ataxia telangiectasia

Summary

Summary: An autosomal recessive inherited disorder characterized by choreoathetosis beginning in childhood, progressive CEREBELLAR ATAXIA; TELANGIECTASIS of CONJUNCTIVA and SKIN; DYSARTHRIA; B- and T-cell immunodeficiency, and RADIOSENSITIVITY to IONIZING RADIATION. Affected individuals are prone to recurrent sinobronchopulmonary infections, lymphoreticular neoplasms, and other malignancies. Serum ALPHA-FETOPROTEINS are usually elevated. (Menkes, Textbook of Child Neurology, 5th ed, p688) The gene for this disorder (ATM) encodes a cell cycle checkpoint protein kinase and has been mapped to chromosome 11 (11q22-q23).

Top Publications

  1. pmc Nuclear accumulation of HDAC4 in ATM deficiency promotes neurodegeneration in ataxia telangiectasia
    Jiali Li
    Department of Cell Biology and Neuroscience, Nelson Biological Laboratories, Rutgers University, Piscataway, New Jersey, USA
    Nat Med 18:783-90. 2012
  2. ncbi Atm-deficient mice: a paradigm of ataxia telangiectasia
    C Barlow
    Laboratory of Genetic Disease Research, National Center for Human Genome Research, National Institutes of Health, Bethesda, Maryland 20892, USA
    Cell 86:159-71. 1996
  3. doi Ataxia-telangiectasia: from a rare disorder to a paradigm for cell signalling and cancer
    Martin F Lavin
    Radiation Biology and Oncology Laboratory, Queensland Institute of Medical Research, Brisbane, QLD 4029, Australia
    Nat Rev Mol Cell Biol 9:759-69. 2008
  4. doi The role of the DNA damage response in neuronal development, organization and maintenance
    Ari Barzilai
    Department of Neurobiology, George S Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv 69978, Israel
    DNA Repair (Amst) 7:1010-27. 2008
  5. pmc Donor-derived brain tumor following neural stem cell transplantation in an ataxia telangiectasia patient
    Ninette Amariglio
    Cancer Research Center, Sheba Medical Center and Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
    PLoS Med 6:e1000029. 2009
  6. ncbi Localization of an ataxia-telangiectasia gene to chromosome 11q22-23
    R A Gatti
    Department of Pathology, UCLA School of Medicine 90024
    Nature 336:577-80. 1988
  7. ncbi Inactivation of ataxia telangiectasia mutated gene in B-cell chronic lymphocytic leukaemia
    T Stankovic
    CRC Institute for Cancer Studies, Medical School, University of Birmingham, Edgbaston, UK
    Lancet 353:26-9. 1999
  8. ncbi Ataxia-telangiectasia, an evolving phenotype
    Helen H Chun
    Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095 1732, USA
    DNA Repair (Amst) 3:1187-96. 2004
  9. ncbi Joining of correct and incorrect DNA double-strand break ends in normal human and ataxia telangiectasia fibroblasts
    M Lobrich
    Strahlenzentrum der Justus Liebig Universität Giessen, Germany
    Genes Chromosomes Cancer 27:59-68. 2000
  10. ncbi ATM and related protein kinases: safeguarding genome integrity
    Yosef Shiloh
    The David and Inez Myers Laboratory for Genetic Research, Department of Human Genetics and Molecular Medicine, Sackler School of Medicine, Tel Aviv University, Tel Aviv 69978, Israel
    Nat Rev Cancer 3:155-68. 2003

Detail Information

Publications352 found, 100 shown here

  1. pmc Nuclear accumulation of HDAC4 in ATM deficiency promotes neurodegeneration in ataxia telangiectasia
    Jiali Li
    Department of Cell Biology and Neuroscience, Nelson Biological Laboratories, Rutgers University, Piscataway, New Jersey, USA
    Nat Med 18:783-90. 2012
    b>Ataxia telangiectasia is a neurodegenerative disease caused by mutation of the Atm gene...
  2. ncbi Atm-deficient mice: a paradigm of ataxia telangiectasia
    C Barlow
    Laboratory of Genetic Disease Research, National Center for Human Genome Research, National Institutes of Health, Bethesda, Maryland 20892, USA
    Cell 86:159-71. 1996
    A murine model of ataxia telangiectasia was created by disrupting the Atm locus via gene targeting...
  3. doi Ataxia-telangiectasia: from a rare disorder to a paradigm for cell signalling and cancer
    Martin F Lavin
    Radiation Biology and Oncology Laboratory, Queensland Institute of Medical Research, Brisbane, QLD 4029, Australia
    Nat Rev Mol Cell Biol 9:759-69. 2008
    ....
  4. doi The role of the DNA damage response in neuronal development, organization and maintenance
    Ari Barzilai
    Department of Neurobiology, George S Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv 69978, Israel
    DNA Repair (Amst) 7:1010-27. 2008
    ..This review focuses on the DNA damage response in neuronal cells and points to the importance of this elaborate network to the integrity of the nervous system from its early development and throughout the lifetime of the organism...
  5. pmc Donor-derived brain tumor following neural stem cell transplantation in an ataxia telangiectasia patient
    Ninette Amariglio
    Cancer Research Center, Sheba Medical Center and Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
    PLoS Med 6:e1000029. 2009
    ..However, concerns have been raised over the safety of this experimental therapeutic approach, including, for example, whether there is the potential for tumors to develop from transplanted stem cells...
  6. ncbi Localization of an ataxia-telangiectasia gene to chromosome 11q22-23
    R A Gatti
    Department of Pathology, UCLA School of Medicine 90024
    Nature 336:577-80. 1988
    ..This has allowed us to localize a gene for AT to chromosomal region 11q22-23...
  7. ncbi Inactivation of ataxia telangiectasia mutated gene in B-cell chronic lymphocytic leukaemia
    T Stankovic
    CRC Institute for Cancer Studies, Medical School, University of Birmingham, Edgbaston, UK
    Lancet 353:26-9. 1999
    Patients with the inherited disorder ataxia telangiectasia (A-T) have an increased susceptibility to lymphoid malignancies. In these patients mutations affect both alleles of the A-T gene (ATM)...
  8. ncbi Ataxia-telangiectasia, an evolving phenotype
    Helen H Chun
    Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095 1732, USA
    DNA Repair (Amst) 3:1187-96. 2004
    ..The term "A-T variant" has a diminishing usefulness...
  9. ncbi Joining of correct and incorrect DNA double-strand break ends in normal human and ataxia telangiectasia fibroblasts
    M Lobrich
    Strahlenzentrum der Justus Liebig Universität Giessen, Germany
    Genes Chromosomes Cancer 27:59-68. 2000
    ..and incorrect break ends were further investigated in cells from a patient with the cancer-prone disease ataxia telangiectasia (AT) and in heterozygous AT cells...
  10. ncbi ATM and related protein kinases: safeguarding genome integrity
    Yosef Shiloh
    The David and Inez Myers Laboratory for Genetic Research, Department of Human Genetics and Molecular Medicine, Sackler School of Medicine, Tel Aviv University, Tel Aviv 69978, Israel
    Nat Rev Cancer 3:155-68. 2003
    ..Understanding ATM's mode of action provides new insights into the association between defective responses to DNA damage and cancer, and brings us closer to resolving the issue of cancer predisposition in some A-T carriers...
  11. ncbi Stress-induced premature senescence in hTERT-expressing ataxia telangiectasia fibroblasts
    Kazuhito Naka
    Department of Geriatric Research, National Institute for Longevity Sciences, 36 3 Gengo, Morioka, Obu 474 8522, Japan
    J Biol Chem 279:2030-7. 2004
    ..ATM, the product of the gene mutated in individuals with ataxia telangiectasia (AT), plays a central role in cell cycle arrest in response to DNA damage...
  12. ncbi Localization of a portion of extranuclear ATM to peroxisomes
    D Watters
    Cancer Research Unit, Queensland Institute of Medical Research, Royal Brisbane Hospital, Herston, Brisbane, Australia, 4029
    J Biol Chem 274:34277-82. 1999
    ..Significantly decreased catalase activity and increased lipid peroxidation was observed in several A-T cell lines. The localization of ATM to peroxisomes may contribute to the pleiotropic nature of A-T...
  13. pmc Functional characterization and targeted correction of ATM mutations identified in Japanese patients with ataxia-telangiectasia
    Kotoka Nakamura
    Department of Pathology and Laboratory Medicine, UCLA School of Medicine, Los Angeles, California 90095 1732, USA
    Hum Mutat 33:198-208. 2012
    ....
