DNA-PKcs

Summary

Gene Symbol: DNA-PKcs
Description: protein kinase, DNA-activated, catalytic polypeptide
Alias: DNA-PKcs, DNAPK, DNPK1, HYRC, HYRC1, IMD26, XRCC7, p350, DNA-dependent protein kinase catalytic subunit, DNA-PK catalytic subunit, hyper-radiosensitivity of murine scid mutation, complementing 1, p460
Species: human

Top Publications

  1. ncbi CPP32/Yama/apopain cleaves the catalytic component of DNA-dependent protein kinase in the holoenzyme
    H Teraoka
    Department of Pathological Biochemistry, Tokyo Medical and Dental University, Japan
    FEBS Lett 393:1-6. 1996
  2. ncbi Purification and characterization of the double-stranded DNA-activated protein kinase, DNA-PK, from human placenta
    D W Chan
    Department of Biological Sciences, University of Calgary, Canada
    Biochem Cell Biol 74:67-73. 1996
  3. ncbi Cell cycle dependence of DNA-dependent protein kinase phosphorylation in response to DNA double strand breaks
    Benjamin P C Chen
    Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, Texas 75390 9187, USA
    J Biol Chem 280:14709-15. 2005
  4. pmc Phosphorylation in the serine/threonine 2609-2647 cluster promotes but is not essential for DNA-dependent protein kinase-mediated nonhomologous end joining in human whole-cell extracts
    Lawrence F Povirk
    Department of Pharmacology and Toxicology, Massey Cancer Center, Virginia Commonwealth University, Richmond, VA 23298, USA
    Nucleic Acids Res 35:3869-78. 2007
  5. doi HIV-1 causes CD4 cell death through DNA-dependent protein kinase during viral integration
    Arik Cooper
    Virology Laboratory, Vaccine Research Center, National Institute for Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892 3005, USA
    Nature 498:376-9. 2013
  6. pmc The death-associated protein DAXX is a novel histone chaperone involved in the replication-independent deposition of H3.3
    Pascal Drané
    IGMBC Institut de Génétique et de Biologie Moléculaire et Cellulaire, Illkirch F 67400, France
    Genes Dev 24:1253-65. 2010
  7. ncbi 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
  8. pmc Artemis C-terminal region facilitates V(D)J recombination through its interactions with DNA Ligase IV and DNA-PKcs
    Shruti Malu
    Immunology Institute, Mount Sinai School of Medicine, New York, NY 10029, USA
    J Exp Med 209:955-63. 2012
  9. pmc Mismatch-repair protein MSH6 is associated with Ku70 and regulates DNA double-strand break repair
    Ankita Shahi
    DNA Repair Research Center, Department of Pharmacology, Chosun University School of Medicine, 375 Seosuk dong, Gwangju, 501 759, South Korea
    Nucleic Acids Res 39:2130-43. 2011
  10. ncbi Conserved modes of recruitment of ATM, ATR and DNA-PKcs to sites of DNA damage
    Jacob Falck
    The Wellcome Trust and Cancer Research UK Gurdon Institute, and Department of Zoology, Cambridge University, Tennis Court Road, Cambridge CB2 1QN, UK
    Nature 434:605-11. 2005

Research Grants

  1. Lauren Endres; Fiscal Year: 2014
  2. Sandeep Burma; Fiscal Year: 2015
  3. Jianming Qiu; Fiscal Year: 2016
  4. Thomas M Aune; Fiscal Year: 2014
  5. Scanning Correlation Microscopy Methods for Quantifying DNA Repair Kinetics
    Georgios Alexandrakis; Fiscal Year: 2012
  6. CryoEM Structural Studies of DNA-PKcs and Nonhomologous End Joining Complexes
    Phoebe L Stewart; Fiscal Year: 2013
  7. JEREMY MICHAEL STARK; Fiscal Year: 2016
  8. David J Chen; Fiscal Year: 2016
  9. Jean Gautier; Fiscal Year: 2015
  10. Benjamin Ping Chi Chen; Fiscal Year: 2016

Detail Information

Publications228 found, 100 shown here

  1. ncbi CPP32/Yama/apopain cleaves the catalytic component of DNA-dependent protein kinase in the holoenzyme
    H Teraoka
    Department of Pathological Biochemistry, Tokyo Medical and Dental University, Japan
    FEBS Lett 393:1-6. 1996
    DNA-dependent protein kinase (DNA-PK) is composed of a 460-kDa catalytic component (p460) and a DNA-binding component Ku protein...
  2. ncbi Purification and characterization of the double-stranded DNA-activated protein kinase, DNA-PK, from human placenta
    D W Chan
    Department of Biological Sciences, University of Calgary, Canada
    Biochem Cell Biol 74:67-73. 1996
    ..protein kinase (DNA-PK) is a serine-threonine protein kinase that is composed of a large catalytic subunit (p350) and a DNA-binding protein of 70 and 80 kDa subunits known as the Ku autoantigen...
  3. ncbi Cell cycle dependence of DNA-dependent protein kinase phosphorylation in response to DNA double strand breaks
    Benjamin P C Chen
    Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, Texas 75390 9187, USA
    J Biol Chem 280:14709-15. 2005
    ..These results indicate that although IR-induced DNA-PKcs phosphorylation is attenuated in the S phase, DNA-PKcs is preferentially activated by the physiologically relevant DNA replication-associated DSBs at the sites of DNA synthesis...
  4. pmc Phosphorylation in the serine/threonine 2609-2647 cluster promotes but is not essential for DNA-dependent protein kinase-mediated nonhomologous end joining in human whole-cell extracts
    Lawrence F Povirk
    Department of Pharmacology and Toxicology, Massey Cancer Center, Virginia Commonwealth University, Richmond, VA 23298, USA
    Nucleic Acids Res 35:3869-78. 2007
    ....
  5. doi HIV-1 causes CD4 cell death through DNA-dependent protein kinase during viral integration
    Arik Cooper
    Virology Laboratory, Vaccine Research Center, National Institute for Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892 3005, USA
    Nature 498:376-9. 2013
    ....
  6. pmc The death-associated protein DAXX is a novel histone chaperone involved in the replication-independent deposition of H3.3
    Pascal Drané
    IGMBC Institut de Génétique et de Biologie Moléculaire et Cellulaire, Illkirch F 67400, France
    Genes Dev 24:1253-65. 2010
    ..Taken together, our data demonstrate that DAXX functions as a bona fide histone chaperone involved in the replication-independent deposition of H3.3...
  7. ncbi 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...
  8. pmc Artemis C-terminal region facilitates V(D)J recombination through its interactions with DNA Ligase IV and DNA-PKcs
    Shruti Malu
    Immunology Institute, Mount Sinai School of Medicine, New York, NY 10029, USA
    J Exp Med 209:955-63. 2012
    ..Signal joint formation remains unaffected. Our data reveal that the C-terminal region of Artemis influences V(D)J recombination through its interaction with both Ligase IV and DNA-PKcs...
  9. pmc Mismatch-repair protein MSH6 is associated with Ku70 and regulates DNA double-strand break repair
    Ankita Shahi
    DNA Repair Research Center, Department of Pharmacology, Chosun University School of Medicine, 375 Seosuk dong, Gwangju, 501 759, South Korea
    Nucleic Acids Res 39:2130-43. 2011
    ..These results suggest a potential role for MSH6 in DSB repair through upregulation of NHEJ by association with Ku70...
  10. ncbi Conserved modes of recruitment of ATM, ATR and DNA-PKcs to sites of DNA damage
    Jacob Falck
    The Wellcome Trust and Cancer Research UK Gurdon Institute, and Department of Zoology, Cambridge University, Tennis Court Road, Cambridge CB2 1QN, UK
    Nature 434:605-11. 2005
    ....
  11. ncbi Artemis phosphorylated by DNA-dependent protein kinase associates preferentially with discrete regions of chromatin
    Sebastien Soubeyrand
    The Ottawa Health Research Institute, University of Ottawa, 725 Parkdale Avenue, Ottawa, Ont, Canada K1Y 4E9
    J Mol Biol 358:1200-11. 2006
    ..These foci were maintained upon DNA damage but failed to overlap with the damage-induced gammaH2AX. These results provide the expectation of a specific role for DNA-PK-phosphorylated Artemis in both naïve and damaged cells...
