MMSL 2012, 81(4):177-187 | DOI: 10.31482/mmsl.2012.025

PHOSPHATIDYLINOSITOL-3-KINASE RELATED KINASES (PIKKS) IN RADIATION-INDUCED DNA DAMAGEReview article

Aleš Tichý ORCID...1, Kamila Ďurišová1, Eva Novotná1, Lenka Zárybnická ORCID...1, Jiřina Vávrová1, Jaroslav Pejchal ORCID...2, Zuzana Šinkorová ORCID...1*
1 Department of Radiobiology, Faculty of Health Sciences in Hradec Králové, University of Defence in Brno, Czech Republic
2 Centrum of Advanced Studies, Faculty of Health Sciences in Hradec Králové, University of Defence in Brno, Czech Republic.

This review describes a drug target for cancer therapy, family of phosphatidylinositol-3 kinase related kinases (PIKKs), and it gives a comprehensive review of recent information. Besides general information about phosphatidylinositol-3 kinase superfamily, it characterizes a DNA-damage response pathway since it is monitored by PIKKs.

Keywords: PIKKs; ATM; ATR; DNA-PK; Ionising radiation; DNA-repair

Received: September 5, 2012; Revised: November 27, 2012; Published: December 7, 2012  Show citation

ACS AIP APA ASA Harvard Chicago Chicago Notes IEEE ISO690 MLA NLM Turabian Vancouver
Tichý, A., Ďurišová, K., Novotná, E., Zárybnická, L., Vávrová, J., Pejchal, J., & Šinkorová, Z. (2012). PHOSPHATIDYLINOSITOL-3-KINASE RELATED KINASES (PIKKS) IN RADIATION-INDUCED DNA DAMAGE. MMSL, 81(4), 177-187. doi: 10.31482/mmsl.2012.025
Share...
Download citation
  • BibTeX (.bib)
  • Bookends (.ris)
  • EasyBib (.ris)
  • EndNote (.enw)
  • EndNote 8 (.xml)
  • ISI WoS (.isi)
  • Medlars (.medlars)
  • Mendeley (.ris)
  • MODS (.xml)
  • Papers (.ris)
  • RefWorks (.txt)
  • RefManager (.ris)
  • RIS (.ris)
  • MS Word (.xml)
  • Zotero (.ris)
    • Open full article