  14. pmc Underexpression and abnormal localization of ATM products in ataxia telangiectasia patients bearing ATM missense mutations
    Virginie Jacquemin
    Institut Curie, Centre de Recherche, Paris, France
    Eur J Hum Genet 20:305-12. 2012
    b>Ataxia telangiectasia (A-T) is a rare autosomal recessive disorder characterized by progressive cerebellar ataxia, oculocutaneous telangiectasia, immune defects and predisposition to malignancies...
  15. doi Cytoplasmic ATM protein kinase: an emerging therapeutic target for diabetes, cancer and neuronal degeneration
    Da Qing Yang
    The Sanford Project, Sanford Research USD, Sanford Health, and the Department of Pediatrics, Sanford School of Medicine of the University of South Dakota, 2301 East 60th Street North, Sioux Falls, SD 57104, USA
    Drug Discov Today 16:332-8. 2011
    ..The potential for cytoplasmic ATM protein kinase to be an emerging therapeutic target for treating diabetes, cancer and neuronal degeneration is discussed...
  16. doi The neuro-glial-vascular interrelations in genomic instability symptoms
    Ari Barzilai
    Department of Neurobiology, George S Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv 69978, Israel
    Mech Ageing Dev 132:395-404. 2011
    ..Here I describe various aspects of neural and glial cell fate and the vascular system in genomic instability disorders including ataxia telangiectasia (A-T) and Nijmegen breakage syndrome.
  17. doi ATM and the molecular pathogenesis of ataxia telangiectasia
    Peter J McKinnon
    Department of Genetics, St Jude Children s Research Hospital, Memphis, Tennessee 38105, USA
    Annu Rev Pathol 7:303-21. 2012
    b>Ataxia telangiectasia (A-T) results from inactivation of the ATM protein kinase. DNA-damage signaling is a prime function of this kinase, although other roles have been ascribed to ATM...
  18. ncbi ATM deficiency and oxidative stress: a new dimension of defective response to DNA damage
    Ari Barzilai
    Department of Neurobiochemistry, George S Wise Faculty of Life Sciences, Tel Aviv University, 69978, Tel Aviv, Israel
    DNA Repair (Amst) 1:3-25. 2002
    ..This connection may provide new insights into the phenotypes associated with genetic deficiencies of DNA damage responses, and point to new strategies to alleviate some of their clinical symptoms...
  19. ncbi Early diagnosis of ataxia-telangiectasia using radiosensitivity testing
    Xia Sun
    Department of Pathology, UCLA School of Medicine, Los Angeles, California 90095 1732, USA
    J Pediatr 140:724-31. 2002
    ..To utilize radiosensitivity testing to improve early diagnosis of patients with ataxia-telangiectasia (A-T)...
  20. ncbi Loss of neuronal cell cycle control in ataxia-telangiectasia: a unified disease mechanism
    Yan Yang
    Department of Neurology, Alzheimer Research Laboratory E504, Case School of Medicine, Cleveland, Ohio 44106, USA
    J Neurosci 25:2522-9. 2005
    ..These results suggest that loss of cell cycle control represents a common disease mechanism that underlies the defects in the affected tissues in both human and mouse diseases...
  21. pmc Cytoplasmic ATM in neurons modulates synaptic function
    Jiali Li
    Department of Cell Biology and Neuroscience, Rutgers University, Piscataway, NJ 08854, USA
    Curr Biol 19:2091-6. 2009
    ..Also, cytoplasmic ATM physically associates with the homologous PI 3-kinase, ATR. The neurological symptoms of ataxia-telangiectasia may thus result from defective nonnuclear functions of ATM not associated with DNA repair...
  22. pmc Molecular pathology of ataxia telangiectasia
    A M R Taylor
    CR UK Institute for Cancer Studies, University of Birmingham, Vincent Drive, Edgbaston, Birmingham B15 2TT, UK
    J Clin Pathol 58:1009-15. 2005
    b>Ataxia telangiectasia (A-T) is one of a group of autosomal recessive cerebellar ataxias...
  23. pmc Differential DNA damage signaling accounts for distinct neural apoptotic responses in ATLD and NBS
    Erin R P Shull
    Department of Genetics and Tumor Cell Biology, St Jude Children s Research Hospital, Memphis, Tennessee 38105, USA
    Genes Dev 23:171-80. 2009
    The MRN complex (Mre11/RAD50/NBS1) and ATM (ataxia telangiectasia, mutated) are critical for the cellular response to DNA damage...
  24. ncbi Somatic ATM mutations indicate a pathogenic role of ATM in B-cell chronic lymphocytic leukemia
    C Schaffner
    Abteilung Organisation komplexer Genome, Deutsches Krebsforschungszentrum, Heidelberg, Germany
    Blood 94:748-53. 1999
    ..Our study demonstrates somatic disruption of both alleles of the ATM gene by deletion or point mutation and thus its pathogenic role in sporadic B-cell lineage tumors...
  25. ncbi Intrinsic mitochondrial dysfunction in ATM-deficient lymphoblastoid cells
    Mark Ambrose
    Department of Pathology and Laboratory Medicine, University of California, Los Angeles, CA 90095 1732, USA
    Hum Mol Genet 16:2154-64. 2007
    One of the characteristic features of cells from patients with ataxia telangiectasia (A-T) is that they are in a state of continuous oxidative stress and exhibit constitutive activation of pathways that normally respond to oxidative ..
  26. ncbi A single ataxia telangiectasia gene with a product similar to PI-3 kinase
    K Savitsky
    Department of Human Genetics, Sackler School of Medicine, Tel Aviv University, Israel
    Science 268:1749-53. 1995
    A gene, ATM, that is mutated in the autosomal recessive disorder ataxia telangiectasia (AT) was identified by positional cloning on chromosome 11q22-23...
  27. ncbi TEL1, an S. cerevisiae homolog of the human gene mutated in ataxia telangiectasia, is functionally related to the yeast checkpoint gene MEC1
    D M Morrow
    Department of Molecular Biology and Genetics, Johns Hopkins School of Medicine, Baltimore, Maryland 21205, USA
    Cell 82:831-40. 1995
    Patients with the genetic disorder ataxia telangiectasia (AT) have mutations in the AT mutated (ATM) gene, which is homologous to TEL1 and the checkpoint gene MEC1...
  28. doi Assessing the role of stress signalling via p38 MAP kinase in the premature senescence of ataxia telangiectasia and Werner syndrome fibroblasts
    Terence Davis
    Department of Pathology, Cardiff University, Heath Park, Cardiff, CF14 4XN, UK
    Biogerontology 10:253-66. 2009
    The premature ageing ataxia telangiectasia (AT) and Werner syndromes (WS) are associated with accelerated cellular ageing...
  29. doi The neurological phenotype of ataxia-telangiectasia: solving a persistent puzzle
    Sharon Biton
    Department of Human Molecular Genetics and Biochemistry, Sackler School of Medicine, Tel Aviv University, Tel Aviv 69978, Israel
    DNA Repair (Amst) 7:1028-38. 2008
    ..A-T remains a prototype disease for the study of the DDR's role in CNS development and maintenance...
  30. ncbi Characterization of ATM gene mutations in 66 ataxia telangiectasia families
    N Sandoval
    Department of Genome Analysis, Institute of Molecular Biotechnology, Jena, Germany, Institute of Human Genetics, Medical School Hannover, D 30625 Hannover, Germany
    Hum Mol Genet 8:69-79. 1999
    b>Ataxia telangiectasia (AT) is an autosomal recessive disease characterized by neurological and immunological symptoms, radiosensitivity and cancer predisposition...
  31. doi SMRT compounds abrogate cellular phenotypes of ataxia telangiectasia in neural derivatives of patient-specific hiPSCs
    Peiyee Lee
    Eli and Edythe Broad Center for Regenerative Medicine, UCLA, Los Angeles, California 90095, USA
    Nat Commun 4:1824. 2013
    b>Ataxia telangiectasia is a devastating neurodegenerative disease caused primarily by loss of function mutations in ATM, a hierarchical DNA repair gene and tumour suppressor...