  12. ncbi Interaction between DNA-dependent protein kinase and a novel protein, KIP
    X Wu
    Department of Pathology, Washington University School of Medicine, St Louis, MO 63110, USA
    Mutat Res 385:13-20. 1997
    ..We discuss the interaction of DNA-PKcs with this novel calcium-binding protein family member in the context of possible kinase-phosphatase regulation of DNA end joining...
  13. ncbi Role of DNA-PK in the cellular response to DNA double-strand breaks
    Sandeep Burma
    Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA
    DNA Repair (Amst) 3:909-18. 2004
    ..The many roles of DNA-PK in the mammalian cell are discussed in this review with particular emphasis on recent advances in our understanding of the phosphorylation events that take place during the activation of DNA-PK at DNA breaks...
  14. pmc Phosphorylation of p50 NF-kappaB at a single serine residue by DNA-dependent protein kinase is critical for VCAM-1 expression upon TNF treatment
    Jihang Ju
    Department of Pharmacology and Experimental Therapeutics, Louisiana State University Health Sciences Center, New Orleans, Louisiana 70112, USA
    J Biol Chem 285:41152-60. 2010
    ..Together, these results elucidate a novel mechanism for the involvement of DNA-PK in the positive regulation of p50 NF-κB to drive VCAM-1 expression...
  15. doi Impact of PARP-1 and DNA-PK expression on survival in patients with glioblastoma multiforme
    Marju Kase
    Department of Radiotherapy, North Estonia Medical Centre, Tallinn, Estonia
    Radiother Oncol 101:127-31. 2011
    ..To analyze, whether higher tumor levels of DNA repair enzymes contribute to worse treatment results of glioblastoma multiforme (GBM) patients after postoperative radiotherapy...
  16. ncbi Identification of a PKB/Akt hydrophobic motif Ser-473 kinase as DNA-dependent protein kinase
    Jianhua Feng
    Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, Basel CH 4058, Switzerland
    J Biol Chem 279:41189-96. 2004
    ..We conclude that DNA-PK is a long sought after kinase responsible for the Ser-473 phosphorylation step in the activation of PKB...
  17. ncbi DNA-PK phosphorylation sites on Oct-1 promote cell survival following DNA damage
    C Schild-Poulter
    Department of Medicine, The Ottawa Health Research Institute, University of Ottawa, Ottawa, Ontario, Canada
    Oncogene 26:3980-8. 2007
    ..These results implicate Oct-1 as a primary effector in a DNA-PK-dependent cell survival pathway that is activated by double-stranded DNA breaks...
  18. pmc Trp-tRNA synthetase bridges DNA-PKcs to PARP-1 to link IFN-γ and p53 signaling
    Mathew Sajish
    The Skaggs Institute for Chemical Biology, Department of Molecular Biology, The Scripps Research Institute, La Jolla, California, USA
    Nat Chem Biol 8:547-54. 2012
    ..These and further results suggest an unexpected evolutionary expansion of the protein synthesis apparatus to a nuclear role that links major signaling pathways...
  19. ncbi Suppression of the poly(ADP-ribose) polymerase activity by DNA-dependent protein kinase in vitro
    Y Ariumi
    Institute for Virus Research, Kyoto University, Sakyo ku, Kyoto 606 8507, Japan
    Oncogene 18:4616-25. 1999
    ..Thus, DNA-PK suppresses PARP activity, probably through direct binding and/or sequestration of DNA-ends which serve as an important stimulator for both enzymes...
  20. ncbi Regulation of DNA-dependent protein kinase by the Lyn tyrosine kinase
    S Kumar
    Department of Adult Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA
    J Biol Chem 273:25654-8. 1998
    ..These results support the hypothesis that there are functional interactions between Lyn and DNA-PKcs in the response to DNA damage...
  21. ncbi Binding of Ku and c-Abl at the kinase homology region of DNA-dependent protein kinase catalytic subunit
    S Jin
    Division of Tumor Immunology, Dana Farber Cancer Institute, Boston, Massachusetts 02115, USA
    J Biol Chem 272:24763-6. 1997
    ..c-Abl phosphorylation of DNA-PKcs disassociates the DNA-PKcs.Ku complex. Thus, Ku and c-Abl provide opposing functions with regard to DNA-PK activity...
  22. ncbi Involvement of DNA-dependent protein kinase in regulation of stress-induced JNK activation
    S J Park
    Department of Biochemistry and Molecular Biology, Indiana University Cancer Center, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA
    DNA Cell Biol 20:637-45. 2001
    ..Together, our results suggest that DNA damage induces physical interaction between DNA-PK and JNK, which may in turn negatively affect JNK activity through JNK phosphorylation by DNA-PK...
  23. ncbi Model of full-length HIV-1 integrase complexed with viral DNA as template for anti-HIV drug design
    Rajeshri G Karki
    Laboratory of Medicinal Chemistry, Center for Cancer Research, National Cancer Institute, National Institutes of Health, DHHS, Frederick, MD 21702, USA
    J Comput Aided Mol Des 18:739-60. 2004
    ..The results indicate that the diketo-acid IN inhibitors probably chelate the metal ion in the catalytic site and also prevent the exposure of the 3'-processed end of the viral DNA to human DNA...
  24. pmc Autophosphorylation of DNA-dependent protein kinase regulates DNA end processing and may also alter double-strand break repair pathway choice
    Xiaoping Cui
    College of Veterinary Medicine and Department of Pathobiology and Diagnostic Investigation, Michigan State University, East Lansing, 48824, USA
    Mol Cell Biol 25:10842-52. 2005
    ..We conclude that separate DNA-PK autophosphorylation events may function reciprocally by not only regulating DNA end processing but also affecting DSB repair pathway choice...
  25. pmc Concordant and opposite roles of DNA-PK and the "facilitator of chromatin transcription" (FACT) in DNA repair, apoptosis and necrosis after cisplatin
    Janna Sand-Dejmek
    Department of Cancer Biology, Dana Farber Cancer Institute, 450 Brookline Avenue, Boston, Massachusetts 02215, USA
    Mol Cancer 10:74. 2011
    ..Inhibition of DNA-PK sensitizes cancer cells to cisplatin killing. The goal of this study is to elucidate the mechanism underlying the effects of DNA-PK on cisplatin sensitivity...
  26. doi Identification of DNA-dependent protein kinase catalytic subunit as a novel interaction partner of lymphocyte enhancer factor 1
    Atsushi Shimomura
    Department of Anatomy I, Fujita Health University School of Medicine, 1 98 Dengakugakubo, Kutsukake cho, Toyoake, Aichi, Japan
    Med Mol Morphol 46:14-9. 2013
    ..Identification of the interaction between LEF1 and DNA-PKcs may provide clues for a novel therapy for cancer treatment as well as for understanding LEF1-mediated transcriptional regulation...
  27. pmc An analysis of CAF-1-interacting proteins reveals dynamic and direct interactions with the KU complex and 14-3-3 proteins
    Maarten Hoek
    Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA
    J Biol Chem 286:10876-87. 2011
    ..These results highlight that CAF-1 has prominent interactions with the DNA repair machinery but that the N terminus is dispensable for the role of CAF-1 in DNA replication- and repair-coupled chromatin assembly...
  28. pmc DNA-Dependent protein kinase is not required for efficient lentivirus integration
    V Baekelandt
    Laboratory for Experimental Neurosurgery and Neuroanatomy, Katholieke Universiteit Leuven, Leuven, Belgium
    J Virol 74:11278-85. 2000
    ..However, no inhibition of lentivirus vector-mediated transduction or HIV-1 replication by 3-methoxybenzamide, a known PARP inhibitor, was observed. In conclusion, DNA-PK and PARP are not essential for lentivirus integration...
  29. pmc Modulation of Sp1 phosphorylation by human immunodeficiency virus type 1 Tat
    R F Chun
    Molecular Virology Section, Laboratory of Molecular Microbiology, National Institutes of Allergy and Infectious Diseases, Bethesda, Maryland 20892 0460, USA
    J Virol 72:2615-29. 1998
    ..Taken together, these findings suggest that activity at the HIV-1 promoter is influenced by phosphorylation of Sp1 which is affected by Tat and DNA-PK...