    References

    1. Boran AD, Seco J, Jayaraman V, et al. A potential Peptide therapeutic derived from the juxtamembrane domain of the epidermal growth factor receptor. PLoS One. 2012,7, e49702. Go to original source... Go to PubMed...
    2. Clark J, Cools J, Gilliland DG. EGFR inhibition in non-small cell lung cancer: resistance, once again, rears its ugly head. PLoS Med. 2005, 2, e75. Go to original source... Go to PubMed...
    3. Glaser KB, Li J, Marcotte PA, et al. Preclinical Characterization of ABT-348, a Kinase Inhibitor Targeting the Aurora, Vascular Endothelial Growth Factor Receptor/Platelet-Derived Growth Factor Receptor, and Src Kinase Families. J Pharmacol Exp Ther. 2012, 343, 617-27. Go to original source... Go to PubMed...
    4. Whitman M, Kaplan DR, Schaffhausen B, et al. Association of phosphatidylinositol kinase activity with polyoma middle-T competent for transformation. Nature. 1985, 315, 239-242. Go to original source... Go to PubMed...
    5. Whitman M, Downes CP, Keeler M, et al. Type I phosphatidylinositol kinase makes a novel inositol phospholipid, phosphatidylinositol-3-phosphate. Nature 1988, 332, 644-646. Go to original source... Go to PubMed...
    6. Brachmann SM, Yballe CM, Innocenti M, et al. Role of phosphoinositide 3-kinase regulatory isoforms in development and actin rearrangement. Mol Cell Biol. 2005, Apr 25(7), 2593-606. Go to original source... Go to PubMed...
    7. Pollard TD, Earnshaw WC. Protein kinases. In: Cell biology. Philadelphia: Sander, Elsevier Science, 2002, 425-429.
    8. Hawkins PT, Anderson KE, Davidson K, et al. Signalling through Class I PI3Ks in mammalian cells. Biochem Soc Trans. 2006, 34, 647-62. Go to original source... Go to PubMed...
    9. Backer JM. The regulation and function of Class III PI3Ks: novel roles for Vps34. Biochem J. 2008, 410, 1-17. Go to original source... Go to PubMed...
    10. Falck J, Coates J, Jackson SP. Conserved modes of recruitment of ATM, ATR and DNA-PKcs to sites of DNA damage. Nature 2005;434:605-611. Go to original source... Go to PubMed...
    11. Lavin MF, Kozlov S, Gueven N, Peng C, Birrell G, Chen P, Scott S. Atm and cellular response to DNA damage. Adv Exp Med Biol. 2005, 570, 457-476. Go to original source... Go to PubMed...
    12. Tichý A, Vávrová J, Pejchal J, et al. Ataxia-telangiectasia mutated kinase (ATM) as a central regulator of radiation-induced DNA damage response. Acta Medica (Hradec Kralove) 2010, 53, 13-17. Review Go to original source... Go to PubMed...
    13. Khanna KK, Lavin MF, Jackson SP, et al. ATM, a central controller of cellular responses to DNA damage. Cell Death Differ. 2001, 8, 1052-1065. Review. Go to original source... Go to PubMed...
    14. Bakkenist C, Kastan MB. DNA damage activates ATM through intermolecular autophosphorylation and dimmer dissociation. Nature. 2003, 421, 499-506. Go to original source... Go to PubMed...
    15. Uziel T, Lerenthal Y, Moyal L, et al. Requirement of the MRN complex for ATM activation by DNA damage. EMBO J. 2003, 22, 5612-5621. Go to original source... Go to PubMed...
    16. Lavin MF. The Mre11 complex and ATM: a two-way functional interaction in recognising and signalling DNA double strand breaks. DNA Repair (Amst) 2004;3:1515-1520. Go to original source... Go to PubMed...
    17. Lee JH, Paull TT. ATM activation by DNA double-strand breaks through the Mre11-Rad50-Nbs1 complex. Science. 2005, 308, 551-554.
    18. Löbrich M, Jeggo PA. The two edges of the ATM sword: co-operation between repair and checkpoint functions. Radiother Oncol. 2005, 76, 112-118. Review. Go to original source... Go to PubMed...
    19. Vannier JB, Depeiges A, White C, et al. Two roles for Rad50 in telomere maintenance. EMBO J. 2006, 25, 4577-4585. Go to original source... Go to PubMed...
    20. Ghosal G, Muniyappa K. The Characterization of Saccharomyces cerevisiae Mre11/Rad50/Xrs2 Complex Reveals that Rad50 Negatively Regulates Mre11 Endonucleolytic but not the Exonucleolytic Activity. J Mol Biol. 2007, 372, 864-882. Go to original source... Go to PubMed...
