plays a critical role in DSB repair and AT patients show abnormalities of Ig isotype expression, we assessed the ..
  53. Wilda M, Demuth I, Concannon P, Sperling K, Hameister H. Expression pattern of the Nijmegen breakage syndrome gene, Nbs1, during murine development. Hum Mol Genet. 2000;9:1739-44 pubmed
    ..These expression patterns suggest that in addition to the role of the Nbs1 gene product as part of a DNA DSB repair complex, the Nbs1 gene product may serve further functions during development. ..
  54. Li M, Fang X, Baker D, Guo L, Gao X, Wei Z, et al. The ATM-p53 pathway suppresses aneuploidy-induced tumorigenesis. Proc Natl Acad Sci U S A. 2010;107:14188-93 pubmed publisher
    ..The p53 activation depends on the ataxia-telangiectasia mutated (ATM) gene product and increased levels of reactive oxygen species...
  55. Kang J, Ferguson D, Song H, Bassing C, Eckersdorff M, Alt F, et al. Functional interaction of H2AX, NBS1, and p53 in ATM-dependent DNA damage responses and tumor suppression. Mol Cell Biol. 2005;25:661-70 pubmed
    Ataxia-telangiectasia (A-T) mutated (ATM) kinase signals all three cell cycle checkpoints after DNA double-stranded break (DSB) damage...
  56. Helmink B, Bredemeyer A, Lee B, Huang C, Sharma G, Walker L, et al. MRN complex function in the repair of chromosomal Rag-mediated DNA double-strand breaks. J Exp Med. 2009;206:669-79 pubmed publisher
    ..repair of DNA DSBs and in the initiation of DSB responses through activation of the ataxia telangiectasia-mutated (ATM) serine-threonine kinase...
  57. Orii K, Lee Y, Kondo N, McKinnon P. Selective utilization of nonhomologous end-joining and homologous recombination DNA repair pathways during nervous system development. Proc Natl Acad Sci U S A. 2006;103:10017-22 pubmed
    ..Moreover, DNA damage-induced apoptosis required the ataxia telangiectasia mutated (Atm) kinase after disruption of NHEJ, but not HR, during neurogenesis...
  58. Dar I, Yosha G, Elfassy R, Galron R, Wang Z, Shiloh Y, et al. Investigation of the functional link between ATM and NBS1 in the DNA damage response in the mouse cerebellum. J Biol Chem. 2011;286:15361-76 pubmed publisher
    ..Among others, Mre11/RAD50/NBS1 is required for timely activation of the protein kinase ATM (A-T, mutated), which is missing or inactivated in patients with A-T...
  59. Gurley K, Kemp C. Synthetic lethality between mutation in Atm and DNA-PK(cs) during murine embryogenesis. Curr Biol. 2001;11:191-4 pubmed
    The gene product mutated in ataxia telangiectasia, ATM, is a ubiquitously expressed 370 kDa protein kinase that is a key mediator of the cellular response to DNA damage [1]...
  60. FOSTER C, Daniel L, Daniels C, Dalal S, Singh M, Singh K. Deficiency of ataxia telangiectasia mutated kinase modulates cardiac remodeling following myocardial infarction: involvement in fibrosis and apoptosis. PLoS ONE. 2013;8:e83513 pubmed publisher
    Ataxia telangiectasia mutated kinase (ATM) is a cell cycle checkpoint protein activated in response to DNA damage. We recently reported that ATM plays a protective role in myocardial remodeling following ?-adrenergic receptor stimulation...
  61. Smilenov L, Lieberman H, Mitchell S, Baker R, Hopkins K, Hall E. Combined haploinsufficiency for ATM and RAD9 as a factor in cell transformation, apoptosis, and DNA lesion repair dynamics. Cancer Res. 2005;65:933-8 pubmed
    ..To address this issue, primary mouse cells, haploinsufficient for one or two proteins, ATM and RAD9, related to the cellular response to DNA damage were examined...
  62. Li J, Chen J, Vinters H, Gatti R, Herrup K. Stable brain ATM message and residual kinase-active ATM protein in ataxia-telangiectasia. J Neurosci. 2011;31:7568-77 pubmed publisher
    The gene that is mutated in ataxia-telangiectasia (A-T), ATM, is catalytically activated in response to DNA damage. Yet a full accounting for the CNS deficits in human A-T or its mouse models remains elusive...