  32. ncbi Role for ATM in DNA damage-induced phosphorylation of BRCA1
    M Gatei
    Queensland Institute of Medical Research, The University of Queensland, Royal Brisbane Hospital, Australia
    Cancer Res 60:3299-304. 2000
    ..This interaction between ATM and BRCA1 argues in favor of the involvement of particular aspects of ATM function in breast cancer predisposition...
  33. pmc Newborn screening for SCID identifies patients with ataxia telangiectasia
    Jacob Mallott
    Department of Pediatrics, University of California San Francisco, San Francisco, CA 94143 0519, USA
    J Clin Immunol 33:540-9. 2013
    ..Deep sequencing was employed to find causes of T lymphocytopenia in such infants...
  34. ncbi ATM mutations that cause ataxia-telangiectasia are breast cancer susceptibility alleles
    Anthony Renwick
    Section of Cancer Genetics, Institute of Cancer Research, 15 Cotswold Road, Sutton, Surrey, SM2 5NG, UK
    Nat Genet 38:873-5. 2006
    ..37 (95% confidence interval (c.i.) = 1.51-3.78, P = 0.0003). There was no evidence that other classes of ATM variant confer a risk of breast cancer...
  35. pmc Stable brain ATM message and residual kinase-active ATM protein in ataxia-telangiectasia
    Jiali Li
    Department of Cell Biology and Neuroscience, Nelson Biological Laboratories, Rutgers University, Piscataway, New Jersey 08854, USA
    J Neurosci 31:7568-77. 2011
    ..These findings offer important new insights into the human disease and the role of brain ATM activity in the severity of the neurological symptoms of A-T...
  36. pmc Structure of an aprataxin-DNA complex with insights into AOA1 neurodegenerative disease
    Percy Tumbale
    Laboratory of Structural Biology, National Institute of Environmental Health Sciences, US National Institutes of Health, Department of Health and Human Services, North Carolina, USA
    Nat Struct Mol Biol 18:1189-95. 2011
    ....
  37. doi Presence of ATM protein and residual kinase activity correlates with the phenotype in ataxia-telangiectasia: a genotype-phenotype study
    Mijke M M Verhagen
    Department of Pediatric Neurology, Radboud University Nijmegen Medical Centre, Donders Institute for Brain, Cognition and Behaviour, Nijmegen, The Netherlands
    Hum Mutat 33:561-71. 2012
    ..Each patient is left with a tremendously increased cancer risk...
  38. ncbi ATM stabilizes DNA double-strand-break complexes during V(D)J recombination
    Andrea L Bredemeyer
    Department of Pathology and Immunology, Washington University School of Medicine, St Louis, Missouri 63110, USA
    Nature 442:466-70. 2006
    ....
  39. ncbi ATM, a central controller of cellular responses to DNA damage
    K K Khanna
    The Queensland Institute of Medical Research, and Department of Pathology and Surgery, University of Queensland, PO Royal Brisbane Hospital, Brisbane, QLD4029, Australia
    Cell Death Differ 8:1052-65. 2001
    ..ATM also functions in the regulation of DNA repair and apoptosis, suggesting that it is a central regulator of responses to DNA double-strand breaks...
  40. doi Intrinsic mitochondrial DNA repair defects in Ataxia Telangiectasia
    Nilesh K Sharma
    Department of Pharmacology and Physiology, New Jersey Medical School of UMDNJ, 185 South Orange Avenue, Medical Sciences Building, Newark, NJ 07103, United States
    DNA Repair (Amst) 13:22-31. 2014
    b>Ataxia Telangiectasia (A-T) is a progressive childhood disorder characterized most notably by cerebellar degeneration and predisposition to cancer...
  41. doi Characterization of glioma stem cells through multiple stem cell markers and their specific sensitization to double-strand break-inducing agents by pharmacological inhibition of ataxia telangiectasia mutated protein
    Alessandro Raso
    Neurosurgery Unit, Istituto Giannina Gaslini, Genova, Italy
    Brain Pathol 22:677-88. 2012
    ..GSC) may promote radio-resistance by constitutive activation of the DNA damage response started by the ataxia telangiectasia mutated (ATM) protein...
  42. pmc Activation of AMP-activated protein kinase in cerebella of Atm-/- mice is attributable to accumulation of reactive oxygen species
    Xianghong Kuang
    Department of Molecular Carcinogenesis, The University of Texas, MD Anderson Cancer Center, Smithville, TX 78957, United States
    Biochem Biophys Res Commun 418:267-72. 2012
    b>Ataxia telangiectasia (A-T) is an inherited disease, the most prominent feature of which is ataxia caused by degeneration of cerebellar neurons and synapses...
  43. pmc ATM mutations and phenotypes in ataxia-telangiectasia families in the British Isles: expression of mutant ATM and the risk of leukemia, lymphoma, and breast cancer
    T Stankovic
    CRC Institute for Cancer Studies, The Medical School, University of Birmingham, United Kingdom
    Am J Hum Genet 62:334-45. 1998
    ..We also show that 25% of all A-T patients carried in-frame deletions or missense mutations, many of which were also associated with expression of mutant ATM protein...
  44. ncbi The ATM gene and susceptibility to breast cancer: analysis of 38 breast tumors reveals no evidence for mutation
    I Vorechovsky
    Karolinska Institute, Department of Bioscience at Novum, Center for Biotechnology, Huddinge, Sweden
    Cancer Res 56:2726-32. 1996
    ..In addition, because no somatic mutations were found, our study rules out the ATM gene as the frequently altered tumor suppressor gene at 11q23...
  45. doi Antioxidant vitamins intake, ataxia telangiectasia mutated (ATM) genetic polymorphisms, and breast cancer risk
    Sang Ah Lee
    Kangwon National University School of Medicine, Gangwon Do, Korea
    Nutr Cancer 62:1087-94. 2010
    b>Ataxia telangiectasia mutated (ATM) cells exist under a constant state of oxidative stress with high levels of reactive oxygen species, which are removed by cellular antioxidant vitamins...
  46. doi Two brothers with ataxia-telangiectasia-like disorder with lung adenocarcinoma
    Naoki Uchisaka
    Division of Hematology Oncology, Saitama Children s Medical Center, Saitama, Japan
    J Pediatr 155:435-8. 2009
    ..They both had ataxia with cerebellar atrophy and mental retardation. They had the same mutation of the MRE11 gene, which has not been reported previously (c.727T>C and g.24994G>A)...
  47. ncbi Distal spinal muscular atrophy as a major feature in adult-onset ataxia telangiectasia
    J A P Hiel
    Department of Neurology, Maxima Medical Centre, Veldhoven, The Netherlands
    Neurology 67:346-9. 2006
    The authors report four adult-onset ataxia telangiectasia (AT) patients belonging to two families lacking pronounced cerebellar ataxia but displaying distal spinal muscular atrophy...
  48. doi Pathogenic ATM mutations occur rarely in a subset of multiple myeloma patients
    Belinda Austen
    CRUK Institute for Cancer Studies, University of Birmingham, Birmingham, UK
    Br J Haematol 142:925-33. 2008
    b>Ataxia Telangiectasia (A-T) patients have biallelic inactivation of the ATM gene and exhibit a 200-fold-increased frequency of lymphoid tumours...
  49. doi Ataxia telangiectasia: a "disease model" to understand the cerebellar control of vestibular reflexes
    Aasef G Shaikh
    Department of Neurology, Case Western Reserve University, Cleveland, Ohio, USA
    J Neurophysiol 105:3034-41. 2011
    ..In 13 subjects with ataxia telangiectasia (A-T), a disease associated with profound cerebellar cortical degeneration, we found abnormalities of ..
  50. ncbi Cancer in patients with ataxia-telangiectasia and in their relatives in the nordic countries
    J H Olsen
    Institute of Cancer Epidemiology, Danish Cancer Society, Copenhagen, Denmark
    J Natl Cancer Inst 93:121-7. 2001
    ..A population-based study of cancer incidence in A-T families with unbiased selection and tracing of relatives would confirm this hypothesis...
  51. ncbi Adult-onset ataxia telangiectasia due to ATM 5762ins137 mutation homozygosity
    Ian J Sutton
    Queen Elizabeth Neuroscience Centre, Queen Elizabeth Hospital, Edgbaston, Birmingham
    Ann Neurol 55:891-5. 2004
    b>Ataxia telangiectasia (A-T) is an autosomal recessive neurodegenerative disorder that arises because of mutations in the ATM gene...