  30. pmc Gene for the catalytic subunit of the human DNA-activated protein kinase maps to the site of the XRCC7 gene on chromosome 8
    J D Sipley
    Biology Department, Brookhaven National Laboratory, Upton, NY 11973, USA
    Proc Natl Acad Sci U S A 92:7515-9. 1995
    ..This location is coincident with that of XRCC7, the gene that complements the DNA double-strand break repair and V(D)J recombination defects (where V is variable,..
  31. pmc Poly(ADP-ribose) Polymerase 1 Interacts with Nuclear Respiratory Factor 1 (NRF-1) and Plays a Role in NRF-1 Transcriptional Regulation
    Mohammad B Hossain
    Department of Biochemistry and Molecular Biology, Genes and Development Program of the Graduate School of Biomedical Sciences, The University of Texas M D Anderson Cancer Center, Houston, Texas 77030, USA
    J Biol Chem 284:8621-32. 2009
    ..Transient transfection and chromatin immunoprecipitation experiments suggest that PARP-1 plays a role during transcriptional activation by NRF-1. Our finding identifies a new aspect of transcriptional regulation used by NRF-1...
  32. pmc DNA-PK-dependent RPA2 hyperphosphorylation facilitates DNA repair and suppresses sister chromatid exchange
    Hungjiun Liaw
    Genome Instability Section, Genetics and Molecular Biology Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, United States of America
    PLoS ONE 6:e21424. 2011
    ..This pathway thus permits cells to repair DNA damage properly and increase cell viability...
  33. pmc DNA-PKCS binding to p53 on the p21WAF1/CIP1 promoter blocks transcription resulting in cell death
    Richard Hill
    Department of Microbiology and Immunology, Dalhousie University, Halifax, Nova Scotia, Canada
    Oncotarget 2:1094-108. 2011
    ..These data demonstrate that DNA-PKCS negatively regulates p21 expression by directly interacting with the p21 transcription machinery via p53, driving the cell towards apoptosis...
  34. ncbi The human double-stranded DNA-activated protein kinase phosphorylates the 90-kDa heat-shock protein, hsp90 alpha at two NH2-terminal threonine residues
    S P Lees-Miller
    Biology Department, Brookhaven National Laboratory, Upton, New York 11973
    J Biol Chem 264:17275-80. 1989
    ..Mouse hsp86 and rabbit hsp90 alpha are homologous to human hsp90 alpha; both heterologous proteins are phosphorylated at the same amino-terminal threonines by the human dsDNA-activated protein kinase...
  35. pmc Inhibition of homologous recombination by variants of the catalytic subunit of the DNA-dependent protein kinase (DNA-PKcs)
    Erin Convery
    Department of Pathobiology and Diagnostic Investigation, Michigan State University, East Lansing, MI 48824, USA
    Proc Natl Acad Sci U S A 102:1345-50. 2005
    ....
  36. ncbi Three-dimensional structure and regulation of the DNA-dependent protein kinase catalytic subunit (DNA-PKcs)
    Angel Rivera-Calzada
    Centro de Investigaciones Biologicas, Consejo Superior de Investigaciones Cientificas CSIC, Ramiro de Maeztu 9, Campus Universidad Complutense, 28040 Madrid, Spain
    Structure 13:243-55. 2005
    ..Comparison of DNA-PKcs with another PIKK DNA repair factor, ATM, defines a common architecture for this important protein family...
  37. ncbi HIV-1 integration: an interplay between HIV-1 integrase, cellular and viral proteins
    Bénédicte Van Maele
    Laboratory for Molecular Virology and Gene Therapy, KULAK and KULeuven, Flanders, Belgium
    AIDS Rev 7:26-43. 2005
    ..In this review we summarize the candidate cellular proteins involved in the HIV-1 integration process identified so far and discuss their potential roles during HIV-1 replication...
  38. ncbi Protein kinase Cepsilon activates protein kinase B/Akt via DNA-PK to protect against tumor necrosis factor-alpha-induced cell death
    Dongmei Lu
    Department of Molecular Biology and Immunology, University of North Texas Health Science Center, Fort Worth, Texas 76107, USA
    J Biol Chem 281:22799-807. 2006
    ..These results suggest that PKCepsilon activates Akt via DNA-PK to mediate its antiapoptotic function. Furthermore, we report for the first time that DNA-PK can regulate receptor-initiated apoptosis via Akt...
  39. doi Genetic variants of the XRCC7 gene involved in DNA repair and risk of human bladder cancer
    Shou Yu Wang
    Institute of Toxicology, School of Public Health, Nanjing Medical University, Nanjing, China
    Int J Urol 15:534-9. 2008
    To investigate the association between the polymorphisms of the KU70 and X-ray repair cross complementing group 7 (XRCC7) genes and the risk of bladder cancer.
  40. doi Regulation of DNA-dependent protein kinase by protein kinase CK2 in human glioblastoma cells
    B B Olsen
    Department of Biochemistry and Molecular Biology, University of Southern Denmark, Odense, Denmark
    Oncogene 29:6016-26. 2010
    ..These results indicate that CK2 has an important role in the modulation of DNA-PKcs activity and its phosphorylation status providing important insights into the mechanisms by which DNA-PKcs is regulated in vivo...
  41. ncbi The DNA-dependent protein kinase: requirement for DNA ends and association with Ku antigen
    T M Gottlieb
    Wellcome CRC Institute, Cambridge, England
    Cell 72:131-42. 1993
    ..The implications of the unusual DNA binding mode and multicomponent nature of the DNA-PK are discussed...
  42. ncbi Sequence-specific DNA binding and transcription factor phosphorylation by Ku Autoantigen/DNA-dependent protein kinase. Phosphorylation of Ser-527 of the rat glucocorticoid receptor
    W Giffin
    Department of Medicine, University of Ottawa, Loeb Medical Research Institute, Ottawa Civic Hospital, Ottawa, Ontario, Canada K1Y 4E9
    J Biol Chem 272:5647-58. 1997
    ..This site occurs adjacent the GR nuclear localization sequence between the DNA and ligand binding domains of GR, and thus its phosphorylation, if confirmed, has the potential to affect receptor function in vivo...
  43. ncbi Inhibition of phosphoinositide 3-kinase related kinases by the radiosensitizing agent wortmannin
    J N Sarkaria
    Division of Oncology Research, Mayo Clinic, Rochester, Minnesota 55905, USA
    Cancer Res 58:4375-82. 1998
    ..These results identify wortmannin as an inhibitor of ATM activity and suggest that ATM and DNA-PK are relevant targets for the radiosensitizing effect of this drug in cancer cells...
  44. ncbi Recruitment of ATM protein to double strand DNA irradiated with ionizing radiation
    K Suzuki
    Laboratory of Radiation and Life Science, School of Pharmaceutical Sciences, Nagasaki University, 1 14 Bunkyo machi, Nagasaki 852 8521, Japan
    J Biol Chem 274:25571-5. 1999
    ..These results indicate that the ATM protein is recruited to the site of DNA damage and it recognizes double strand breaks by itself or through an association with other DNA-binding protein other than DNA-PK and Ku80 proteins...
  45. ncbi Purification and characterization of ATM from human placenta. A manganese-dependent, wortmannin-sensitive serine/threonine protein kinase
    D W Chan
    Department of Biological Sciences, University of Calgary, Calgary, Alberta T2N 1N4, Canada
    J Biol Chem 275:7803-10. 2000
    ..The related protein, DNA-dependent protein kinase catalytic subunit, also phosphorylated PHAS-I, RPA, and Chk2 in the presence of manganese, suggesting that the requirement for manganese is a characteristic of this class of enzyme...
  46. pmc The RNA binding protein nuclear factor 90 functions as both a positive and negative regulator of gene expression in mammalian cells
    Trevor W Reichman
    Department of Biochemistry and Molecular Biology, New Jersey Medical School and Graduate School of Biomedical Sciences, University of Medicine and Dentistry of New Jersey, Newark, New Jersey 07013 2714, USA
    Mol Cell Biol 22:343-56. 2002
    ..This report characterizes NF90 as both a positive and negative regulator of gene expression, depending on the promoter context, and suggests a role for NF45 as a regulator of NF90...