  63. Petiniot L, Weaver Z, Barlow C, Shen R, Eckhaus M, Steinberg S, et al. Recombinase-activating gene (RAG) 2-mediated V(D)J recombination is not essential for tumorigenesis in Atm-deficient mice. Proc Natl Acad Sci U S A. 2000;97:6664-9 pubmed
    The majority of Atm-deficient mice die of malignant thymic lymphoma by 4-5 mo of age...
  64. Yang Y, Herrup K. Loss of neuronal cell cycle control in ataxia-telangiectasia: a unified disease mechanism. J Neurosci. 2005;25:2522-9 pubmed
    In ataxia-telangiectasia (A-T), the loss of the ataxia-telangiectasia mutated (ATM) kinase leads to a failure of cell cycle checkpoints and DNA double-strand break detection resulting in cellular radiation sensitivity and a ..
  65. Worgul B, Smilenov L, Brenner D, Junk A, Zhou W, Hall E. Atm heterozygous mice are more sensitive to radiation-induced cataracts than are their wild-type counterparts. Proc Natl Acad Sci U S A. 2002;99:9836-9 pubmed
    ..Although cells heterozygous for the ATM gene (ATM(+/-)) may be slightly more radiosensitive in vitro, it remained to be determined whether the greater ..
  66. Reina San Martin B, Chen H, Nussenzweig A, Nussenzweig M. ATM is required for efficient recombination between immunoglobulin switch regions. J Exp Med. 2004;200:1103-10 pubmed
    Ataxia telangiectasia mutated (ATM) kinase is critical for initiating the signaling pathways that lead to cell cycle checkpoints and DNA double strand break repair...
  67. Frappart P, Lee Y, Lamont J, McKinnon P. BRCA2 is required for neurogenesis and suppression of medulloblastoma. EMBO J. 2007;26:2732-42 pubmed
    ..In contrast, loss of the Atm kinase did not markedly attenuate apoptosis after Brca2 loss, but did partially restore cerebellar morphology, ..
  68. Deriano L, Chaumeil J, Coussens M, Multani A, Chou Y, Alekseyenko A, et al. The RAG2 C terminus suppresses genomic instability and lymphomagenesis. Nature. 2011;471:119-23 pubmed publisher
    ..Defects in DNA damage response factors such as ataxia telangiectasia mutated (ATM) protein and combined deficiencies in classical non-homologous end joining and p53 predispose to RAG-initiated ..
  69. Kwong L, Weiss K, Haigis K, Dove W. Atm is a negative regulator of intestinal neoplasia. Oncogene. 2008;27:1013-8 pubmed
    The ataxia telangiectasia-mutated (ATM) gene has been implicated as an early barrier to the growth and progression of incipient solid tumors...
  70. Mahowald G, Baron J, Mahowald M, Kulkarni S, Bredemeyer A, Bassing C, et al. Aberrantly resolved RAG-mediated DNA breaks in Atm-deficient lymphocytes target chromosomal breakpoints in cis. Proc Natl Acad Sci U S A. 2009;106:18339-44 pubmed publisher
    ..However, in ataxia telangiectasia mutated (ATM)-deficient lymphocytes, RAG breaks are frequently joined aberrantly, forming chromosomal lesions such as ..
  71. Huang C, Sharma G, Walker L, Bassing C, Pandita T, Sleckman B. Defects in coding joint formation in vivo in developing ATM-deficient B and T lymphocytes. J Exp Med. 2007;204:1371-81 pubmed
    Ataxia-telangiectasia mutated (ATM)-deficient lymphocytes exhibit defects in coding joint formation during V(D)J recombination in vitro...
  72. Liao M, Yin C, Barlow C, Wynshaw Boris A, Van Dyke T. Atm is dispensable for p53 apoptosis and tumor suppression triggered by cell cycle dysfunction. Mol Cell Biol. 1999;19:3095-102 pubmed
    Both p53 and ATM are checkpoint regulators with roles in genetic stabilization and cancer susceptibility. ATM appears to function in the same DNA damage checkpoint pathway as p53...
  73. Watanabe F, Fukazawa H, Masutani M, Suzuki H, Teraoka H, Mizutani S, et al. Poly(ADP-ribose) polymerase-1 inhibits ATM kinase activity in DNA damage response. Biochem Biophys Res Commun. 2004;319:596-602 pubmed
    ..mobilize DNA-repair machinery and cell cycle checkpoint by activating the ataxia-telangiectasia (A-T) mutated (ATM). Here we show that ATM kinase activity is inhibited by poly(ADP-ribose) polymerase-1 (PARP-1) in vitro...