  52. ncbi Checkpoint abrogation in G2 compromises repair of chromosomal breaks in ataxia telangiectasia cells
    Georgia I Terzoudi
    Institute of Nuclear Technology and Radiation Protection, National Centre for Scientific Research Demokritos, Aghia Paraskevi Attikis, Athens, Greece
    Cancer Res 65:11292-6. 2005
    ..repair of DNA double-strand breaks (DSB) and confers enhanced G(2) chromosomal radiosensitivity in ataxia telangiectasia (AT) cells...
  53. ncbi Ataxia-telangiectasia and the Nijmegen breakage syndrome: related disorders but genes apart
    Y Shiloh
    Department of Human Genetics, Sackler School of Medicine, Tel Aviv University, Israel
    Annu Rev Genet 31:635-62. 1997
    ..The as yet unknown NBS protein may be a component in an ATM-based complex, with a key role in sensing and processing specific DNA damage or intermediates and signaling their presence to the cell cycle machinery...
  54. ncbi Genetic polymorphisms of ataxia telangiectasia mutated affect lung cancer risk
    Jin Hee Kim
    Department of Preventive Medicine, Seoul National University College of Medicine, Republic of Korea
    Hum Mol Genet 15:1181-6. 2006
    The ataxia telangiectasia mutated (ATM) gene is known to be activated by DNA damage and involved in cell cycle arrest, apoptosis and DNA repair...
  55. ncbi Increased oxidative stress in ataxia telangiectasia evidenced by alterations in redox state of brains from Atm-deficient mice
    A Kamsler
    Department of Neurobiochemistry, George S. Wise Faculty of Life Sciences, Tel Aviv University, Israel
    Cancer Res 61:1849-54. 2001
    ..Our findings support the hypothesis that the absence of functional ATM results in oxidative stress, which may be an important cause of the degeneration of cerebellar neurons in A-T...
  56. pmc Degeneration of neurons, synapses, and neuropil and glial activation in a murine Atm knockout model of ataxia-telangiectasia
    R O Kuljis
    Department of Neurology, University of Miami, Miami, FL 33136 2115, USA
    Proc Natl Acad Sci U S A 94:12688-93. 1997
    ....
  57. pmc Ataxia telangiectasia mutated is essential during adult neurogenesis
    D M Allen
    The Salk Institute for Biological Studies, Laboratory of Genetics, La Jolla, California 92037, USA
    Genes Dev 15:554-66. 2001
    b>Ataxia telangiectasia (A-T) is an autosomal recessive disease characterized by normal brain development followed by progressive neurodegeneration...
  58. pmc ATM and ataxia telangiectasia
    Peter J McKinnon
    Department of Genetics and Tumor Cell Biology, St Jude Children s Research Hospital, 332 N Lauderdale, Memphis, Tennessee 38105, USA
    EMBO Rep 5:772-6. 2004
    b>Ataxia telangiectasia (AT) has long intrigued the biomedical research community owing to the spectrum of defects that are characteristic of the disease, including neurodegeneration, immune dysfunction, radiosensitivity and cancer ..
  59. pmc Ataxia telangiectasia gene mutations in leukaemia and lymphoma
    J Boultwood
    Leukaemia Research Fund Molecular Haematology Unit, Nuffield Department of Clinical Laboratory Sciences, John Radcliffe Hospital, Headington, Oxford, OX3 9DU, UK
    J Clin Pathol 54:512-6. 2001
    b>Ataxia telangiectasia (AT) is a rare multisystem, autosomal, recessive disease characterised by neuronal degeneration, genome instability, and an increased risk of cancer...
  60. ncbi Cancer risk in heterozygotes for ataxia-telangiectasia
    B Geoffroy-Perez
    U521 INSERM, Institut Gustave Roussy, 39 rue Camille Desmoulins, 94805 Villejuif Cedex, France
    Int J Cancer 93:288-93. 2001
    ..However, the amplitude of the risk of breast cancer estimated in heterozygous women does not appear to justify a separate screening program from that already available to women with a first-degree relative affected by breast cancer...
  61. ncbi Impaired elimination of DNA double-strand break-containing lymphocytes in ataxia telangiectasia and Nijmegen breakage syndrome
    Paola Porcedda
    Department of Clinical and Biological Sciences, University of Turin, Regione Gonzole 10, 10043 Orbassano, Italy
    DNA Repair (Amst) 5:904-13. 2006
    ..D (ActD), normal quiescent T cells accumulate double-strand breaks and die, whereas T cells from ataxia telangiectasia (AT) and Nijmegen breakage syndrome (NBS) patients are resistant to this death pathway despite a ..
  62. ncbi ATM kinase activity modulates Fas sensitivity through the regulation of FLIP in lymphoid cells
    Venturina Stagni
    Dulbecco Telethon Institute, Department of Experimental Medicine and Biochemical Sciences, University of Rome Tor Vergata, Italy
    Blood 111:829-37. 2008
    b>Ataxia telangiectasia (A-T) is a rare cancer-predisposing genetic disease, caused by the lack of functional ATM kinase, a major actor of the double strand brakes (DSB) DNA-damage response...
  63. doi Coordinated action of the Fanconi anemia and ataxia telangiectasia pathways in response to oxidative damage
    Pau Castillo
    Genome Instability and DNA Repair Group, Department of Genetics and Microbiology, Universitat Autonoma de Barcelona, Spain
    DNA Repair (Amst) 10:518-25. 2011
    Fanconi anemia (FA) and ataxia telangiectasia (AT) share common traits such chromosomal instability and proneness to hematological cancers...
  64. pmc A novel role for ATM in regulating proteasome-mediated protein degradation through suppression of the ISG15 conjugation pathway
    Laurence M Wood
    Department of Microbiology, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America
    PLoS ONE 6:e16422. 2011
    b>Ataxia Telangiectasia (A-T) is an inherited immunodeficiency disorder wherein mutation of the ATM kinase is responsible for the A-T pathogenesis...
  65. pmc Genotype-phenotype relationships in ataxia-telangiectasia and variants
    S Gilad
    Department of Human Genetics, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
    Am J Hum Genet 62:551-61. 1998
    ..We conclude that certain "A-T variant" phenotypes represent ATM mutations, including some of those without telangiectasia. Our findings extend the range of phenotypes associated with ATM mutations...
  66. pmc Mutations associated with variant phenotypes in ataxia-telangiectasia
    C M McConville
    CRC Institute for Cancer Studies, University of Birmingham, United Kingdom
    Am J Hum Genet 59:320-30. 1996
    ..One possibility might be that individuals who are compound heterozygotes for ATM mutations are more common than we realize...
  67. pmc All stressed out without ATM kinase
    J Jefferson P Perry
    Skaggs Institute for Chemical Biology, Department of Molecular Biology, La Jolla, CA 92037, USA
    Sci Signal 4:pe18. 2011
    ..These findings fundamentally affect our understanding of ROS and ATM signaling and of the A-T phenotype, with implications for altering signaling in cancer cells to increase sensitivities to current therapeutic interventions...
  68. ncbi Analysis of the ATM protein in wild-type and ataxia telangiectasia cells
    N D Lakin
    Wellcome Trust Cancer Research Campaign Institute, Cambridge, UK
    Oncogene 13:2707-16. 1996
    b>Ataxia telangiectasia (A-T) is a human disorder that results in a number of clinical symptoms, including cerebellar degeneration and increased cancer predisposition...
  69. ncbi Association of ataxia telangiectasia mutated (ATM) gene mutation/deletion with rhabdomyosarcoma
    Peilin Zhang
    Department of Pathology, West Virginia University Health Sciences Center, Morgontown, West Virginia 26506 9203, USA
    Cancer Biol Ther 2:87-91. 2003
    ..We report here that there is a high frequency of association of rhabdomyosarcoma with ataxia telangiectasia mutated (ATM) gene mutation/deletion...
  70. pmc Immunodeficiency in ataxia telangiectasia is correlated strongly with the presence of two null mutations in the ataxia telangiectasia mutated gene
    E R Staples
    Department of Immunology, Queen s Medical Centre, Nottingham University Hospitals NHS Trust, Nottingham, UK
    Clin Exp Immunol 153:214-20. 2008
    Immunodeficiency affects over half of all patients with ataxia telangiectasia (A-T) and when present can contribute significantly to morbidity and mortality...
