Advertisement

ATM: Its Recruitment, Activation, Signalling and Contribution to Tumour Suppression

  • Atsushi Shibata
  • Penny Jeggo
Chapter
Part of the Cancer Drug Discovery and Development book series (CDD&D)

Abstract

DNA double strand breaks (DSBs) are a critical lesion for cancer etiology. Most cancer cells incur increased DNA breakage to enhance genomic instability. The DSB damage response encompasses pathways of repair and a signal transduction pathway. The ataxia telangiectasia mutated (ATM) kinase lies at the centre of the signalling response. ATM is not essential for the major DSB repair process in mammalian cells but influences DSB repair, including its accuracy, in multiple ways. ATM is activated by DSBs to promote cell cycle checkpoint arrest and apoptosis. There is mounting evidence that ATM is active endogenously and/or that it can be activated by non-DSB routes, including oxidative damage. It plays an important role in regulating cellular redox status. The tumour suppressor functions of ATM are discussed. Paradoxically, since elevated DSBs arise in cancer cells, despite being a tumour suppressor, pharmacological inhibition of ATM is a promising route for cancer therapy.

Keywords

DNA damage signalling Radiosensitivity DNA double-strand break repair Cell cycle checkpoints Apoptosis Ataxia telangiectasia 

References

  1. Alagoz M, Katsuki Y, Ogiwara H, Ogi T, Shibata A, Kakarougkas A, Jeggo P (2015) SETDB1, HP1 and SUV39 promote repositioning of 53BP1 to extend resection during homologous recombination in G2 cells. Nucleic Acids Res 43:7931–7944PubMedPubMedCentralCrossRefGoogle Scholar
  2. Alatwi HE, Downs JA (2015) Removal of H2A.Z by INO80 promotes homologous recombination. EMBO Rep 16:986–994PubMedPubMedCentralCrossRefGoogle Scholar
  3. Albarakati N, Abdel-Fatah TM, Doherty R, Russell R, Agarwal D, Moseley P, Perry C, Arora A, Alsubhi N, Seedhouse C et al (2015) Targeting BRCA1-BER deficient breast cancer by ATM or DNA-PKcs blockade either alone or in combination with cisplatin for personalized therapy. Mol Oncol 9:204–217PubMedCrossRefPubMedCentralGoogle Scholar
  4. Ayrapetov MK, Gursoy-Yuzugullu O, Xu C, Xu Y, Price BD (2014) DNA double-strand breaks promote methylation of histone H3 on lysine 9 and transient formation of repressive chromatin. Proc Natl Acad Sci U S A 111:9169–9174PubMedPubMedCentralCrossRefGoogle Scholar
  5. Bakkenist CJ, Kastan MB (2003) DNA damage activates ATM through intermolecular autophosphorylation and dimer dissociation. Nature 421:499–506PubMedPubMedCentralCrossRefGoogle Scholar
  6. Bakkenist CJ, Kastan MB (2015) Chromatin perturbations during the DNA damage response in higher eukaryotes. DNA Repair 36:8–12PubMedPubMedCentralCrossRefGoogle Scholar
  7. Baldeyron C, Soria G, Roche D, Cook AJ, Almouzni G (2011) HP1alpha recruitment to DNA damage by p150CAF-1 promotes homologous recombination repair. J Cell Biol 193:81–95PubMedPubMedCentralCrossRefGoogle Scholar
  8. Barazzuol L, Rickett N, Ju L, Jeggo PA (2015) Low levels of endogenous or X-ray-induced DNA double-strand breaks activate apoptosis in adult neural stem cells. J Cell Sci 128:3597–3606PubMedPubMedCentralCrossRefGoogle Scholar
