Y Shiloh

Summary

Affiliation: Tel Aviv University
Country: Israel

Publications

  1. ncbi request reprint 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
  2. ncbi request reprint ATM-mediated response to DNA double strand breaks in human neurons derived from stem cells
    Sharon Biton
    David and Inez Myers Laboratory for Genetic Research, Department of Molecular Genetics and Biochemistry, Sackler School of Medicine, Tel Aviv University, Tel Aviv 69978, Israel
    DNA Repair (Amst) 6:128-34. 2007
  3. ncbi request reprint Inhibition of transforming growth factor-beta1 signaling attenuates ataxia telangiectasia mutated activity in response to genotoxic stress
    Julia Kirshner
    Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, California, USA
    Cancer Res 66:10861-9. 2006
  4. pmc Differential roles of ATM- and Chk2-mediated phosphorylations of Hdmx in response to DNA damage
    Yaron Pereg
    Department of Molecular Genetics and Biochemistry, Sackler School of Medicine, Tel Aviv University, Tel Aviv 69978, Israel
    Mol Cell Biol 26:6819-31. 2006
  5. ncbi request reprint Chromatin relaxation in response to DNA double-strand breaks is modulated by a novel ATM- and KAP-1 dependent pathway
    Yael Ziv
    The David and Inez Myers Laboratory for Genetic Research, Department of Molecular Genetics and Biochemistry, Sackler School of Medicine, Tel Aviv University, Tel Aviv 69978, Israel
    Nat Cell Biol 8:870-6. 2006
  6. ncbi request reprint Analysis of the ataxia telangiectasia mutated-mediated DNA damage response in murine cerebellar neurons
    Inbal Dar
    Department of Neurobiochemistry, George S Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv 69978, Israel
    J Neurosci 26:7767-74. 2006
  7. pmc Condensin I recruitment and uneven chromatin condensation precede mitotic cell death in response to DNA damage
    Michael Blank
    The David and Inez Myers Laboratory for Genetic Research, Department of Molecular Genetics and Biochemistry, and Interdepartmental Core Facility, Sackler School of Medicine, Tel Aviv University, Tel Aviv 69978, Israel
    J Cell Biol 174:195-206. 2006
  8. ncbi request reprint The ATM-mediated DNA-damage response: taking shape
    Yosef Shiloh
    The David and Inez Myers Laboratory for Genetic Research, Department of Molecular Genetics and Biochemistry, Sackler School of Medicine, Tel Aviv University, Tel Aviv 69978, Israel
    Trends Biochem Sci 31:402-10. 2006
  9. ncbi request reprint Nuclear ataxia-telangiectasia mutated (ATM) mediates the cellular response to DNA double strand breaks in human neuron-like cells
    Sharon Biton
    The David and Inez Myers Laboratory for Genetic Research, Department of Molecular Genetics and Biochemistry, Tel Aviv University, Tel Aviv 69978, Israel
    J Biol Chem 281:17482-91. 2006
  10. ncbi request reprint Ataxia telangiectasia mutated (ATM) is essential for DNA-PKcs phosphorylations at the Thr-2609 cluster upon DNA double strand break
    Benjamin P C Chen
    Division of Molecular Radiation Biology, Department of Radiation Oncology, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas 75390, USA
    J Biol Chem 282:6582-7. 2007