  47. ncbi Kinetic properties of p53 phosphorylation by the human vaccinia-related kinase 1
    Ramiro Barcia
    Instituto de Biologia Molecular y Celular del Cancer, Universidad de Salamanca, Campus Miguel de Unamuno, Salamanca, E 37007, Spain
    Arch Biochem Biophys 399:1-5. 2002
    ..The kinase phosphorylates p53 with a K(m) of 1 microM and is well suited to respond to the variations of intracellular p53 concentration, which fluctuates as a response to different types of cellular stress...
  48. ncbi Hairpin opening and overhang processing by an Artemis/DNA-dependent protein kinase complex in nonhomologous end joining and V(D)J recombination
    Yunmei Ma
    Norris Comprehensive Cancer Center, Rm 5428, Departments of Biochemistry and Molecular Biology, Pathology, Biological Sciences, and Molecular Microbiology and Immunology, 1441 Eastlake Avenue, Los Angeles, CA 90033, USA
    Cell 108:781-94. 2002
    ....
  49. ncbi Coordinated assembly of Ku and p460 subunits of the DNA-dependent protein kinase on DNA ends is necessary for XRCC4-ligase IV recruitment
    Patrick Calsou
    Institut de Pharmacologie et de Biologie Structurale, CNRS UMR 5089, 205 route de Narbonne, 31077, Cedex 4, Toulouse, France
    J Mol Biol 326:93-103. 2003
    ..DNA-PK comprises Ku70/Ku80 heterodimer and the kinase subunit DNA-PKcs (p460)...
  50. pmc Functional and biochemical dissection of the structure-specific nuclease ARTEMIS
    Ulrich Pannicke
    Institute for Clinical Transfusion Medicine and Immunogenetics, and Department of Transfusion Medicine, University of Ulm, Ulm, Germany
    EMBO J 23:1987-97. 2004
    ..These results indicate that the hairpin-opening activity of ARTEMIS and/or its overhang endonucleolytic activity are necessary but its exonuclease activity is not sufficient for the process of V(D)J recombination...
  51. pmc XRCC1 is phosphorylated by DNA-dependent protein kinase in response to DNA damage
    Nicolas Levy
    Département Intégrité du Génome de l UMR 7175, CNRS, Ecole Superieure de Biotechnologie de Strasbourg, Boulevard S Brant, BP 10413, F 67412 Illkirch cedex, France
    Nucleic Acids Res 34:32-41. 2006
    ..The functional association between XRCC1 and DNA-PK in response to IR provides the first evidence for their involvement in a common DSB repair pathway...
  52. pmc Radiation-induced caveolin-1 associated EGFR internalization is linked with nuclear EGFR transport and activation of DNA-PK
    Klaus Dittmann
    Division of Radiobiology and Environmental Research, Department of Radiation Oncology University of Tübingen, Röntgenweg 11, 72076 Tubingen, Germany
    Mol Cancer 7:69. 2008
    ..To elucidate the role of src kinase in caveolin-1 driven internalization and nuclear transport of EGFR linked to regulation of DNA-repair in irradiated cells...
  53. pmc Transcriptional activation of DNA-dependent protein kinase catalytic subunit gene expression by oestrogen receptor-alpha
    Senad Medunjanin
    Division of Cardiology, Department of Internal Medicine, Dresden University of Technology, Dresden, Germany
    EMBO Rep 11:208-13. 2010
    ..This previously unknown mechanism of DNA-PK regulation sheds new light on tumour biology and reveals new possibilities for the prevention and therapy of E2-sensitive proliferative diseases...
  54. pmc Radiosensitivity profiles from a panel of ovarian cancer cell lines exhibiting genetic alterations in p53 and disparate DNA-dependent protein kinase activities
    Gregory T Langland
    Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA
    Oncol Rep 23:1021-6. 2010
    ..These data suggest that the activity of regulatory molecules such as p53 may be better indicators of radiation sensitivity than DNA repair enzymes such as DNA-PK in ovarian cancer...
  55. pmc Regulatory roles of tankyrase 1 at telomeres and in DNA repair: suppression of T-SCE and stabilization of DNA-PKcs
    Ryan C Dregalla
    Department of Environmental and Radiological Health Sciences, Colorado State University, Fort Collins, 80523 1618, USA
    Aging (Albany NY) 2:691-708. 2010
    ..We provide the first evidence for regulation of DNA-PKcs by tankyrase 1 PARP activity and taken together, identify roles of tankyrase 1 with implications not only for DNA repair and telomere biology, but also for cancer and aging...
  56. ncbi Low expression of Ku70/80, but high expression of DNA-PKcs, predict good response to radiotherapy in early breast cancer
    Karin Söderlund Leifler
    Department of Clinical and Experimental Medicine, Division of Surgery and Clinical Oncology, Linkoping University, Linkoping, Sweden
    Int J Oncol 37:1547-54. 2010
    ..We believe that the results reflect the different roles of DNA-PKcs and Ku70/80 in repair and cell death regulation after DNA damage. These differences could be of importance when developing drugs that target DNA repair...
  57. pmc Inactivation of DNA-dependent protein kinase by protein kinase Cdelta: implications for apoptosis
    A Bharti
    Cancer Pharmacology, Dana Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA
    Mol Cell Biol 18:6719-28. 1998
    ..These findings support the hypothesis that functional interactions between PKCdelta and DNA-PK contribute to DNA damage-induced apoptosis...
  58. pmc DNA-dependent protein kinase suppresses double-strand break-induced and spontaneous homologous recombination
    Chris Allen
    Department of Molecular Genetics and Microbiology, University of New Mexico School of Medicine, Albuquerque, NM 87131, USA
    Proc Natl Acad Sci U S A 99:3758-63. 2002
    ....
  59. ncbi [Expression of GLUT-1, p63 and DNA-Pkcs in serous ovarian tumors and their significance]
    Shu Li Shao
    Department of Gynecology, Tumor Hospital of Shanxi Province, Taiyuan 030013, China
    Zhonghua Zhong Liu Za Zhi 29:697-700. 2007
    ..To investigate the expression of GLUT1, p63 and DNA-Pkcs in serous ovarian tumors and their significance...
  60. ncbi Mapping of amino acid residues in the p34 subunit of human single-stranded DNA-binding protein phosphorylated by DNA-dependent protein kinase and Cdc2 kinase in vitro
    H Niu
    Graduate Program in Molecular Biology, Memorial Sloan Kettering Cancer Center and Cornell University Graduate School of Medical Sciences, New York, New York 10021, USA
    J Biol Chem 272:12634-41. 1997
    ..We also identified Ser-29 as the major Cdc2 kinase phosphorylation site in the p34 subunit...
  61. pmc The C terminus of Ku80 activates the DNA-dependent protein kinase catalytic subunit
    B K Singleton
    MRC Cell Mutation Unit, University of Sussex, Brighton BN1 9RR, United Kingdom
    Mol Cell Biol 19:3267-77. 1999
    ..This residue is conserved among species and lies outside of the previously reported Ku70-Ku80 interaction domain. The mutational change nonetheless abrogates the Ku70-Ku80 interaction and DNA end-binding activity...
  62. pmc Interferon regulatory factor-3 is an in vivo target of DNA-PK
    Alla Y Karpova
    Department of Pathology, Harvard Medical School, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 99:2818-23. 2002
    ..As such this study contributes to a more integrated view of the cellular responses to various cellular stress signals...
  63. ncbi Conversion of phosphoglycolate to phosphate termini on 3' overhangs of DNA double strand breaks by the human tyrosyl-DNA phosphodiesterase hTdp1
    Kedar V Inamdar
    Department of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond, VA 23298, USA
    J Biol Chem 277:27162-8. 2002
    ..The results suggest a role for hTdp1 in repair of free radical-mediated DNA double strand breaks bearing terminally blocked 3' overhangs...
  64. ncbi The DNA-dependent protein kinase interacts with DNA to form a protein-DNA complex that is disrupted by phosphorylation
    Dennis Merkle
    Department of Biochemistry and Molecular Biology, University of Calgary, 3300 Hospital Drive, Calgary AB, T2N 4N1, Canada
    Biochemistry 41:12706-14. 2002
    ..We propose that autophosphorylation of DNA-PK plays an important regulatory role in DNA double-strand break repair by regulating the assembly and disassembly of the DNA-PK-DNA complex...