  9. Bartek J, Lukas J (2001) Pathways governing G1/S transition and their response to DNA damage. FEBS Lett 490:117–122PubMedCrossRefPubMedCentralGoogle Scholar
  10. Bartek J, Lukas J (2007) DNA damage checkpoints: from initiation to recovery or adaptation. Curr Opin Cell Biol 19:238–245PubMedCrossRefPubMedCentralGoogle Scholar
  11. Bartek J, Lukas C, Lukas J (2004) Checking on DNA damage in S phase. Nat Rev Mol Cell Biol 5:792–804PubMedPubMedCentralCrossRefGoogle Scholar
  12. Barzilai A, Rotman G, Shiloh Y (2002) ATM deficiency and oxidative stress: a new dimension of defective response to DNA damage. DNA Repair 1:3–25PubMedCrossRefPubMedCentralGoogle Scholar
  13. Beamish H, Lavin MF (1994) Radiosensitivity in ataxia-telangiectasia: anomalies in radiation-induced cell cycle delay. Int J Radiat Biol 65:175–184PubMedPubMedCentralCrossRefGoogle Scholar
  14. Berkovich E, Monnat RJ Jr, Kastan MB (2007) Roles of ATM and NBS1 in chromatin structure modulation and DNA double-strand break repair. Nat Cell Biol 9:683–690PubMedPubMedCentralCrossRefGoogle Scholar
  15. Beucher A, Birraux J, Tchouandong L, Barton O, Shibata A, Conrad S, Goodarzi AA, Krempler A, Jeggo PA, Lobrich M (2009) ATM and Artemis promote homologous recombination of radiation-induced DNA double-strand breaks in G2. EMBO J 28:3413–3427PubMedPubMedCentralCrossRefGoogle Scholar
  16. Bhoumik A, Singha N, O’Connell MJ, Ronai ZA (2008) Regulation of TIP60 by ATF2 modulates ATM activation. J Biol Chem 283:17605–17614PubMedPubMedCentralCrossRefGoogle Scholar
  17. Biehs R, Steinlage M, Barton O, Juhasz S, Kunzel J, Spies J, Shibata A, Jeggo PA, Lobrich M (2017) DNA double-strand break resection occurs during non-homologous end joining in G1 but is distinct from resection during homologous recombination. Mol Cell 65:671–684.e5PubMedPubMedCentralCrossRefGoogle Scholar
  18. Burgess RC, Burman B, Kruhlak MJ, Misteli T (2014) Activation of DNA damage response signaling by condensed chromatin. Cell Rep 9:1703–1717PubMedPubMedCentralCrossRefGoogle Scholar
  19. Celeste A, Petersen S, Romanienko PJ, Fernandez-Capetillo O, Chen HT, Sedelnikova OA, Reina-San-Martin B, Coppola V, Meffre E, Difilippantonio MJ et al (2002) Genomic instability in mice lacking histone H2AX. Science 296:922–927PubMedPubMedCentralCrossRefGoogle Scholar
  20. Clouaire T, Legube G (2015) DNA double strand break repair pathway choice: a chromatin based decision? Nucleus 6:107–113PubMedPubMedCentralCrossRefGoogle Scholar
  21. Cornforth MN, Bedford JS (1985) On the nature of a defect in cells from individuals with ataxia-telangiectasia. Science 227:1589–1591PubMedPubMedCentralCrossRefGoogle Scholar
  22. Cosentino C, Grieco D, Costanzo V (2011) ATM activates the pentose phosphate pathway promoting anti-oxidant defence and DNA repair. EMBO J 30:546–555PubMedCrossRefPubMedCentralGoogle Scholar
  23. Daniel JA, Pellegrini M, Lee JH, Paull TT, Feigenbaum L, Nussenzweig A (2008) Multiple autophosphorylation sites are dispensable for murine ATM activation in vivo. J Cell Biol 183:777–783PubMedPubMedCentralCrossRefGoogle Scholar