Research Grants

Collaborators

Detail Information

Publications41

  1. ncbi request reprint 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...
  2. ncbi request reprint ATM-mediated response to DNA double strand breaks in human neurons derived from stem cells
    Sharon Biton
    David and Inez Myers Laboratory for Genetic Research, Department of Molecular Genetics and Biochemistry, Sackler School of Medicine, Tel Aviv University, Tel Aviv 69978, Israel
    DNA Repair (Amst) 6:128-34. 2007
    ..We present here unique and powerful model systems to further study the ATM-mediated network in neurons...
  3. ncbi request reprint Inhibition of transforming growth factor-beta1 signaling attenuates ataxia telangiectasia mutated activity in response to genotoxic stress
    Julia Kirshner
    Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, California, USA
    Cancer Res 66:10861-9. 2006
    ....
  4. pmc Differential roles of ATM- and Chk2-mediated phosphorylations of Hdmx in response to DNA damage
    Yaron Pereg
    Department of Molecular Genetics and Biochemistry, Sackler School of Medicine, Tel Aviv University, Tel Aviv 69978, Israel
    Mol Cell Biol 26:6819-31. 2006
    ..These results demonstrate a sophisticated control by ATM of a target protein, Hdmx, which itself is one of several ATM targets in the ATM-p53 axis of the DNA damage response...
  5. ncbi request reprint Chromatin relaxation in response to DNA double-strand breaks is modulated by a novel ATM- and KAP-1 dependent pathway
    Yael Ziv
    The David and Inez Myers Laboratory for Genetic Research, Department of Molecular Genetics and Biochemistry, Sackler School of Medicine, Tel Aviv University, Tel Aviv 69978, Israel
    Nat Cell Biol 8:870-6. 2006
    ..These results suggest that chromatin relaxation is a fundamental pathway in the DNA-damage response and identify its primary mediators...
  6. ncbi request reprint Analysis of the ataxia telangiectasia mutated-mediated DNA damage response in murine cerebellar neurons
    Inbal Dar
    Department of Neurobiochemistry, George S Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv 69978, Israel
    J Neurosci 26:7767-74. 2006
    ..These results support the notion that the cerebellar degeneration in A-T patients results from defective DNA damage response...
  7. pmc Condensin I recruitment and uneven chromatin condensation precede mitotic cell death in response to DNA damage
    Michael Blank
    The David and Inez Myers Laboratory for Genetic Research, Department of Molecular Genetics and Biochemistry, and Interdepartmental Core Facility, Sackler School of Medicine, Tel Aviv University, Tel Aviv 69978, Israel
    J Cell Biol 174:195-206. 2006
    ....
  8. ncbi request reprint The ATM-mediated DNA-damage response: taking shape
    Yosef Shiloh
    The David and Inez Myers Laboratory for Genetic Research, Department of Molecular Genetics and Biochemistry, Sackler School of Medicine, Tel Aviv University, Tel Aviv 69978, Israel
    Trends Biochem Sci 31:402-10. 2006
    ..Genetic, biochemical and structural studies have recently provided insights into the ATM-mediated DSB response, reshaping our view of this signaling pathway while raising new questions...
  9. ncbi request reprint Nuclear ataxia-telangiectasia mutated (ATM) mediates the cellular response to DNA double strand breaks in human neuron-like cells
    Sharon Biton
    The David and Inez Myers Laboratory for Genetic Research, Department of Molecular Genetics and Biochemistry, Tel Aviv University, Tel Aviv 69978, Israel
    J Biol Chem 281:17482-91. 2006
    ..We concluded that nuclear ATM mediates the DSB response in NLCs similarly to in proliferating cells. Attempts to understand the neurodegeneration in A-T should be directed to investigating the DSB response in the nervous system...
  10. ncbi request reprint Ataxia telangiectasia mutated (ATM) is essential for DNA-PKcs phosphorylations at the Thr-2609 cluster upon DNA double strand break
    Benjamin P C Chen
    Division of Molecular Radiation Biology, Department of Radiation Oncology, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas 75390, USA
    J Biol Chem 282:6582-7. 2007
    ..Finally, our result provides a possible mechanism for the direct involvement of ATM in non-homologous end joining-mediated DSB repair...