  65. ncbi Down-regulation of histone H2B by DNA-dependent protein kinase in response to DNA damage through modulation of octamer transcription factor 1
    Caroline Schild-Poulter
    Department of Medicine, University of Ottawa, The Ottawa Health Research Institute, 725 Parkdale Avenue, Ottawa, Ontario K1Y 4E9, Canada
    Cancer Res 63:7197-205. 2003
    ..These results suggest a mechanism for the regulation of Oct-1 in response to DNA damage through specific phosphorylation within the NH(2)-terminal transcriptional regulatory domain...
  66. pmc DNA-PK is activated by nucleosomes and phosphorylates H2AX within the nucleosomes in an acetylation-dependent manner
    Eun Jung Park
    Division of Molecular Life Sciences and Center for Cell Signalling Research, Ewha Womans University, Seoul 120 750, Korea
    Nucleic Acids Res 31:6819-27. 2003
    ....
  67. pmc DNA-dependent PK inhibits adeno-associated virus DNA integration
    Sihong Song
    Department of Pharmaceutics, Powell Gene Therapy Center, Genetics Institute, University of Florida, Gainesville, FL 32610, USA
    Proc Natl Acad Sci U S A 101:2112-6. 2004
    ..In summary, we have provided evidence that DNA-PK inhibits AAV integration both in vitro and in vivo...
  68. ncbi Expression of DNA-dependent protein kinase in human granulocytes
    Annahita Sallmyr
    Department of Medical Microbiology, Lund University, Malmo University Hospital, S 205 02 Malmo, Sweden
    Cell Res 14:331-40. 2004
    ..In conclusion, our findings provide evidence of reduced, not depleted expression of DNA-PK during the mature stages of myeloid differentiation...
  69. ncbi Complex H2AX phosphorylation patterns by multiple kinases including ATM and DNA-PK in human cells exposed to ionizing radiation and treated with kinase inhibitors
    Hongyan Wang
    Department of Radiation Oncology, Division of Experimental Radiation Oncology, Kimmel Cancer Center, Jefferson Medical College, Philadelphia, Pennsylvania, USA
    J Cell Physiol 202:492-502. 2005
    ..The results in aggregate implicate DNA-PK, ATM and possibly other kinases in H2AX phosphorylation. The functional significance and the mechanisms of coordination in space and time of these multiple inputs require further investigation...
  70. ncbi Regulation of CHK2 by DNA-dependent protein kinase
    Jia Li
    Department of Pathology, Yale University School of Medicine, New Haven, Connecticut 06510, USA
    J Biol Chem 280:12041-50. 2005
    ..Ionizing radiation-induced Chk2 phosphorylation was wortmannin-sensitive in ATM-defective cells with depleted ATR. These results suggest that DNA-PK augments ATM and ATR in activation of Chk2 by DNA damage...
  71. ncbi The Artemis:DNA-PKcs endonuclease cleaves DNA loops, flaps, and gaps
    Yunmei Ma
    Department of Pathology, Norris Comprehensive Cancer Center, Rm 5428, University of Southern California Keck School of Medicine, Los Angeles, CA 90089 9176, USA
    DNA Repair (Amst) 4:845-51. 2005
    ..Additionally, the flexibility of the Artemis:DNA-PKcs nuclease may be important in removing secondary structures that hinder processing of DNA ends during NHEJ...
  72. doi FACT-mediated exchange of histone variant H2AX regulated by phosphorylation of H2AX and ADP-ribosylation of Spt16
    Kyu Heo
    Department of Biochemistry and Molecular Biology, Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA 90089, USA
    Mol Cell 30:86-97. 2008
    ..Thus, these data establish FACT as the major regulator involved in H2AX exchange process that is modulated by H2AX phosphorylation and Spt16 ADP-ribosylation...
  73. ncbi DNA-activated protein kinase in Raji Burkitt's lymphoma cells. Phosphorylation of c-Myc oncoprotein
    S Iijima
    Department of Pathological Biochemistry, Tokyo Medical and Dental University, Japan
    Eur J Biochem 206:595-603. 1992
    ..Phosphopeptide mapping and phosphoamino acid analysis indicated that DNA-PK phosphorylates c-Myc in vitro at several serine residues...
  74. pmc A DNA-activated protein kinase from HeLa cell nuclei
    T Carter
    Department of Biological Sciences, St John s University, Jamaica, New York 11439
    Mol Cell Biol 10:6460-71. 1990
    ..These characteristics identify DNA-PK as distinct from other protein kinases described in the literature and suggest that activation by DNA is an important feature of the enzyme's in vivo function...
  75. ncbi DNA-dependent protein kinase catalytic subunit: a relative of phosphatidylinositol 3-kinase and the ataxia telangiectasia gene product
    K O Hartley
    Wellcome Trust Cancer Research Campaign Institute, Cambridge University, England
    Cell 82:849-56. 1995
    ..The relationship of these proteins to DNA-PKcs provides important clues to their mechanisms of action...
  76. pmc Interleukin-1 beta-converting enzyme-like protease cleaves DNA-dependent protein kinase in cytotoxic T cell killing
    Q Song
    Queensland Cancer Fund Research Unit, Queensland Institute of Medical Research, Bancroft Centre, PO Royal Brisbane Hospital, Herston, Australia
    J Exp Med 184:619-26. 1996
    ..This study demonstrates for the first time that the cleavage of DNA-PKcs in this intact cell system is exclusively due to an ICE-like protease...
  77. ncbi Sites of UV-induced phosphorylation of the p34 subunit of replication protein A from HeLa cells
    M Zernik-Kobak
    Department of Environmental Health, University of Cincinnati School of Medicine, Cincinnati, Ohio 45267 0056, USA
    J Biol Chem 272:23896-904. 1997
    ..The capacity of purified DNA-PK to phosphorylate many of these same sites on RPA-p34 in vitro implicates DNA-PK or a kinase with similar specificity in the UV-induced hyperphosphorylation of RPA in vivo...
  78. ncbi Heat shock transcription factor 1 binds selectively in vitro to Ku protein and the catalytic subunit of the DNA-dependent protein kinase
    J Huang
    Gene Regulation Program, Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, Georgia 30912, USA
    J Biol Chem 272:26009-16. 1997
    ..The ability of HSF1 to interact with both components of DNA-PK provides a potential mechanism for the activation of DNA-PK in response to heat and other forms of stress...
  79. pmc DNA-dependent protein kinase: DNA binding and activation in the absence of Ku
    O Hammarsten
    Department of Medicine, Stanford University Medical Center, CA 94305 5115, USA
    Proc Natl Acad Sci U S A 95:525-30. 1998
    ..DNA-PK consists of a 460-kDa subunit (p460) that contains a putative kinase domain and a heterodimeric subunit (Ku) that binds to double-stranded DNA ends...
  80. ncbi DNA-dependent protein kinase interacts with antigen receptor response element binding proteins NF90 and NF45
    N S Ting
    Department of Biological Sciences, University of Calgary, Alberta, Canada
    J Biol Chem 273:2136-45. 1998
    ..Together, our data suggest that NF90, in complex with NF45, interacts with DNA-PKcs and Ku on DNA and that NF90 and NF45 may be important for the function of DNA-PK...
  81. ncbi The complexity of p53 modulation: emerging patterns from divergent signals
    A J Giaccia
    Mayer Cancer Biology Research Laboratory, Department of Radiation Oncology, Stanford University, Stanford, California 94305 5468, USA
    Genes Dev 12:2973-83. 1998
  82. pmc Replication-mediated DNA damage by camptothecin induces phosphorylation of RPA by DNA-dependent protein kinase and dissociates RPA:DNA-PK complexes
    R G Shao
    Laboratory of Molecular Pharmacology, Division of Basic Sciences, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 4255, USA
    EMBO J 18:1397-406. 1999
    ....
  83. ncbi A role for DNA-PK in retroviral DNA integration
    R Daniel
    Institute for Cancer Research, Fox Chase Cancer Center, 7701 Burholme Avenue, Philadelphia, PA 19111, USA
    Science 284:644-7. 1999
    ..These results suggest that the initial events in retroviral integration are detected as DNA damage by the host cell and that completion of the integration process requires the DNA-PK-mediated repair pathway...