  24. Deckbar D, Birraux J, Krempler A, Tchouandong L, Beucher A, Walker S, Stiff T, Jeggo P, Lobrich M (2007) Chromosome breakage after G2 checkpoint release. J Cell Biol 176:749–755PubMedPubMedCentralCrossRefGoogle Scholar
  25. Deckbar D, Stiff T, Koch B, Reis C, Lobrich M, Jeggo PA (2010) The limitations of the G1-S checkpoint. Cancer Res 70:4412–4421PubMedCrossRefPubMedCentralGoogle Scholar
  26. Deckbar D, Jeggo PA, Lobrich M (2011) Understanding the limitations of radiation-induced cell cycle checkpoints. Crit Rev Biochem Mol Biol 46:271–283PubMedPubMedCentralCrossRefGoogle Scholar
  27. Du F, Zhang M, Li X, Yang C, Meng H, Wang D, Chang S, Xu Y, Price B, Sun Y (2014) Dimer monomer transition and dimer re-formation play important role for ATM cellular function during DNA repair. Biochem Biophys Res Commun 452:1034–1039PubMedPubMedCentralCrossRefGoogle Scholar
  28. Eaton JS, Lin ZP, Sartorelli AC, Bonawitz ND, Shadel GS (2007) Ataxia-telangiectasia mutated kinase regulates ribonucleotide reductase and mitochondrial homeostasis. J Clin Invest 117:2723–2734PubMedPubMedCentralCrossRefGoogle Scholar
  29. Falck J, Mailand N, Syljuasen RG, Bartek J, Lukas J (2001) The ATM-Chk2-Cdc25A checkpoint pathway guards against radioresistant DNA synthesis. Nature 410:842–847PubMedPubMedCentralCrossRefGoogle Scholar
  30. Falck J, Petrini JH, Williams BR, Lukas J, Bartek J (2002) The DNA damage-dependent intra-S phase checkpoint is regulated by parallel pathways. Nat Genet 30:290–294PubMedCrossRefPubMedCentralGoogle Scholar
  31. Falck J, Coates J, Jackson SP (2005) Conserved modes of recruitment of ATM, ATR and DNA-PKcs to sites of DNA damage. Nature 434:605–611PubMedCrossRefPubMedCentralGoogle Scholar
  32. Fradet-Turcotte A, Canny MD, Escribano-Diaz C, Orthwein A, Leung CC, Huang H, Landry MC, Kitevski-LeBlanc J, Noordermeer SM, Sicheri F et al (2013) 53BP1 is a reader of the DNA-damage-induced H2A Lys 15 ubiquitin mark. Nature 499:50–54PubMedPubMedCentralCrossRefGoogle Scholar
  33. Fugger K, Mistrik M, Neelsen KJ, Yao Q, Zellweger R, Kousholt AN, Haahr P, Chu WK, Bartek J, Lopes M et al (2015) FBH1 catalyzes regression of stalled replication forks. Cell Rep.  https://doi.org/10.1016/j.celrep.2015.02.028
  34. Goldberg M, Stucki M, Falck J, D’Amours D, Rahman D, Pappin D, Bartek J, Jackson SP (2003) MDC1 is required for the intra-S-phase DNA damage checkpoint. Nature 421:952–956PubMedCrossRefPubMedCentralGoogle Scholar
  35. Grinthal A, Adamovic I, Weiner B, Karplus M, Kleckner N (2010) PR65, the HEAT-repeat scaffold of phosphatase PP2A, is an elastic connector that links force and catalysis. Proc Natl Acad Sci U S A 107:2467–2472PubMedPubMedCentralCrossRefGoogle Scholar
  36. Grosjean-Raillard J, Tailler M, Ades L, Perfettini JL, Fabre C, Braun T, De Botton S, Fenaux P, Kroemer G (2009) ATM mediates constitutive NF-kappaB activation in high-risk myelodysplastic syndrome and acute myeloid leukemia. Oncogene 28:1099–1109PubMedCrossRefGoogle Scholar