  11. ncbi request reprint ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage
    Shuhei Matsuoka
    Department of Genetics and Center for Genetics and Genomics, Brigham and Women s Hospital, Howard Hughes Medical Institute, Harvard Medical School, Boston, MA 02115, USA
    Science 316:1160-6. 2007
    ..This database paints a much broader landscape for the DDR than was previously appreciated and opens new avenues of investigation into the responses to DNA damage in mammals...
  12. pmc The histone H2B-specific ubiquitin ligase RNF20/hBRE1 acts as a putative tumor suppressor through selective regulation of gene expression
    Efrat Shema
    Department of Molecular Cell Biology, The Weizmann Institute of Science, Rehovot 76100, Israel
    Genes Dev 22:2664-76. 2008
    ..Furthermore, frequent RNF20 promoter hypermethylation was observed in tumors. RNF20 may thus be a putative tumor suppressor, acting through selective regulation of a distinct subset of genes...
  13. doi request reprint ATM signaling facilitates repair of DNA double-strand breaks associated with heterochromatin
    Aaron A Goodarzi
    Genome Damage and Stability Centre, University of Sussex, East Sussex BN1 9RQ, UK
    Mol Cell 31:167-77. 2008
    ..These data suggest that the importance of ATM signaling for DSB repair increases as the heterochromatic component of a genome expands...
  14. doi request reprint 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...
  15. doi request reprint 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...
  16. pmc SPIKE--a database, visualization and analysis tool of cellular signaling pathways
    Ran Elkon
    The David and Inez Myers Laboratory for Genetic Research, Department of Molecular Genetics and Biochemistry, Sackler School of Medicine, Tel Aviv University, Tel Aviv 69978, Israel
    BMC Bioinformatics 9:110. 2008
    ..The assimilation, visualization and interpretation of these data have become a major challenge in biological research, and once met, will greatly boost our ability to understand cell functioning on a systems level...
  17. ncbi request reprint MRI evidence of white matter damage in a mouse model of Nijmegen breakage syndrome
    Yaniv Assaf
    Department of Neurobiochemistry, George S Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel
    Exp Neurol 209:181-91. 2008
    ..Myelin index and protein levels were significantly reduced in these brains. Our results point to a novel function of Nbs1 in the development and organization of the white matter...
  18. pmc Functional genomic delineation of TLR-induced transcriptional networks
    Ran Elkon
    The David and Inez Myers Laboratory for Genetic Research, Department of Molecular Genetics and Biochemistry, Sackler School of Medicine, Tel Aviv University, Tel Aviv 69978, Israel
    BMC Genomics 8:394. 2007
    ..We sought global delineation of transcriptional networks induced by TLRs, analyzing four genome-wide expression datasets in mouse and human macrophages stimulated with pathogen-mimetic agents that engage various TLRs...
  19. ncbi request reprint Ataxia-telangiectasia: mild neurological presentation despite null ATM mutation and severe cellular phenotype
    Neora Alterman
    The David and Inez Myers Laboratory for Genetic Research, Department of Human Molecular Genetics and Biochemistry, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
    Am J Med Genet A 143:1827-34. 2007
    ..This analysis shows that the severity of the neurological component of A-T is determined not only by ATM mutations but also by other influences yet to be found...
  20. pmc DNA damage-induced phosphorylation of MdmX at serine 367 activates p53 by targeting MdmX for Mdm2-dependent degradation
    Koji Okamoto
    Radiobiology Division, National Cancer Center Research Institute, Tsukiji 5 1 1, Chuo Ku, Tokyo 104 0045, Japan
    Mol Cell Biol 25:9608-20. 2005
    ..We propose that Mdmx phosphorylation at S367 plays an important role in p53 activation after DNA damage by triggering Mdm2-dependent degradation of Mdmx...
  21. pmc EXPANDER--an integrative program suite for microarray data analysis
    Ron Shamir
    School of Computer Science, Sackler Faculty of Exact Sciences, Tel Aviv University, Tel Aviv 69978, Israel