  71. ncbi Residual ataxia telangiectasia mutated protein function in cells from ataxia telangiectasia patients, with 5762ins137 and 7271T-->G mutations, showing a less severe phenotype
    G S Stewart
    CRC Institute for Cancer Studies, The University of Birmingham, Vincent Drive, Edgbaston, Birmingham B15 2TT, United Kingdom
    J Biol Chem 276:30133-41. 2001
    We have assessed several ataxia Telangiectasia mutated (ATM)-dependent functions in cells derived from ataxia telangiectasia patients, carrying either an ATM 5762ins137 splice site or a 7271T-->G missense mutation, with a less severe ..
  72. pmc ATM, the Mre11/Rad50/Nbs1 complex, and topoisomerase I are concentrated in the nucleus of Purkinje neurons in the juvenile human brain
    Elena Gorodetsky
    Section on Molecular Neurobiology, Laboratory of Neurogenetics, National Institute on Alcohol Abuse and Alcoholism, 5625 Fishers Lane, Room 3S 32, MSC 9412, Bethesda, MD 20952 9412, USA
    DNA Repair (Amst) 6:1698-707. 2007
    The genetic disease ataxia telangiectasia (AT) results from mutations in the ataxia telangiectasia mutated (ATM) gene. AT patients develop a progressive degeneration of cerebellar Purkinje neurons...
  73. pmc Disease severity in a mouse model of ataxia telangiectasia is modulated by the DNA damage checkpoint gene Hus1
    Gabriel Balmus
    Department of Biomedical Sciences, Cornell University, Ithaca, NY 14853, USA
    Hum Mol Genet 21:3408-20. 2012
    The human genomic instability syndrome ataxia telangiectasia (A-T), caused by mutations in the gene encoding the DNA damage checkpoint kinase ATM, is characterized by multisystem defects including neurodegeneration, immunodeficiency and ..
  74. doi A novel defect in mitochondrial p53 accumulation following DNA damage confers apoptosis resistance in Ataxia Telangiectasia and Nijmegen Breakage Syndrome T-cells
    Valentina Turinetto
    Department of Clinical and Biological Sciences, University of Turin, Orbassano, Italy
    DNA Repair (Amst) 9:1200-8. 2010
    ..accumulation of p53 and apoptosis when treated with the genotoxic agent Actinomycin D (ActD), those from Ataxia Telangiectasia (AT) and Nijmegen Breakage Syndrome (NBS) patients resist ActD-induced apoptosis [1]...
  75. pmc Dexamethasone partially rescues ataxia telangiectasia-mutated (ATM) deficiency in ataxia telangiectasia by promoting a shortened protein variant retaining kinase activity
    Michele Menotta
    Department of Biomolecular Sciences, University of Urbino Carlo Bo, 61029 Urbino, Italy
    J Biol Chem 287:41352-63. 2012
    b>Ataxia telangiectasia (AT) is a rare genetic disease, still incurable, resulting from biallelic mutations in the ataxia telangiectasia-mutated (ATM) gene...
  76. ncbi Single-stranded DNA induces ataxia telangiectasia mutant (ATM)/p53-dependent DNA damage and apoptotic signals
    Alam Nur-E-Kamal
    Department of Pharmacology, Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey, Piscataway, New Jersey 08854, USA
    J Biol Chem 278:12475-81. 2003
    ..Like DNA damaging agents, single-stranded DNA up-regulated p53 and activated the nuclear kinase ataxia telangiectasia mutant (ATM) as evidenced by phosphorylation of histone 2AX, an endogenous ATM substrate...
  77. doi Successful treatment of acute myeloid leukaemia in a patient with ataxia telangiectasia
    Tadashi Onoda
    Department of Paediatrics, Yamagata University Faculty of Medicine, Yamagata, Japan
    Eur J Haematol 91:557-60. 2013
    b>Ataxia telangiectasia (AT) is a rare autosomal recessive multisystem disorder characterised by cerebellar degeneration, immunodeficiency and cancer predisposition...
  78. ncbi A systematic evaluation of the ataxia telangiectasia mutated gene does not show an association with non-Hodgkin lymphoma
    Payal Sipahimalani
    Canada s Michael Smith Genome Sciences Centre, British Columbia Cancer Agency, Vancouver, BC, Canada
    Int J Cancer 121:1967-75. 2007
    The ataxia telangiectasia mutated (ATM) gene is critical for the detection and repair of DNA double-stranded breaks...
  79. ncbi High frequency of spontaneous translocations revealed by FISH in cells from patients with the cancer-prone syndromes ataxia telangiectasia and Nijmegen breakage syndrome
    M Stumm
    Institute of Human Genetics, Otto von Guericke University, Magdeburg, Germany
    Cytogenet Cell Genet 92:186-91. 2001
    ..We have analyzed the frequency of translocations in lymphocytes and lymphoblastoid cell lines from ataxia telangiectasia (AT) and Nijmegen breakage syndrome (NBS) homozygotes and heterozygotes using a three-color chromosome-..
  80. ncbi Ataxia telangiectasia: G2 checkpoint and chromosomal damage in proliferating lymphocytes
    J Pincheira
    , Facultad de Medicina, Universidad de Chile, Santiago, Chile
    Mutagenesis 16:419-22. 2001
    There is a checkpoint pathway in eukaryotic cells that depends on ATM (ataxia telangiectasia mutated) kinase which activates the processes leading to the repair of DNA damage and also lengthens the G(2) stage of the cell cycle...
  81. ncbi Glutathione levels in blood from ataxia telangiectasia patients suggest in vivo adaptive mechanisms to oxidative stress
    Paolo Degan
    Italian National Cancer Institute, IST I 16132 Genoa, Italy
    Clin Biochem 40:666-70. 2007
    To evaluate an in vivo pro-oxidant state in patients with ataxia telangiectasia (AT).
  82. pmc Pulmonary function in children and young adults with ataxia telangiectasia
    Sharon A McGrath-Morrow
    Eudowood Division of Pediatric Respiratory Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland
    Pediatr Pulmonol 49:84-90. 2014
    Pulmonary disease contributes to significant morbidity and mortality in people with ataxia telangiectasia (A-T)...
  83. pmc Survival probability in ataxia telangiectasia
    T O Crawford
    Department of Neurology, The Johns Hopkins Hospital, Baltimore, Maryland 21287, USA
    Arch Dis Child 91:610-1. 2006
    b>Ataxia telangiectasia is a rare, multiorgan neurodegenerative disorder with enhanced vulnerability to cancer and infection...
  84. ncbi Independent mutational events are rare in the ATM gene: haplotype prescreening enhances mutation detection rate
    Midori Mitui
    Department of Pathology and Laboratory Medicine, The David Geffen School of Medicine, Los Angeles, California 90095 1732, USA
    Hum Mutat 22:43-50. 2003
    ..In all, 62 different mutations (28 not previously reported) were identified and their associated haplotypes defined, thereby establishing a new database for Iberian A-T families, and extending the spectrum of worldwide ATM mutations...
  85. ncbi The Ataxia-telangiectasia mutated gene and breast cancer: gene expression profiles and sequence variants
    Janet Hall
    DNA Repair Team, International Agency for Research on Cancer, 150 cours Albert Thomas, 69372 Lyon Cedex, France
    Cancer Lett 227:105-14. 2005
    ..The potential role of such variants needs to be further assessed, together with functional studies to model their impact on ATM function...
  86. ncbi Changes of chromatin condensation in one patient with ataxia telangiectasia disorder: a structural study
    L Vergani
    Institute of Biophysics, School of Medicine, University of Genoa, 16132 Italy
    J Cell Biochem 75:578-86. 1999
    ..characterize the structure and organization of in situ chromatin in lymphoblastoid cells obtained from one ataxia telangiectasia (A-T) patient and one healthy family member...
  87. pmc Lack of ataxia telangiectasia mutated kinase induces structural and functional changes in the heart: role in β-adrenergic receptor-stimulated apoptosis
    CERRONE R FOSTER
    Department of Physiology, James H Quillen College of Medicine, East Tennessee State University, Johnson City, TN 37614, USA
    Exp Physiol 97:506-15. 2012
    b>Ataxia telangiectasia mutated kinase (ATM) is involved in cell cycle checkpoints, DNA repair and apoptosis. β-Adrenergic receptor (β-AR) stimulation induces cardiac myocyte apoptosis...
  88. pmc Radiosensitive melanoma cell line with mutation of the gene for ataxia telangiectasia
    J Ramsay
    Queensland Radium Institute Mater Centre, South Brisbane, Australia
    Br J Cancer 77:11-4. 1998
    ..Using a protein truncation assay, a mutation for the gene for ataxia telangiectasia (ATM) was identified in HT144 cells...