  74. Smilenov L, Brenner D, Hall E. Modest increased sensitivity to radiation oncogenesis in ATM heterozygous versus wild-type mammalian cells. Cancer Res. 2001;61:5710-3 pubmed
    ..between wild-type mouse embryo fibroblasts and mouse embryo fibroblasts carrying ataxia telangiectasia mutated (ATM) null mutation indicate that the heterozygous cells are more sensitive to radiation oncogenesis than their normal, ..
  75. Miles P, Treuner K, Latronica M, Olefsky J, Barlow C. Impaired insulin secretion in a mouse model of ataxia telangiectasia. Am J Physiol Endocrinol Metab. 2007;293:E70-4 pubmed
    Ataxia telangiectasia (A-T) is an autosomal recessive disease caused by mutations in the A-T mutated (ATM) gene...
  76. Viniegra J, Martinez N, Modirassari P, Hernandez Losa J, Parada Cobo C, Sánchez Arévalo Lobo V, et al. Full activation of PKB/Akt in response to insulin or ionizing radiation is mediated through ATM. J Biol Chem. 2005;280:4029-36 pubmed
    The gene mutated in ataxia telangiectasia, ATM, has been implicated in several cell functions such as cell cycle control and response to DNA damage and insulin...
  77. Barlow C, Ribaut Barassin C, Zwingman T, Pope A, Brown K, Owens J, et al. ATM is a cytoplasmic protein in mouse brain required to prevent lysosomal accumulation. Proc Natl Acad Sci U S A. 2000;97:871-6 pubmed
    We previously generated a mouse model with a mutation in the murine Atm gene that recapitulates many aspects of the childhood neurodegenerative disease ataxia-telangiectasia...
  78. Lange J, Pan J, Cole F, Thelen M, Jasin M, Keeney S. ATM controls meiotic double-strand-break formation. Nature. 2011;479:237-40 pubmed publisher
    ..Here we report that the number of meiotic DSBs in mouse is controlled by ATM, a kinase activated by DNA damage to trigger checkpoint signalling and promote DSB repair...
  79. Zha S, Jiang W, Fujiwara Y, Patel H, Goff P, Brush J, 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;108:2028-33 pubmed publisher
    ..DNA-PKcs and the ataxia telangiectasia-mutated (ATM) kinase are members of the same family, and they share common substrates in the DNA damage response...
  80. Lu S, Shen K, Wang Y, Santner S, Chen J, Brooks S, et al. Atm-haploinsufficiency enhances susceptibility to carcinogen-induced mammary tumors. Carcinogenesis. 2006;27:848-55 pubmed
    Ataxia-telangiectasia (A-T), which is due to mutations in the ATM gene, is a rare autosomal recessive genomic instability syndrome characterized by radiosensitivity and predisposition to cancer...
  81. Gapud E, Dorsett Y, Yin B, Callen E, Bredemeyer A, Mahowald G, et al. Ataxia telangiectasia mutated (Atm) and DNA-PKcs kinases have overlapping activities during chromosomal signal joint formation. Proc Natl Acad Sci U S A. 2011;108:2022-7 pubmed publisher
    ..RAG DSBs are generated in G1-phase developing lymphocytes, where they activate the ataxia telangiectasia mutated (Atm) and DNA-PKcs kinases to orchestrate diverse cellular DNA damage responses including DSB repair...
  82. Di Giacomo M, Barchi M, Baudat F, Edelmann W, Keeney S, Jasin M. Distinct DNA-damage-dependent and -independent responses drive the loss of oocytes in recombination-defective mouse mutants. Proc Natl Acad Sci U S A. 2005;102:737-42 pubmed
    ..these findings as a paradigm, we also examined oocyte loss in mutants lacking the DNA-damage checkpoint kinase ATM. The absence of ATM caused defects in folliculogenesis that were similar to those in Dmc1 mutants and that could be ..
  83. Shen K, Heng H, Wang Y, Lu S, Liu G, Deng C, et al. ATM and p21 cooperate to suppress aneuploidy and subsequent tumor development. Cancer Res. 2005;65:8747-53 pubmed
    The DNA damage checkpoint protein kinase mutated in ataxia telangiectasia (ATM) is involved in sensing and transducing DNA damage signals by phosphorylating and activating downstream target proteins that are implicated in the regulation ..