    21. Stiff T, O'Driscoll M, Rief N, et al. ATM and DNA-PK function redundantly to phosphorylate H2AX after exposure to ionising radiation. Cancer Res. 2004, 64, 2390-2396. Go to original source... Go to PubMed...
    22. Rogakou EP, Boon C, Redon C, et al. Megabase chromatin domains involved in DNA double-strand breaks in vivo. J Cell Biol. 1999, 146, 905-916. Go to original source... Go to PubMed...
    23. Havelek R, Řezáčová M, Šinkorová Z, et al. Phosphorylation of histone H2AX as an indicator of received dose of gamma radiation after whole-body irradiation of rats. Acta Vet. Brno. 2011, 80, 113-118. Go to original source...
    24. Bassing CH, Chua KF, Sekiguchi J, et al. Increased ionising radiation sensitivity and genomic instability in the absence of histone H2AX. Proc Natl Acad Sci. 2002, 99, 8173-8178. Go to original source... Go to PubMed...
    25. Celeste A, Petersen S, Romanienko PJ, et al. Genomic instability in mice lacking histone H2AX. Science. 2002, 296, 922-927. Go to original source... Go to PubMed...
    26. Sengupta S, Harris CC. p53: traffic cop at the crossroads of DNA repair and recombination. Nat Rev Mol Cell Biol. 2005, 6, 44-55. Go to original source... Go to PubMed...
    27. Hanel W, Moll UM. Links between mutant p53 and genomic instability.
    28. Vogelstein B, Lane D, Levine AJ. Surfing the p53 network. Nature. 2000, 408, 307-310. Go to original source... Go to PubMed...
    29. Criswell T, Leskov K, Miyamoto S, et al. Transcription factors activated in mammalian cells after clinically relevant doses of ionising radiation. Oncogene. 2003, 22, 5813-5827. Go to original source... Go to PubMed...
    30. Maya R, Balass M, Kim ST, et al. ATM-dependent phosphorylation of Mdm2 on serine 395: Role in p53 activation by DNA damage. Genes Dev. 2001, 15, 1067-1077. Go to original source... Go to PubMed...
    31. Michael D, Oren M. The p53-Mdm2 module and the ubiquitin system. Semin Cancer Biol. 2003, 13, 49-58. Review. Go to original source... Go to PubMed...
    32. Matsuoka S, Rotman G, Ogawa A, et al. Ataxia telangiectasia-mutated phosphorylates Chk2 in vivo and in vitro. Proc Natl Acad Sci USA. 2000, 97, 10389-10394. Go to original source... Go to PubMed...
    33. Tichý A, Záškodová D, Vávrová J, et al. Gamma-radiation-induced ATM-dependent signalling in human T-lymphocyte leukemic cells, MOLT-4. Acta Biochim Pol. 2007, 54, 281-287. Go to original source... Go to PubMed...
    34. Tichý A, Záskodová D, Zoelzer F, et al. Gamma-radiation-induced phosphorylation of p53 on serine 15 is dose-dependent in MOLT-4 leukaemia cells. Folia Biol (Praha). 2009, 55, 41-44. Go to PubMed...
    35. Schwartz GK. CDK inhibitors: cell cycle arrest versus apoptosis. Cell Cycle. 2002, 1, 122-123. Go to original source... Go to PubMed...
    36. Falck J, Mailand N, Syljuasen RG, et al. The ATM-Chk2-Cdc25A checkpoint pathway guards against radioresistant DNA synthesis. Nature. 2001, 410, 842-847. Go to original source... Go to PubMed...
    37. Falck J, Petrini JH, Williams BR, et al. The DNA damage-dependent intra-S phase checkpoint is regulated by parallel pathways. Nat Genet. 2002, 30, 290-294. Go to original source... Go to PubMed...
    38. Lukas J, Lukas C, Bartek J. Mammalian cell cycle checkpoints: signalling pathways and their organization in space and time. DNA Repair (Amst) 2004, 3, 997-1007. Review. Go to original source... Go to PubMed...
    39. Mahaney BL, Meek K, Lees-Miller SP. Repair of ionising radiation-induced DNA double-strand breaks by non-homologous end-joining. Biochem J. 2009, 417, 639-650. Review. Go to original source... Go to PubMed...
    40. Kasparek TR, Humphrey TC. DNA double-strand break repair pathways, chromosomal rearrangements and cancer. Semin Cell Dev Biol. 2011, 22, 886-897. Go to original source... Go to PubMed...
    41. Gottlieb TM, Jackson SP. The DNA-dependent protein kinase: requirement for DNA ends and association with Ku antigen. Cell. 1993, 72, 131-142. Go to original source... Go to PubMed...