  89. ncbi Ataxia-telangiectasia: founder effect among north African Jews
    S Gilad
    Department of Human Genetics, Sackler School of Medicine, Tel Aviv University, Ramat Aviv, Israel
    Hum Mol Genet 5:2033-7. 1996
    ..This founder effect provides a unique opportunity for population-based screening for A-T carriers in a large Jewish community...
  90. doi Elevated serum IL-8 levels in ataxia telangiectasia
    Sharon A McGrath-Morrow
    Division of Pediatric Pulmonology, The Johns Hopkins Medical Institutions, Baltimore, MD, USA
    J Pediatr 156:682-4.e1. 2010
    Serum interleukin (IL)-8 levels were measured in 50 patients with ataxia telangiectasia (A-T) and 22 without A-T. In a cross-sectional study, the geometric mean of IL-8 level was significantly higher in the patients with A-T (P <...
  91. ncbi Activation and regulation of ATM kinase activity in response to DNA double-strand breaks
    J H Lee
    Department of Molecular Genetics and Microbiology, Institute of Cellular and Molecular Biology, University of Texas at Austin, Austin, TX 78712, USA
    Oncogene 26:7741-8. 2007
    ..We also compare observations of the ATM activation process in different biological systems and highlight potential candidates for cellular factors that may participate in regulating ATM activity in human cells...
  92. ncbi The ATM gene and ataxia telangiectasia
    Ariadni Mavrou
    Department of Medical Genetics, Athens University School of Medicine, Aghia Sofia Childrens Hospital, Thivon and Levadias, 115 27 Athens, Greece
    Anticancer Res 28:401-5. 2008
    b>Ataxia telangiectasia (AT) is a rare neurodegenerative, autosomal recessive disorder characterized by chromosome instability, radiosensitivity, immunodeficiency and a predisposition for cancer...
  93. pmc A high frequency of distinct ATM gene mutations in ataxia-telangiectasia
    J Wright
    Virginia Mason Research Center, Seattle, WA 98101, USA
    Am J Hum Genet 59:839-46. 1996
    ..However, such screening may need to be done prospectively, that is, by searching for new mutations rather than by screening for just those already identified in AT families...
  94. pmc Ataxia telangiectasia mutated kinase controls chronic gammaherpesvirus infection
    Joseph M Kulinski
    Microbiology and Molecular Genetics, Medical College of Wisconsin Blood Research Institute, Blood Center of Wisconsin, Milwaukee, Wisconsin, USA
    J Virol 86:12826-37. 2012
    ....
  95. doi Non invasive assessment of lung disease in ataxia telangiectasia by high-field magnetic resonance imaging
    Silvia Montella
    Department of Translational Medical Sciences, Federico II University, Via Pansini 5, 80131, Naples, Italy
    J Clin Immunol 33:1185-91. 2013
    A sensitive imaging technique that assesses ataxia telangiectasia (AT) lung disease without ionizing radiation is highly desirable...
  96. doi Premature ageing of the immune system underlies immunodeficiency in ataxia telangiectasia
    Andrew Robert Exley
    Immunology Laboratory, Department of Pathology, Papworth Hospital NHS Foundation Trust, Cambridge University Health Partners, Cambridge CB23 3RE, UK
    Clin Immunol 140:26-36. 2011
    ..pathways implicated in premature ageing and ATM genotype predicts survival, yet immunodeficiency in ataxia telangiectasia is regarded as mild and unrelated to age...
  97. ncbi Expression of a dominant negative I kappa B-alpha modulates hypersensitivity of ataxia telangiectasia fibroblasts to streptonigrin-induced apoptosis
    M Jung
    Department of Radiation Medicine, Georgetown University Medical Center, Washington, D C, USA
    Radiat Oncol Investig 5:265-8. 1997
    b>Ataxia telangiectasia (AT) cells exhibit greater levels of apoptosis than normal fibroblasts following exposure to X-rays or radiomimetic drugs...
  98. pmc ISG15 deregulates autophagy in genotoxin-treated ataxia telangiectasia cells
    Shyamal D Desai
    Department of Biochemistry and Molecular Biology, Louisiana State University Health Sciences Center School of Medicine, New Orleans, Louisiana 70112, USA
    J Biol Chem 288:2388-402. 2013
    ..Supporting the model, we show that autophagy is activated in the brain tissues of human A-T patients. This highlights a plausible causal contribution of a novel "ISG15 proteinopathy" in A-T neuronal cell death...
  99. doi Two unrelated patients with MRE11A mutations and Nijmegen breakage syndrome-like severe microcephaly
    Yoshiyuki Matsumoto
    Department of Genetics and Cell Biology, Research Institute for Radiation Biology and Medicine, Hiroshima University, Kasumi 1 2 3, Hiroshima 734 8553, Japan
    DNA Repair (Amst) 10:314-21. 2011
    ..The translationally silent mutation common to both patients had an effect on splicing efficiency resulting in reduced but normal MRE11 protein. Their levels of radiation-induced activation of ATM were higher than those in ATLD cells...
  100. ncbi 'Wasted', a new mutant of the mouse with abnormalities characteristic to ataxia telangiectasia
    L D Shultz
    Nature 297:402-4. 1982
  101. pmc KARP-1 is induced by DNA damage in a p53- and ataxia telangiectasia mutated-dependent fashion
    K Myung
    Department of Molecular Biology, Cell Biology and Biochemistry, Brown University, Providence, RI 02912, USA
    Proc Natl Acad Sci U S A 95:7664-9. 1998
    ..KARP-1 mRNA induction was completely dependent on the ataxia telangiectasia and p53 gene products, consistent with the presence of a p53 binding site within the second intron of the ..

Research Grants69

  1. Molecular mechanisms of lung disease in ataxia telangiectasia
    JoAnn M Sekiguchi; Fiscal Year: 2013
    ..abstract_text> ..
  2. 14th International Workshop on Ataxia-Telangiectasia and ATM
    Richard A Gatti; Fiscal Year: 2010
    ..We also hope to encourage new young investigators to develop an interest in both clinical and basic A-T/ATM-related research. ..
  3. The function of ATM protein in the biology of the adult neuron CNS:
    Karl Herrup; Fiscal Year: 2013
    ..The exploration of these phenomena will thus have significant value for our basic biological understanding of brain function as well as its malfunction in a number of different clinically relevant situations. ..
  4. Chromatin Modifications and Vulnerability to Glutamate Toxicity
    ALEXEI D KONDRATYEV; Fiscal Year: 2010
    ..such as Alzheimer's, Huntington's, and Parkinson's diseases, amyotrophic lateral sclerosis, ataxia telangiectasia and many other neurological disorders...
  5. MECHANISMS OF GASTROINTESTINAL GROWTH AND TRANSFORMATION
    Juanita L Merchant; Fiscal Year: 2013
    ..that the zinc finger transcription factor ZBP-89 interacts directly with the tumor suppressor protein ataxia telangiectasia mutated (ATM) in response to histone deacetylase inhibition (HDACi), e.g...
  6. ATM Controls Genomic Stability in Pluripotent Stem Cells
    JASON MARK BECKTA; Fiscal Year: 2013
    ..Recently, data has arisen demonstrating that the ataxia telangiectasia-mutated (ATM) kinase mediates this checkpoint, conflicting with older reports which posit that ATM has no ..
  7. Development of a Porcine Model of Ataxia-Telangiectasia
    Christopher Rogers; Fiscal Year: 2011
    ..This project is relevant to the NIH's mission because it will provide a resource to stimulate discovery, therapeutic application, and the development of new diagnostic tools. ..
  8. The Role of hPso4 in DNA Repair and Chemotherapy Resistance
    Montaser Shaheen; Fiscal Year: 2013
    ..We will deplete this E2 and evaluate if this will achieve the same chemosensitivity as depleting hPso4. This will open the opportunity to identify Ubc3 small molecule inhibitors as cancer therapy. ..
  9. Development of a Porcine Model of Ataxia-Telangiectasia
    Christopher Rogers; Fiscal Year: 2013
    ....
  10. Cyclin-Dependent Kinase Inhibition During S Phase
    Geoffrey I Shapiro; Fiscal Year: 2013
    ..abstract_text> ..