  84. pmc Mapping of protein-protein interactions within the DNA-dependent protein kinase complex
    D Gell
    Wellcome CRC Institute, Tennis Court Road, Cambridge CB2 1QR, UK
    Nucleic Acids Res 27:3494-502. 1999
    ..These data suggest that Ku has evolved to become part of the DNA-PK holo-enzyme by acquisition of a protein-protein interaction motif at the C-terminus of Ku80...
  85. pmc Wortmannin potentiates integrase-mediated killing of lymphocytes and reduces the efficiency of stable transduction by retroviruses
    R Daniel
    Fox Chase Cancer Center, Institute for Cancer Research, Philadelphia, Pennsylvania 19111, USA
    Mol Cell Biol 21:1164-72. 2001
    ..The studies also suggest that cells can be sensitized to such killing and stable retroviral DNA integration blocked by drugs that inhibit cellular DNA repair pathways...
  86. pmc Role of the non-homologous DNA end joining pathway in the early steps of retroviral infection
    L Li
    Infectious Disease Laboratory, The Salk Institute, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA
    EMBO J 20:3272-81. 2001
    ..We propose that the double-strand ends present in unintegrated cDNA promote apoptosis, as is known to be the case for chromosomal double-strand breaks, and cDNA circularization removes the pro-apoptotic signal...
  87. ncbi Replication protein A2 phosphorylation after DNA damage by the coordinated action of ataxia telangiectasia-mutated and DNA-dependent protein kinase
    H Wang
    Department of Radiation Oncology, Kimmel Cancer Center, Jefferson Medical College, Philadelphia, Pennsylvania 19107, USA
    Cancer Res 61:8554-63. 2001
    ....
  88. ncbi Werner protein is a target of DNA-dependent protein kinase in vivo and in vitro, and its catalytic activities are regulated by phosphorylation
    Parimal Karmakar
    Laboratory of Molecular Gerontology, NIA, National Institutes of Health, Baltimore, Maryland 21224, USA
    J Biol Chem 277:18291-302. 2002
    ..Thus, WRN protein is a target for DNA-PK phosphorylation in vitro and in vivo, and this phosphorylation may be a way of regulating its different catalytic activities, possibly in the repair of DNA dsb...
  89. pmc Synapsis of DNA ends by DNA-dependent protein kinase
    Lisa G DeFazio
    Departments of Medicine and Biochemistry, Stanford University, Stanford, CA 94305, USA
    EMBO J 21:3192-200. 2002
    ..Our results suggest that DNA-PK(CS) brings DNA ends together and then undergoes activation of its kinase, presumably to regulate subsequent steps for processing and ligation of the ends...
  90. pmc Identification of in vitro and in vivo phosphorylation sites in the catalytic subunit of the DNA-dependent protein kinase
    Pauline Douglas
    Department of Biochemistry and Molecular Biology, University of Calgary, 3330 Hospital Drive, Calgary, AB, T2N 4N1, Canada
    Biochem J 368:243-51. 2002
    ..Moreover, we show that DNA-PKcs is phosphorylated in vivo at Thr2609, Ser2612, Thr2638 and Thr2647 in okadaic acid-treated human cells. We propose that phosphorylation of these sites may play an important role in DNA-PK function...
  91. pmc Autophosphorylation of the DNA-dependent protein kinase catalytic subunit is required for rejoining of DNA double-strand breaks
    Doug W Chan
    Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, California 94720, USA
    Genes Dev 16:2333-8. 2002
    ..Mutation of Thr2609 to Ala leads to radiation sensitivity and impaired DSB rejoining. These findings establish that Ku-dependent phosphorylation of DNA-PKcs at Thr2609 is required for the repair of DSBs by NHEJ...
  92. ncbi Defining interactions between DNA-PK and ligase IV/XRCC4
    Hsin Ling Hsu
    Department of Cell and Molecular Biology, Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA
    DNA Repair (Amst) 1:225-35. 2002
    ..Our data defines the specific protein pairs involved in the association of DNA-PK and ligase IV/XRCC4, and suggests a molecular mechanism for coordinating the assembly of the DNA repair complex at DNA breaks...
  93. pmc Autophosphorylation of the catalytic subunit of the DNA-dependent protein kinase is required for efficient end processing during DNA double-strand break repair
    Qi Ding
    College of Veterinary Medicine and Department of Pathobiology and Diagnostic Investigation, Michigan State University, East Lansing, Michigan 48824, USA
    Mol Cell Biol 23:5836-48. 2003
    ..However, autophosphorylation at these sites may not be sufficient for kinase disassembly...
  94. ncbi Up-regulation of DNA-dependent protein kinase correlates with radiation resistance in oral squamous cell carcinoma
    Satoru Shintani
    Department of Oral and Maxillofacial Surgery, Ehime University School of Medicine, Shigenobu cho, Onsen gun, Ehime, 791 0295, Japan
    Cancer Sci 94:894-900. 2003
    ..DNA-PKcs might be a molecular target for a novel radiation sensitization therapy of OSCC...
  95. pmc DNA-PKcs function regulated specifically by protein phosphatase 5
    Thomas Wechsler
    Department of Microbiology and Immunology and UCSF Cancer Center, University of California, San Francisco, CA 94143, USA
    Proc Natl Acad Sci U S A 101:1247-52. 2004
    ..Cells with either hypo- or hyperphosphorylation of DNA-PKcs at these sites show increased radiation sensitivity...
  96. pmc The metallo-beta-lactamase/beta-CASP domain of Artemis constitutes the catalytic core for V(D)J recombination
    Catherine Poinsignon
    Développement Normal et Pathologique de Système Immunitaire, INSERM U429, Hopital Necker Enfants Malades, 75015 Paris, France
    J Exp Med 199:315-21. 2004
    ....
  97. ncbi Non-homologous end joining requires that the DNA-PK complex undergo an autophosphorylation-dependent rearrangement at DNA ends
    Yeturu V R Reddy
    Lineberger Comprehensive Cancer Center and Department of Biochemistry and Biophysics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA
    J Biol Chem 279:39408-13. 2004
    ..Autophosphorylation at ABCDE sites thus apparently directs a rearrangement of the DNA-PK complex that ensures access to broken ends and joining steps are coupled together within a synaptic complex, making repair more accurate...
  98. ncbi Effects of novel inhibitors of poly(ADP-ribose) polymerase-1 and the DNA-dependent protein kinase on enzyme activities and DNA repair
    Stephany J Veuger
    Northern Institute for Cancer Research, University of Newcastle, Newcastle upon Tyne, NE2 4HH, UK
    Oncogene 23:7322-9. 2004
    ..These data point to combined inhibition of PARP-1 and DNA-PK as a powerful strategy for tumor radiosensitization...
  99. ncbi Polymorphisms of DNA repair genes and risk of glioma
    Li E Wang
    Department of Epidemiology, The University of Texas M D Anderson Cancer Center, Houston, Texas 77030, USA
    Cancer Res 64:5560-3. 2004
    ..breaks, such as XRCC1 in single-strand break repair, XRCC3 and RAD51 in homologous recombination repair, and XRCC7 in nonhomologous end joining double-strand break repair...
  100. ncbi Potentiality of DNA-dependent protein kinase to phosphorylate Ser46 of human p53
    Shingo Komiyama
    Department of Radiation Oncology, Graduate School of Medicine, The University of Tokyo, 7 3 1 Hongo, Bunkyo ku, Tokyo 113 0033, Japan
    Biochem Biophys Res Commun 323:816-22. 2004
    ..These results collectively suggested two pathways for IR-induced phosphorylation of Ser46, i.e., direct phosphorylation by DNA-PK and indirect phosphorylation via ATM...
  101. ncbi DNA-dependent protein kinase and XRCC4-DNA ligase IV mobilization in the cell in response to DNA double strand breaks
    Jerome Drouet
    Institut de Pharmacologie et de Biologie Structurale, CNRS UMR 5089, 205 route de Narbonne, 31077 Toulouse, Cedex 4, France
    J Biol Chem 280:7060-9. 2005
    ..Altogether these results offer insights into the interplay between key NHEJ proteins during this repair process in the cell...

Research Grants69

  1. Lauren Endres; Fiscal Year: 2014
    ..PARP, XRCC1 and polynucleotide kinase;for DSBR, RAD family proteins, XRCC2 and 3, BRCA1 and 2, Ku70 and 86, and DNAPK)...
  2. Sandeep Burma; Fiscal Year: 2015
    ..This would help to identify vulnerable nodes that could be targeted for effective radiosensitization of these tumors. ..