    BMC Bioinformatics 6:232. 2005
    ..Of special need are integrative packages that provide biologist users with advanced but yet easy to use, set of algorithms, together covering the whole range of steps in microarray data analysis...
  22. ncbi request reprint Impaired genomic stability and increased oxidative stress exacerbate different features of Ataxia-telangiectasia
    Shelly Ziv
    Department of Neurobiochemistry, George S Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv 69978, Israel
    Hum Mol Genet 14:2929-43. 2005
    ....
  23. pmc Genome-wide in silico identification of transcriptional regulators controlling the cell cycle in human cells
    Ran Elkon
    The David and Inez Myers Laboratory for Genetic Research, Department of Human Genetics, Sackler School of Medicine, and School of Computer Science, Tel Aviv University, Tel Aviv 69978, Israel
    Genome Res 13:773-80. 2003
    ..The methods presented here are general and can be applied to the analysis of transcriptional networks controlling any biological process...
  24. ncbi request reprint ATM: ready, set, go
    Yosef Shiloh
    The Dovid and Inez Myers Laboratory lor Genetic Research, Department of Human Genetics and Molecular Medicine, Sackler School of Medicine, Tel Aviv University, Tel Aviv 69978, Israel
    Cell Cycle 2:116-7. 2003
  25. ncbi request reprint 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...
  26. ncbi request reprint 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...
  27. ncbi request reprint Contribution of the Atm protein to maintaining cellular homeostasis evidenced by continuous activation of the AP-1 pathway in Atm-deficient brains
    Nir Weizman
    Department of Neurobiochemistry, George S Wise Faculty of Life Sciences, Sackler School of Medicine, Tel Aviv University, Tel Aviv 69978 Israel
    J Biol Chem 278:6741-7. 2003
    ..Our results further demonstrate that inactivation of the ATM gene results in a state of constant stress...
  28. pmc Ionizing radiation induces ataxia telangiectasia mutated kinase (ATM)-mediated phosphorylation of LKB1/STK11 at Thr-366
    Gopal P Sapkota
    MRC Protein Phosphorylation Unit, MSI WTB complex, University of Dundee, Dow Street, Dundee DD1 5EH, Scotland, U K
    Biochem J 368:507-16. 2002
    ..These observations provide the first link between ATM and LKB1 and suggest that ATM could regulate LKB1...
  29. ncbi request reprint Ubiquitination capabilities in response to neocarzinostatin and H(2)O(2) stress in cell lines from patients with ataxia-telangiectasia
    Allen Taylor
    JM USDA Human Nutrition Research Center on Aging at Tufts University, Laboratory for Nutrition and Vision Research, 711 Washington Street, Boston, Massachusetts 02111, USA
    Oncogene 21:4363-73. 2002
    ..The data also add support to the impression that potentiated ubiquitination response to mild oxidative stress is a generalizable phenomenon...
  30. ncbi request reprint ATM-dependent activation of the gene encoding MAP kinase phosphatase 5 by radiomimetic DNA damage
    Anat Bar-Shira
    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
    Oncogene 21:849-55. 2002
    ..Thus, ATM modulates this cycle in response to DSBs. These results further highlight ATM as a link between the DNA damage response and major signaling pathways involved in proliferative and apoptotic processes...
  31. pmc Requirement of the MRN complex for ATM activation by DNA damage
    Tamar Uziel
    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
    EMBO J 22:5612-21. 2003
    ..Collectively, these and previous results assign to components of the MRN complex roles upstream and downstream of ATM in the DNA damage response pathway and explain the clinical resemblance between A-T and A-TLD...
  32. ncbi request reprint PIVOT: protein interacions visualizatiOn tool
    Nir Orlev
    Department of Human Genetics, Faculty of Medicine, Tel Aviv University, Israel
    Bioinformatics 20:424-5. 2004
    ..The user can also employ PIVOT to predict unknown interactions among proteins, based on interactions among their homologous proteins in other species...
  33. ncbi request reprint ATM-mediated phosphorylations inhibit Mdmx/Mdm2 stabilization by HAUSP in favor of p53 activation
    Erik Meulmeester