    42. Matsumoto Y, Suzuki N, Namba N, et al. Cleavage and phosphorylation of XRCC4 protein induced by X-irradiation. FEBS Lett. 2000, 478, 67-71. Go to original source... Go to PubMed...
    43. Grawunder U, Wilm M, Wu X, et al. Activity of DNA ligase IV stimulated by complex formation with XRCC4 protein in mammalian cells. Nature. 1997, 388, 492-495. Go to original source... Go to PubMed...
    44. Barnes DE, Stamp G, Rosewell I, et al. Targeted disruption of the gene encoding DNA ligase IV leads to lethality in embryonic mice. Curr Biol. 1998, 8, 1395-1398. Go to original source... Go to PubMed...
    45. Riballo E, Critchlow SE, Teo SH, et al. Identification of a defect in DNA ligase IV in a radiosensitive leukaemia patient. Curr Biol. 1999, 9, 699-702. Go to original source... Go to PubMed...
    46. Bogue MA, Jhappan C, Roth DB. Analysis of variable (diversity) joining recombination in DNA-dependent protein kinase (DNA-PK)-deficient mice reveals DNA-PK independent pathways for both signal and coding joint formation. Proc Nat Acad Sci USA. 1998, 95, 15559-15564. Go to original source... Go to PubMed...
    47. Van der Burg M, van Dongen JJ, van Gent DC. DNA-PKcs deficiency in human: long predicted, finally found. Curr Opin Allergy Cl. 2009, 9, 503-509. Go to original source... Go to PubMed...
    48. Kim ST, Lim DS, Canman CE, et al. Substrate specificities and identification of putative substrates of ATM kinase family members. J Biol Chem. 1999, 274, 37538-37543. Go to original source... Go to PubMed...
    49. Douglas P, Sapkota GP, Morrice N, et al. Identification of in vitro and in vivo phosphorylation sites in the catalytic subunit of the DNA-dependent protein kinase. Biochem J. 2002, 368, 243-251. Go to original source... Go to PubMed...
    50. Hammel M, Yu Y, Mahaney BL et al. Ku and DNA-dependent protein kinase dynamic conformations and assembly regulate DNA binding and the initial non-homologous end joining complex. J Biol Chem. 2010, 285, 1414-1423. Go to original source... Go to PubMed...
    51. Hill R, Lee PWK. The DNA-dependent protein kinase (DNA-PK): More than just a case of making ends meet? Cell Cycle. 2010, 9, 3460-3469. Go to original source... Go to PubMed...
    52. Shiloh Y. ATM and related protein kinases: safeguarding genome integrity. Nat Rev Cancer. 2003, 3, 155-168. Review. Go to original source... Go to PubMed...
    53. Cimprich KA. Probing ATR activation with model DNA templates. Cell Cycle. 2007, 6, 2348-2354. Go to original source... Go to PubMed...
    54. Cortez D, Guntuku S, Qin J, et al. ATR and ATRIP: partners in checkpoint signalling. Science. 2001, 294, 1713-1716. Go to original source... Go to PubMed...
    55. Fanning E, Klimovich V, Nager AR. A dynamic model for replication protein A (RPA) function in DNA processing pathways. Nucleic Acids Res. 2006, 34, 4126-37. Go to original source... Go to PubMed...
    56. Mäkiniemi M, Hillukkala T, Tuusa J, et al. BRCT domain-containing protein TopBP1 functions in DNA replication and damage response. J Biol Chem. 2012, 276, 30399-30406.
    57. Kumagai A, Lee J, Yoo HY, Dunphy WG. TopBP1 activates the ATR-ATRIP complex. Cell. 2006, 124, 943-955. Go to original source... Go to PubMed...
    58. Nam EA, Cortez D. ATR signalling: more than meeting at the fork. Biochem J. 2011, 436, 527-536. Go to original source... Go to PubMed...
    59. Cimprich KA, Cortez D. ATR: an essential regulator of genome integrity. Nat Rev Mol Cell Biol. 2008, 9, 616-27. Go to original source... Go to PubMed...
    60. Prevo R, Fokas E, Reaper PM et al. The novel ATR inhibitor VE-821 increases sensitivity of pancreatic cancer cells to radiation and chemotherapy. Cancer Biol Ther. 2012, 13, 1072-81. Go to original source... Go to PubMed...
    61. Pires IM, Olcina MM, Anbalagan S et al. Targeting radiation-resistant hypoxic tumour cells through ATR inhibition. Br J Cancer. 2012, 107, 291-299. Go to original source... Go to PubMed...
    62. Yoo HY, Kumagai A, Shevchenko A, et al. Ataxia-telangiectasia mutated (ATM)-dependent activation of ATR occurs through phosphorylation of TopBP1 by ATM. J Biol Chem. 2007, 282, 17501-17506. Go to original source... Go to PubMed...