  11. The Role of PGC-1aplha in the Pathogenesis of Myotonic Dystrophy Type 1
    Xiang Fang; Fiscal Year: 2013
    ..3) aim 3 will explore the mechanism by which expanded CUG repeats cause a redox-dependent activation of Ataxia Telangiectasia- Mutated (ATM) kinase, phosphorylates and alters AMPK activity in DM1...
  12. Recombination Repair Complex in Human Cells
    Richard Fishel; Fiscal Year: 2013
    ..cancers including hereditary breast cancer (BRCA1/2) as well as hematopoietic and other solid tumors (Ataxia telangiectasia mutated, ATM;Nijmegen Breakage syndrome, NBS;Fanconia Anemia, FANC;Bloom's syndrome, BLM), among ..
  13. Targeting the DNA damage response pathway for the treatment of HSV esophagitis
    Oleg Alekseev; Fiscal Year: 2013
    ..activated by HSV-1 is the DNA damage response (DDR), initiated by the phosphorylation of a sensor kinase ataxia telangiectasia mutated (ATM)...
  14. ATM, REACTIVE OXYGEN, AND CELLULAR RESPONSES TO HYPOXIA
    MICHAEL BARRY KASTAN; Fiscal Year: 2013
    ..New insights gained could be beneficial not only to this patient population, but could also benefit patients with cancer, cardiovascular disease, and neurological disorders. ..
  15. Regulation of mTORC1 signaling by mROS and ATM
    BROOKE ELIZABETH CHRISTIAN; Fiscal Year: 2013
    ..The long-term goal of this project is to better understand the role of mROS in ATM and mTORC1 signaling, which may allow development of new therapeutic strategies for A-T. ..
  16. Targeted Degradation of DNA Damage Response Proteins by Autophagy
    Thomas J Begley; Fiscal Year: 2013
    ..We will perform genetic, biochemical and proteomic based experiments in S. cerevisiae to test our hypothesis and to define the molecular signals that allow autophagy to target specific proteins for degradation. ..
  17. Mechanisms of ATM activation
    Tanya T Paull; Fiscal Year: 2013
    ..Greater understanding of the mechanisms of ATM activation is essential for our understanding of the primary cellular defense against genomic instability and tumor progression. ..
  18. Genome maintenance functions of CREB/ATF transcription factors
    RANDAL SCOT TIBBETTS; Fiscal Year: 2013
    ....
  19. Genetic Analysis of Ataxia-telangiectasia
    DAVID WASSARMAN; Fiscal Year: 2012
    ..We have established a Drosophila A-T model that mimics features of neurodegeneration in A-T patients. Using this model we propose to identify gene targets for therapeutic approaches that protect neurons from degeneration in A-T. ..
  20. Tumor-cell-specific targets for combined hyperthermia and radiation effects
    Tej K Pandita; Fiscal Year: 2013
    ..If the proposed research is successfully carried out, the novel information generated from the proposed studies will be useful in designing tumor specific therapies. ..
  21. 15th International Workshop on Ataxia-Telangiectasia and ATM to be held in India
    Tej K Pandita; Fiscal Year: 2012
    ..This will be the first A-T Workshop that provides a forum to discuss the near term potential for applying the results from basic ATM studies to possible A-T clinical treatment trials and, in the future, other neurological diseases. ..
  22. Ataxia Telangiectasia in the CNS - Cause and Effect
    Margot Mayer Proschel; Fiscal Year: 2010
    b>Ataxia Telangiectasia (AT) is a genetic disorder that surprisingly manifests itself only in certain tissues...
  23. ATM and DNA Damage in the Nervous System
    Peter J McKinnon; Fiscal Year: 2013
    ..The neurodegenerative syndrome ataxia telangiectasia (A-T), which results from loss of function of the DNA damage-signaling serine/threonine kinase ATM (ataxia ..
  24. Targeting the DNA Damage Response for the Treatment of Herpes Simplex Labialis
    WILLIAM DONEGAN; Fiscal Year: 2013
    ..HSV-1 activates the ataxia telangiectasia mutated (ATM) sensor kinase, and while the cause of ATM activation in response to HSV- 1 infection is ..
  25. In vivo Analysis of ATM-Regulated Pathways
    RANDAL SCOT TIBBETTS; Fiscal Year: 2011
    ..We are specifically interested in examining whether deregulation of CREB contributes to the manifestation of A-T-related phenotypes, including cancer, and neuron demise. ..
  26. Exploring the role of Mre11 nuclease activity in DNA repair and genome stability
    JEFFREY MICHAEL BUIS; Fiscal Year: 2010
    ..The MRN complex is an early respondent to breaks possibly holding the strands together and signaling ataxia telangiectasia mutated (ATM) kinase...
  27. ATM FUNCTION DURING V(D)J RECOMBINATION
    Barry P Sleckman; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): Mutations in the gene encoding the ATM serine-threonine kinase cause Ataxia Telangiectasia (A-T), a disease marked by lymphopenia and an increased incidence of lymphoid tumors with translocations ..
  28. The Meningioma Consortium: Genome-Wide Association Study
    Elizabeth B Claus; Fiscal Year: 2013
    ..risk with variants in BRIP1 (the breast cancer susceptibility gene (BRCA1)-interacting protein) and ATM (ataxia telangiectasia mutated gene) and 4) Replicate previous associations from the Tineas Capitas study of meningioma risk with ..
  29. ATM as target for malignant glioma radiosensitization.
    KRISTOFFER CARL VALERIE; Fiscal Year: 2013
    ..Thus, more effective treatment is urgently needed. Ataxia telangiectasia (A-T) mutated (ATM) is a critical genome surveillance protein that regulates many DNA damage responses ..
  30. FASEB SRC on Genetic Recombination and Genome Rearrangements
    JOHN HJ PETRINI; Fiscal Year: 2011
    ..The discovery that several human cancer prone syndromes, for example, Ataxia Telangiectasia (A-T), Nijmegen Breakage Syndrome (NBS) and A-T like disorder (A-TLD), are caused by defects in double-..
  31. The Role of ATM in Suppression of Lymphomas
    Shan Zha; Fiscal Year: 2013
    ....
  32. Cooperative roles for Atm and Hus1 in genome maintenance
    Robert Weiss; Fiscal Year: 2009
    ..abstract_text> ..
  33. Caveolin 1: a novel modulator of the PP2A/ATM/p53 pathway
    Ferruccio Galbiati; Fiscal Year: 2013
    ....
  34. Role of the Mre11/Rad50/Nbs1 complex in DNA damage response pathways
    Xiaohua Wu; Fiscal Year: 2012
    ..These studies will ultimately help develop therapeutic interventions for human diseases associated with genome instability and cancer. ..
  35. The role of ATM in glucose transport and insulin signaling in skeletal muscle
    Jonathan S Fisher; Fiscal Year: 2010
    Humans and animals with deficient ataxia telangiectasia mutated (ATM) are insulin-resistant or hyperglycemic. ATM reportedly indirectly influences insulin signaling, including phosphorylation of Akt, in various cell types...
  36. A Novel Pathway Involving ATM, PP1 and I-2
    Sankar Mitra; Fiscal Year: 2012
    ..the molecular mechanism of ATM in DNA damage and repair pathways as an attempt to further understand Ataxia Telangiectasia, an autosomal recessive genetic disease associated with loss-of-function mutations in the ATM gene...
  37. Regulation of the ATM/ATR-p53 DNA Damage Signaling Pathway by the Wip1 Phosphatas
    Xiongbin Lu; Fiscal Year: 2013
    ..The goal of this research project is to (1) clarify the functions of Wip1 in the ATM (Ataxia Telangiectasia Mutated) initiated DNA damage response pathway;(2) determine if inhibiting Wip1 would rescue ATM ..
  38. Roles of Mre11 in lymphocyte development and DNA repair
    David O Ferguson; Fiscal Year: 2013
    ..These diseases include ataxia telangiectasia, ataxia telangiectasia like disorder, and Nijmegen breakage syndrome which can cause immunodeficiency, ..
  39. A novel protein regulating thymocyte development
    NICHOLAS R GASCOIGNE; Fiscal Year: 2010
    ..PLC-gamma) and Itk, both enzymes crucial to early stages in signaling via the TCR, as well as with Ataxia telangiectasia mutated (ATM), a master regulator of cell cycle checkpoints that tests for DNA damage...