  3. Jianming Qiu; Fiscal Year: 2016
    ..e., EPCs ex vivo-expanded under hypoxic conditions for B19V in this application. ..
  4. Thomas M Aune; Fiscal Year: 2014
    ..To test this hypothesis, we will determine the extent to which this molecular and cellular phenotype is present in HLA-DRB1*04 positive and negative subjects with and without rheumatoid arthritis. ..
  5. Scanning Correlation Microscopy Methods for Quantifying DNA Repair Kinetics
    Georgios Alexandrakis; Fiscal Year: 2012
    ..Therefore, the proposed methods are very generally applicable to the DNA repair field and beyond. ..
  6. CryoEM Structural Studies of DNA-PKcs and Nonhomologous End Joining Complexes
    Phoebe L Stewart; Fiscal Year: 2013
    ..Ultimately this information will be helpful in understanding and treating cancer, severe combined immune deficiency (SCID), and sensitivity to ionizing radiation (RS-SCID). ..
  7. JEREMY MICHAEL STARK; Fiscal Year: 2016
    ..Our proposed study is also innovative because it will provide insight into the importance of incorrect end use during EJ for radiation toxicity, which will lead to new therapeutic strategies for tumor radiosensitization. ..
  8. David J Chen; Fiscal Year: 2016
    ..Taken together, these underlie the importance of understanding the coordination and function of DSB repair and insights into repair mechanisms will ultimately translate into clinical targets and benefits. ..
  9. Jean Gautier; Fiscal Year: 2015
    ..Finally, in the fourth aim, we will validate and initiate the characterization of novel components of the DSB proteome identified in our studies. ..
  10. Benjamin Ping Chi Chen; Fiscal Year: 2016
    DESCRIPTION (provided by applicant): The DNA dependent protein kinase catalytic subunit (DNA-PKcs) and its DNA-binding partner the Ku70/80 heterodimer are the key components of the non-homologous end-joining (NHEJ) pathway...
  11. DNA PK IN RADIATION DAMAGE REPAIR AND LYMPHOMAGENESIS
    Gloria Li; Fiscal Year: 2002
    ..Furthermore, our studies should verify whether there is a role of Ku70 in lymphomagenesis, and specifically whether Ku70 may be considered as a candidate tumor suppressor gene. ..
  12. Michael R Lieber; Fiscal Year: 2015
    ..In the long-term, all of these studies will help establish optimal therapy for many human SCID patients and to understand the human immune repertoire. ..
  13. Mechansim of activation of innate immunity by ISS-DNA
    Wen Ming Chu; Fiscal Year: 2013
    ..To balance the benefits and side effects of CpG-DNA, we need to understand the molecular mechanisms by which DNAPK and HMGB1 activate the CpG- DNA pathway...
  14. Mechanisms underlying the generation of oncogenic chromosomal translocations
    CHERYL JACOBS SMITH; Fiscal Year: 2013
    ..Furthermore, the proposed studies will provide a more in-depth understanding of the mechanisms underlying the generation of oncogenic events that lead to tumorigenesis. ..
  15. DAVID MICHAEL LANGENAU; Fiscal Year: 2016
    ..Such broad reaching applications for immune compromised zebrafish spans the mission of many NIH institutes. ..
  16. ROLE OF DNA DEPENDENT PROTEIN KINASE IN DNA REPAIR
    Paul Labhart; Fiscal Year: 2002
    ....
  17. Molecular Genetic Study of Repair of Radiation Damage
    THOMAS STAMATO; Fiscal Year: 2003
    ..region (MAR) DNA sequences and that this interaction requires the DNA-end-binding protein Ku, DNA dependent protein kinase catalytic subunit (DNA-PKcs), and other unknown factors in nuclear extract...
  18. END JOINING REACTION IN DNA REPAIR & V(D)J RECOMBINATION
    Gilbert Chu; Fiscal Year: 2005
    ..Experiments will determine whether phosphatases play a role in NHEJ, and identify physiologically relevant targets of DNA-PKcs. ..
  19. Gamma-ray-induced mutagen sensitivity in breast cancer
    Li E Wang; Fiscal Year: 2005
    ..2): To determine the correlation between polymorphisms of three select DNA repair genes (XRCC3, XRCC7 and RAD51) involved in DSBR and the G2 chromosomal radiosensitivity (phenotype) and their modulation of risk ..
  20. DNA STRAND BREAKS AND THE GENETIC BASIS OF LYMPHOMAS
    Gilbert Chu; Fiscal Year: 2001
    ..DSB repair requires four genes: XRCC4, XRCC5 (Ku86), XRCC6 (Ku70), and XRCC7 (DNA-PKcs, the catalytic subunit of DNA-dependent protein kinase), the latter of which is mutated in the scid ..
  21. MECHANISMS OF FORMATION OF TERMINAL DELETIONS
    John Murnane; Fiscal Year: 2007
    ....
  22. TOPOISOMERASE DRUG ACTIONS AT NUCLEAR MATRIX DNA DOMAIN
    Daniel Fernandes; Fiscal Year: 2003
    ....
  23. Hematopoietic Stem Cell Transposon Therapy for Severe Combined Immunodeficiency
    Jakub Tolar; Fiscal Year: 2009
    ..The fundamental insights gained from these studies will have broad implications relevant to both gene therapy and treatment of blood diseases. ..
  24. KU, TELOMERE MAINTENANCE AND CELLULAR SENESCENCE
    David Chen; Fiscal Year: 2004
    ..These studies are critical for a further understanding of telomere maintenance, which will provide a better understanding of cellular senescence. ..
  25. MECHANISM OF CODING JOINT FORMATION
    Patricia Cortes; Fiscal Year: 2003
    ..As VDJ recombination and DNA double strand break repair are rapidly converging and it is clear that they share a number of factors, our studies will contribute to the understanding of both of these important process. ..
  26. MECHANISMS OF RADIATION INDUCED GENOMIC INSTABILITY
    ANDREW GROSOVSKY; Fiscal Year: 1999
    ..sub unit (DNA-PK) Cho cell mutant, V-3, will be isolated and restored to radio resistance by instruction of the XRCC7 gene which encode DNA-PK...
  27. ROLES OF DNA PK IN DNA DOUBLE STRAND BREAK REPAIR
    David Chen; Fiscal Year: 2001
    ..To do this they will express various mutant versions of the three proteins in cells with defined genetic backgrounds that lack the Ku70, the Ku80 or the DNA-PKcs functions. ..
  28. Mouse Model for Chemical and Radiation Mutagenesis
    Jay Tischfield; Fiscal Year: 2006
    ..6. To introduce DNA-PKcs deficiency to test whether or not Ku and DNA-PKcs participate in distinct as well as common DSB repair pathways. ..
  29. MINORITY PREDOCTORAL FELLOWSHIP PROGRAM
    BRENDA SALERNO; Fiscal Year: 2006
    ..This will facilitate the development of therapies for people with mutated NHEJ genes, and also anticancer treatments that can target NHEJ factors to sensitize cells before radiotherapy. ..
  30. DNA REPAIR AND RECOMBINATION FUNCTIONS OF SCID
    David Weaver; Fiscal Year: 1999
    ..With this information in hand he will then determine the mouse XRCC7 mutations. Other studies will show whether the XRCC7 mutant are null or missense mutants...
  31. CARCINOGENIC INTERACTIONS OF RADIATION AND CHEMICALS
    Robert Ullrich; Fiscal Year: 2007
    ..cytogenetic instability and Prkdc, the gene encoding the catalytic subunit of DNA dependent protein kinase (DNA PKcs)...
  32. ENZYMOLOGY OF DNA DOUBLE STRAND BREAK REJOINING
    William Morgan; Fiscal Year: 1999
    ..in DSB rejoining have not been fully identified; however, a number of proteins such as DNA polymerase, Ku and p350(DNA -pk) have been implicated in the reaction...
  33. Transgenic Mouse for DNA Damage Sensing and Signaling
    David Chen; Fiscal Year: 2005
    ..We propose to follow up these leads to obtain a clearer picture of the coordinating mechanisms between DNA-PK, ATM, and Nbs1. ..
  34. Effect of VDJ Recombination on Scid B Cell Development
    Yung Chang; Fiscal Year: 2007
    ..abstract_text> ..