    63. Smith J, Tho LM, Xu N, et al. The ATM-Chk2 and ATR-Chk1 pathways in DNA damage signaling and cancer. Adv Cancer Res. 2010, 108, 73-112. Go to original source... Go to PubMed...
    64. Hay N, Sonenberg N. Upstream and downstream of mTOR. Genes Dev. 2004, 18, 1926-1945. Go to original source... Go to PubMed...
    65. Mita MM, Mita A, Rowinsky EK. The molecular target of rapamycin (mTOR) as a therapeutic target against cancer. Cancer Biol Ther. 2003, 2, S169-177. Review. Go to original source...
    66. Datta SR, Dudek H, Tao X, et al. Akt phosphorylation of BAD couples survival signals to the cell-intrinsic death machinery. Cell. 1997, 91, 231-241. Go to original source... Go to PubMed...
    67. Raught B, Gingras AC, Sonenberg N. The target of rapamycin (TOR) proteins. Proc Natl Acad Sci USA. 2001, 98, 7037-7044. Go to original source... Go to PubMed...
    68. Eshleman JS, Carlson BL, Mladek AC, et al. Inhibition of the mammalian target of rapamycin sensitizes U87 xenografts to fractionated radiation therapy. Cancer Res. 2002, 62, 7291-7297.
    69. Sarbassov D, Ali S, Kim D, et al. Rictor, a novel binding partner of mTOR, defines a rapamycin-insensitive and raptor-independent pathway that regulates the cytoskeleton". Curr Biol. 2004, 14, 1296-1302. Go to original source... Go to PubMed...
    70. Huang S, Houghton PJ. Targeting mTOR signaling for cancer therapy. Curr Opin Pharmacol. 2003, 3, 371-377. Go to original source... Go to PubMed...
    71. Schiewer MJ, Den R, Hoang DT, et al. mTOR is a selective effector of the radiation therapy response in androgen receptor-positive prostate cancer. Endocr Relat Cancer. 2012, 19, 1-12. Go to original source... Go to PubMed...
    72. Le Guezennec X, Brichkina A, Huang YF, et al. Wip1-dependent regulation of autophagy, obesity, and atherosclerosis. Cell Metab. 2012, 16, 68-80. Go to original source... Go to PubMed...
    73. Chen H, Ma Z, Vanderwaal RP et al. The mTOR inhibitor rapamycin suppresses DNA double-strand break repair. Radiat Res. 2011, 175, 214-224. Go to original source... Go to PubMed...
    74. Robert T, Vanoli F, Chiolo I, et al. HDACs link the DNA damage response, processing of double-strand breaks and autophagy. Nature. 2011, 471, 74-79. Go to original source... Go to PubMed...
    75. Clerici M, Mantiero D, Lucchini G, et al. The Saccharomyces cerevisiae Sae2 protein negatively regulates DNA damage checkpoint signalling. EMBO Rep. 2006, 7, 212-218. Go to original source... Go to PubMed...
    76. Herceg Z, Hulla W, Gell D, et al. Disruption of Trrap causes early embryonic lethality and defects in cell cycle progression. Nat Genet. 2001, 29, 206-211. Go to original source... Go to PubMed...
    77. Herceg Z, Wang ZQ. Rendez-vous at mitosis: TRRAPed in the chromatin. Cell Cycle. 2005, 4, 383-387. Go to original source... Go to PubMed...
    78. Yamashita A, Kashima I, Ohno S. The role of SMG-1 in nonsense-mediated mRNA decay. Biochim Biophys Acta. 2005, 1754, 305-315. Go to original source... Go to PubMed...
    79. Jaboin JJ, Shinohara ET, Moretti L, Yang et al. The role of mTOR inhibition in augmenting radiation induced autophagy. Technol Cancer Res Treat. 2007, 6, 443-447. Go to original source... Go to PubMed...
    80. Murr R, Vaissière T, Sawan C, et al. Orchestration of chromatin-based processes: mind the TRRAP. Oncogene. 2007, 26, 5358-5372. Go to original source... Go to PubMed...
    81. Shuttleworth SJ, Silva FA, Cecil AR, et al. Progress in the preclinical discovery and clinical development of class I and dual class I/IV phosphoinositide 3-kinase (PI3K) inhibitors. Curr Med Chem. 2011, 18, 2686-2714. Go to original source... Go to PubMed...
    82. Hurley PJ, Bunz F. ATM and ATR: components of an integrated circuit. Cell Cycle. 2007, 6, 414-417. Review. Go to original source... Go to PubMed...
    83. Tomita M. Involvement of DNA-PK and ATM in radiation- and heat-induced DNA damage recognition and apoptotic cell death. Radiat Res. 2010, 51, 493-501. Go to original source... Go to PubMed...

    Return to the content