  40. ATDC Function in Human Pancreatic Adenocarcinoma
    Diane M Simeone; Fiscal Year: 2011
    ..PUBLIC HEALTH RELEVANCE: We propose that ATDC is a promising novel therapeutic target in pancreatic cancer because it's inactivation may lead to both reduced tumor growth and sensitization to chemotherapy. ..
  41. Neuroprotective drugs for A-T
    DAVID WASSARMAN; Fiscal Year: 2013
    ....
  42. Regulation of the ATR Checkpoint Kinase by DNA Damage
    Lee Zou; Fiscal Year: 2013
    ..These studies may significantly advance the current model of ATR activation, providing the molecular basis for future studies to reveal the full biological functions of ATR and its implications in targeted cancer therapy. ..
  43. Mechanisms of Mitotic Activation of the ATM kinase
    Sankar Mitra; Fiscal Year: 2013
    ..Dissecting the important role of ATM in mitosis may help understand many A-T phenotypes and find a cure for the disease. ..
  44. Identification of Novel Protein Phosphatases in the ATM Signaling Pathway
    Xiongbin Lu; Fiscal Year: 2010
    ..The goal of this research project is to (1) clarify the functions of protein phosphatases in the ATM (Ataxia Telangiectasia Mutated) initiated DNA damage response pathway;(2) determine how protein phosphatases regulate DNA damage-..
  45. Glial Dysfunction in Ataxia Telangiectasia
    Margot Mayer Proschel; Fiscal Year: 2009
    ..on defining and characterizing a potentially novel cellular target that is affected in the genetic disease Ataxia telangiectasia (AT)...
  46. Themis Regulation of Thymocyte Selection
    NICHOLAS R GASCOIGNE; Fiscal Year: 2011
    ..The important phosphorylation sites in Themis will be identified, and interactions with particular binding partners including the kinases Itk and ataxia telangiectasia mutated (ATM) will be dissected.
  47. Coordination of Respiration with Deglutition & Phonation in Ataxia-Telangiectasia
    Maureen Lefton Greif; Fiscal Year: 2007
    ..Furthermore, developing A- T as a model will form the basis for applying this non-invasive technology to other children with dysphagia. [unreadable] [unreadable] [unreadable]..
  48. Function & Purification of the Fanconi Anemia Protein C*
    Gary Kupfer; Fiscal Year: 2006
    ..wide applicability in science in general and cancer in particular, such as Li- Fraument syndrome (p53), ataxia telangiectasia (P13 kinase), and xeroderma pigmentosum (DNA nucleotide excision repair)...
  49. RISK OF CANCER IN A-T FAMILIES
    Robert Haile; Fiscal Year: 2003
    ..We propose no new mutation screening in the current proposal. We believe this is a scientifically defensible compromise and hope that it will allow us to begin this important study. ..
  50. Role of ATM in Cardiac Myocyte Loss and Myocardial Remodeling
    Krishna Singh; Fiscal Year: 2009
    b>Ataxia telangiectasia (A-T) results from mutation of the ATM gene. Individuals with an ATM mutation in one allele are spared from most of the symptoms of the disease, but are more susceptible to cancer and ischemic heart disease...
  51. Biology of CHK2 Kinase In Lung Cancer
    Weixin Wang; Fiscal Year: 2005
    ..This DNA damage signaling pathway is initiated by ATM kinase, a gene mutated in a rare genetic disease ataxia telangiectasia (AT)...
  52. PROBING THE DNA DAMAGE RESPONSE IN VITRO
    Jean Gautier; Fiscal Year: 2006
    ..These studies will provide valuable information on how the DNA damage response can be impaired or lost in the case of cancer and will help identify drugs that influence the DNA damage response. ..
  53. Regulation of non-histone protein functions by histone deacetylases
    Edward Seto; Fiscal Year: 2010
    ..b>Ataxia telangiectasia (AT) is a rare, autosomal recessive, progressive, neurodegenerative childhood disease that affects the ..
  54. ATM and ATR in Chromium-Induced S-Phase Arrest
    Bo Xu; Fiscal Year: 2005
    ....
  55. DNA STRAND BREAKS AND THE GENETIC BASIS OF LYMPHOMAS
    Gilbert Chu; Fiscal Year: 2001
    ..The signal for cell cycle arrest requires the ATM and p53 genes, which are mutated in at ataxia telangiectasia and Li-Fraumeni syndrome...
  56. G2 CHECKPOINT FUNCTION IN HUMAN FIBROBLASTS
    William Kaufmann; Fiscal Year: 2007
    ..b>Ataxia telangiectasia-mutated (ATM) and BRCA1 are required for effective DNA damage G2 checkpoint function...
  57. Antioxidant Therapy for Ataxia Telangiectasia
    ROBERT SCHIESTL; Fiscal Year: 2009
    ATM (ataxia telangiectasia mutated) heterozygosity seems to be a risk factor for cancer...
  58. Defining a Role for ATM in the Nervous System
    Carrolee Barlow; Fiscal Year: 2004
    ..However, in many other instances the molecular mechanism is not clear. Ataxia Telangiectasia (A-T) is one such disease...
  59. Chromatin remodeling specific interactions of ATM
    Sundaresan Venkatachalam; Fiscal Year: 2009
    ..Determining the role of ATM in modulating chromatin remodeling will allow us to formulate therapeutic approaches aimed at affecting chromatin remodeling in AT patients in the future. ..
  60. Deregulation of the Ubiquitin/26S Proteasome Pathway in AT cells: Role of ISG15
    SHYAMAL DESAI; Fiscal Year: 2009
    b>Ataxia Telangiectasia (A-T) (Boder-Sedgwick/Louis-Bar syndrome) is an inherited immunodeficiency disorder with a prevalence of 1 in 30,000-100,000 births...
  61. FUNCTION OF THE ATAXIA TELANGIECTASIA GENE PRODUCT
    Lewis Cantley; Fiscal Year: 2002
    b>Ataxia Telangiectasia (A-T) is an autosomal recessive, pleiotrophic human disorder characterized by progressive neurodegenerative cerebellar ataxia, radiosensitivity, immunodeficiencies, telangiectases of eyes and skin, a greatly ..
  62. Role of ATM in Radiosensitivity of Gliomas
    Chandan Guha; Fiscal Year: 2004
    ..IV) To investigate the combined toxicity of the virus vectors, ATM attenuation and radiation therapy in cultured endothelial cells, astrocytes, oligodendrocytes, neurons and brain tissues in mice models. ..
  63. CELLULAR RESPONSES TO UV LIGHT IN ATAXIA TELANGIECTASIA
    Kathleen Dixon; Fiscal Year: 2007
    ..This improved understanding may ultimately lead to the development of strategies for preventing and/or treating diseases that are characterized by genomic instability and neurological defects. ..
  64. COMPLEMENTATION OF THE NIJMEGEN BREAKAGE SYNDROME DEFECT
    CORDULA KIRCHGESSNER; Fiscal Year: 1999
    ..Patients affected by NBS do not display cerebellar ataxia or telangiectasia, two prominent symptoms in Ataxia telangiectasia patients...
  65. ENZYMATIC MECHANISMS OF GENETIC RECOMBINATION
    Richard Kolodner; Fiscal Year: 2001
    ..recombination and cell lines derived from individuals with Blooms syndrome and other diseases like ataxia telangiectasia appear to have elevated levels of recombination...
  66. Y vh 1 p: phosphatase inhibitor of telomere signaling
    Rolf Craven; Fiscal Year: 2003
    ..Meclp is related to the human Atm (Ataxia telangiectasia mutated) tumor suppressor protein, and phenotypes detected in mecl cells are similar to those found in ..
  67. Role of 53BP1 during the DNA damage response
    PHILLIP CARPENTER; Fiscal Year: 2006
    ..molecular defects in various DNA damage-response/cell cycle checkpoint genes including ATM (mutated in ataxia telangiectasia), BRCA1 (Breast cancer gene 1), p53, NBS1, and CHK2...
  68. DNA Damage Responses in B Cell Development
    John P Manis; Fiscal Year: 2010
    ..These findings may lead to the development of novel and rational therapeutic targets for cancer in patients with AT. ..
  69. Expression profiling from microdissected samples
    Marianna Goldrick; Fiscal Year: 2004
    ..as models of human neurodegenative disorders, including Alzheimer's disease, Huntington's disease, and ataxia telangiectasia. The product will be targeted to researchers carrying out expression profiling studies that aim to ..