  35. DNA POLYMERASES
    Stuart Linn; Fiscal Year: 1999
    ..The significance of pol epsilon being complexed to Ku protein will be studied and whether the p350 protein kinase (which forms the Ku-associated DNA dependent protein kinase) also complexes to pol epsilon will be ..
  36. Radiation-induced phosphorylation of DNA-PK at 2638/47
    Gregory Langland; Fiscal Year: 2005
    ..2) These sites will only be phosphorylated in G1 and early S phase and (3) the mutation of these sites will result in radiation sensitivity, an end-joining defect and a longer half-life of phospho-specific (ala) mutants at these sites. ..
  37. XRCC4 AND V<D>J RECOMBINATION AND DNA REPAIR
    KAREN FRANK; Fiscal Year: 2001
    ..e. Environment and Institutional Support: The training will take place in Dr. Alt's laboratory in the Enders Research Building of the Children's Hospital. ..
  38. A NEW ANIMAL MODEL OF SCID FOR BIOMEDICAL RESEARCH
    Katheryn Meek; Fiscal Year: 2006
    ..abstract_text> ..
  39. RISK FACTORS FOR ALCOHOLISM IN NATIVE AMERICANS
    Cindy Ehlers; Fiscal Year: 2006
    ..The identification of such variables may potentially be useful in the development of specific prevention and treatment programs for this population as well as other Native American tribes. ..
  40. Alcoholism risk and protective factors in Trinidad
    Cindy Ehlers; Fiscal Year: 2006
    ..Study findings can be compared to similar studies being conducted in the US. We believe these studies will allow for the identification of risk and protective factors for alcoholism in these islands. [unreadable] [unreadable]..
  41. ADOLESCENT MARIJUANA USE IN NATIVE AMERICANS
    Cindy Ehlers; Fiscal Year: 2008
    ..abstract_text> ..
  42. Translational Control of Radiation-Induced Apoptosis
    Benjamin Chen; Fiscal Year: 2005
    ..With regard to the approaches, ..
  43. Neurobehavioral Consequences of Adolescent Alcohol
    Cindy Ehlers; Fiscal Year: 2008
    ..AIM 3: To investigate the neurochemical substrates underlying the lasting neurobehavioral consequences of adolescent ethanol exposure, with a focus on NMDA systems ..
  44. PATHOGENESIS OF MURINE PARVOVIRUS FIELD STRAINS
    David Besselsen; Fiscal Year: 2007
    ..In addition, these studies will provide information about perturbations in host physiology and gene expression induced by murine parvoviruses, and basic scientific information about parvovirus host interaction. ..
  45. 5 NUCLEASE ASSAYS FOR RODENT HEALTH MONITORING
    David Besselsen; Fiscal Year: 2002
    ..FFPNA will greatly enhance the diagnostic capabilities for routine health monitoring of laboratory rodents and will provide a viable, cost-effective alternative for RAP testing. ..
  46. DNA REPAIR/V(D)J RECOMBINATION--FUNCTIONAL STUDY
    Guillermo Taccioli; Fiscal Year: 2001
    ....
  47. GENE LINKAGE STUDY OF IMMUNODEFICIENCY IN NAVAJO INDIANS
    Morton Cowan; Fiscal Year: 2001
    ..The results of this study will lead to better understanding of the maturation of T and B cell immunity and novel approaches to manipulating the immune system as well as more specific agents for treating certain malignancies. ..
  48. TOLERANCE POST IN UTERO TRANSPLANTATION
    Morton Cowan; Fiscal Year: 2005
    ....
  49. OXIDATIVE STRESS, APOPTOSIS AND DRUG RESISTANCE
    Istvan Boldogh; Fiscal Year: 2003
    ..abstract_text> ..
  50. Laser Capture Microscopy and 2D-DIGE: Cancer Proteomics
    William Dynan; Fiscal Year: 2007
    ..In the next phase, broader clinical utility will be demonstrated using a larger sample set. Changes in the pattern of protein expression will be identified. These changes can serve as clinically useful markers of tumor progression. ..
  51. Chromosome X and Ovarian Development
    ANN DORWARD; Fiscal Year: 2007
    ..unreadable] [unreadable]..
  52. Mechanism of Meclp in the Checkpoint Response
    GEORGE BRUSH; Fiscal Year: 2006
    ..It is expected that these studies will provide significant insight into the molecular mechanisms underlying maintenance of the non-cancerous state under genotoxic conditions. ..
  53. GENETIC VARIATION IN HUMAN NHEJ DNA REPAIR GENES
    Carl Anderson; Fiscal Year: 2005
    ..This study also will provide a moderately dense set of mapped polymorphic markers within the five know NHEJ genes for subsequence linkage studies that could reveal subtle effects and more complex allele interactions. ..
  54. Tyrosyl-DNA phosphodiesterase and oxidative DNA damage
    Lawrence Povirk; Fiscal Year: 2008
    ..These studies are intended to clarify the mechanism by which Tdp1 deficiency leads to SCAN1, and may also help elucidate the role of oxidative stress in various other neurological disorders, cancer and aging. ..
  55. Mouse Models of Tumor Progression and Therapy Response
    CHRISTOPHER KEMP; Fiscal Year: 2007
    ..These experiments will reveal the molecular and cellular basis for the poor clinical outcome associated with p27 deficient tumors. This knowledge can then be applied to improve treatment design and regimen in the clinical setting. ..
  56. Mechanism of DNA Damage Recognition in Higher Eukaryotes
    Suk Hee Lee; Fiscal Year: 2005
    ..Various mutants of damage recognition factors (RPA and XPC) will be used to examine any unique role these proteins possess in 3' and 5' incising. ..
  57. Methods in Protein Structure Analysis 2004
    Carl Anderson; Fiscal Year: 2004
    ..The overall aim is to provide a forum for exchanging the latest methods and ideas in protein structure analysis and proteomics to current and future practitioners. ..
  58. EGFR/Radiation Response and Resistance Interactions
    Paul M Harari; Fiscal Year: 2010
    ..In this research proposal, we seek to increase the percentage of cancer patients who benefit from leading cancer drugs through the identification and disabling of specific tumor cell molecules that promote treatment resistance. ..
  59. Typhoon 9410 Gel/Blot Imager
    OLIVER SEMMES; Fiscal Year: 2004
    ..Additionally, several investigators will be able to undertake new avenues of investigation using the Typhoon's features. ..
  60. HUMAN V(D)J RECOMBINASE IN NEOPLASTIC AND PRIMARY CELLS
    Michael Lieber; Fiscal Year: 2004
    ..Corresponding studies of such regions on minichromosomes will permit the testing of the effects of the direction of DNA replication and transcription. ..
  61. Anti-inflammatory Serpin(AAT and Elafin) Gene Transfers*
    Sihong Song; Fiscal Year: 2003
    ..abstract_text> ..
  62. Targeted Alpha-Particle Emitter Therapy of Metastases
    George Sgouros; Fiscal Year: 2009
    ..The work described in this application is intended to develop and evaluate such an approach. ..
  63. MODELING AND DOSIMETRY FOR RADIOLABELED ANTIBODY THERAPY
    George Sgouros; Fiscal Year: 2002
    ....
  64. Gene Therapy for Correction of PiZ Mutation
    Sihong Song; Fiscal Year: 2006
    ..Liver pathology will be examined. We anticipate achieving the therapeutic correction in PiZ transgenic mouse model. The success of this project may lead to a novel gene therapy for clinical treatment of human AAT deficiency. ..
  65. The Role of Double Strand Breaks in Carcinogenesis
    CHRISTOPHER KEMP; Fiscal Year: 2006
    ..p53 response pathway in genetic mutants of putative upstream regulators of p53, notably the P13K family members DNAPK and Atm...
  66. INTERACTIONS OF DNA-PK WITH THE TRANSCRIPTION APPARATUS
    William Dynan; Fiscal Year: 2004
    ..Experiments in this proposal will provide definitive information about signaling interactions that occur between DNA-PK and the transcription apparatus. ..
  67. Biochemical Basis of CENP-A Epigenetic Inheritance
    SAMANTHA ZEITLIN; Fiscal Year: 2005
    ..These studies will also have direct implications for understanding cancer causation, and applications in gene therapy. ..