    Department of Molecular and Cell Biology, Leiden University Medical Center, Leiden, The Netherlands
    Cell Cycle 4:1166-70. 2005
    ..Further insight into the mechanism by which ATM switches the interactions between HAUSP, Mdmx, Mdm2 and p53, to favor p53 activation may offer new tools for therapeutic intervention in the p53 pathway for cancer treatment...
  34. pmc ATM-dependent phosphorylation of ATF2 is required for the DNA damage response
    Anindita Bhoumik
    Signal Transduction Program, The Burnham Institute, La Jolla, California 92037, USA
    Mol Cell 18:577-87. 2005
    ..ATF2 requires neither JNK/p38 nor its DNA binding domain for recruitment to IRIF and the S phase checkpoint. Our findings identify a role for ATF2 in the DNA damage response that is uncoupled from its transcriptional activity...
  35. pmc Dissection of a DNA-damage-induced transcriptional network using a combination of microarrays, RNA interference and computational promoter analysis
    Ran Elkon
    The David and Inez Myers Laboratory for Genetic Research, Department of Human Genetics, Sackler School of Medicine, Tel Aviv University, Tel Aviv, 69978, Israel
    Genome Biol 6:R43. 2005
    ....
  36. pmc Phosphorylation of Hdmx mediates its Hdm2- and ATM-dependent degradation in response to DNA damage
    Yaron Pereg
    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
    Proc Natl Acad Sci U S A 102:5056-61. 2005
    ..These results demonstrate a sophisticated mechanism whereby ATM fine-tunes the optimal activation of p53 by simultaneously modifying each player in the process...
  37. ncbi request reprint Maintaining 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 Cell Biol 6:923-8. 2004
    ..Current progress in this rapidly expanding field was the subject of an EMBO workshop, Maintenance of Genomic Integrity, that took place in June 2004 in Galway, Ireland. Top..
  38. ncbi request reprint In search of drug treatment for genetic defects in the DNA damage response: the example of ataxia-telangiectasia
    Yosef Shiloh
    Department of Human Genetics and Molecular Medicine, Sackler School of Medicine, Tel Aviv University, Tel Aviv 69978, Israel
    Semin Cancer Biol 14:295-305. 2004
    ..This article describes a high throughput strategy for drug screening for A-T that is based on the above principles. A similar strategy can potentially be applied to drug screening for other genetic disorders...
  39. ncbi request reprint Accumulation of DNA damage and reduced levels of nicotine adenine dinucleotide in the brains of Atm-deficient mice
    Nora Stern
    Department of Neurobiochemistry, George S Wise Faculty of Life Sciences, Sackler School of Medicine, Tel Aviv University, Tel Aviv 69978, Israel
    J Biol Chem 277:602-8. 2002
    ..Taken together, our findings support the hypothesis that absence of functional ATM results in continuous stress, which may be an important cause of the degeneration of cerebellar neurons in A-T...
  40. pmc In silico identification of transcriptional regulators associated with c-Myc
    Ran Elkon
    The David and Inez Myers Laboratory for Genetic Research, Department of Human Genetics, Sackler School of Medicine, Tel Aviv University, Israel
    Nucleic Acids Res 32:4955-61. 2004
    ..The approach applied here is general and demonstrates how computational analysis of functional genomics experiments can identify novel modules in complex networks of transcriptional regulation...
  41. ncbi request reprint Deciphering transcriptional regulatory elements that encode specific cell cycle phasing by comparative genomics analysis
    Chaim Linhart
    School of Computer Science, Tel Aviv University, Tel Aviv, Israel
    Cell Cycle 4:1788-97. 2005
    ..Our results reveal novel modules that determine specific cell cycle phasing, and identify their respective putative target genes with remarkably high specificity...

Research Grants13

  1. ATAXIA TELANGIECTASIA--FROM GENE BACK TO PHENOTYPE
    Yosef Shiloh; Fiscal Year: 1999
    ....
  2. ATAXIA-TELANGIECTASIS: FROM GENE BACK TO PHENOTYPE
    Yosef Shiloh; Fiscal Year: 2005
    ..Since Ataxia-telangiectasia is a multisystem disease, understanding its physiological basis is expected to have broad ramifications in various areas of medicine. ..