  37. Guo Z, Kozlov S, Lavin MF, Person MD, Paull TT (2010) ATM activation by oxidative stress. Science 330:517–521PubMedCrossRefGoogle Scholar
  38. Huen MS, Grant R, Manke I, Minn K, Yu X, Yaffe MB, Chen J (2007) RNF8 transduces the DNA-damage signal via histone ubiquitylation and checkpoint protein assembly. Cell 131:901–914PubMedPubMedCentralCrossRefGoogle Scholar
  39. Ijiri K, Potten CS (1986) Radiation-hypersensitive cells in small intestinal crypts; their relationships to clonogenic cells. Br J Cancer Suppl 7:20–22PubMedPubMedCentralGoogle Scholar
  40. Insinga A, Cicalese A, Faretta M, Gallo B, Albano L, Ronzoni S, Furia L, Viale A, Pelicci PG (2013) DNA damage in stem cells activates p21, inhibits p53, and induces symmetric self-renewing divisions. Proc Natl Acad Sci U S A 110:3931–3936PubMedPubMedCentralCrossRefGoogle Scholar
  41. International Nijmegen Breakage Syndrome Study Group (2000) Nijmegen breakage syndrome. The International Nijmegen Breakage Syndrome Study Group. Arch Dis Child 82:400–406CrossRefGoogle Scholar
  42. Jasin M, Rothstein R (2013) Repair of strand breaks by homologous recombination. Cold Spring Harb Perspect Biol 5:a012740PubMedPubMedCentralCrossRefGoogle Scholar
  43. Jeggo PA, Downs JA (2014) Roles of chromatin remodellers in DNA double strand break repair. Exp Cell Res 329:69–77PubMedCrossRefPubMedCentralGoogle Scholar
  44. Jeggo PA, Lobrich M (2015) How cancer cells hijack DNA double-strand break repair pathways to gain genomic instability. Biochem J 471:1–11PubMedCrossRefPubMedCentralGoogle Scholar
  45. Kakarougkas A, Ismail A, Chambers AL, Riballo E, Herbert AD, Kunzel J, Lobrich M, Jeggo PA, Downs JA (2014) Requirement for PBAF in transcriptional repression and repair at DNA breaks in actively transcribed regions of chromatin. Mol Cell 55:723–732PubMedPubMedCentralCrossRefGoogle Scholar
  46. Kamsler A, Daily D, Hochman A, Stern N, Shiloh Y, Rotman G, Barzilai A (2001) Increased oxidative stress in ataxia telangiectasia evidenced by alterations in redox state of brains from Atm-deficient mice. Cancer Res 61:1849–1854PubMedPubMedCentralGoogle Scholar
  47. Kanu N, Behrens A (2007) ATMIN defines an NBS1-independent pathway of ATM signalling. EMBO J 26:2933–2941PubMedPubMedCentralCrossRefGoogle Scholar
  48. Kastan MB, Zhan Q, el-Deiry WS, Carrier F, Jacks T, Walsh WV, Plunkett BS, Vogelstein B, Fornace AJ Jr (1992) A mammalian cell cycle checkpoint pathway utilizing p53 and GADD45 is defective in ataxia-telangiectasia. Cell 71:587–597PubMedPubMedCentralCrossRefGoogle Scholar
  49. Katyal S, Lee Y, Nitiss KC, Downing SM, Li Y, Shimada M, Zhao J, Russell HR, Petrini JH, Nitiss JL et al (2014) Aberrant topoisomerase-1 DNA lesions are pathogenic in neurodegenerative genome instability syndromes. Nat Neurosci 17:813–821PubMedPubMedCentralCrossRefGoogle Scholar
  50. Kennedy RD, Chen CC, Stuckert P, Archila EM, De la Vega MA, Moreau LA, Shimamura A, D’Andrea AD (2007) Fanconi anemia pathway-deficient tumor cells are hypersensitive to inhibition of ataxia telangiectasia mutated. J Clin Invest 117:1440–1449PubMedPubMedCentralCrossRefGoogle Scholar
  51. Khoronenkova SV, Dianov GL (2015) ATM prevents DSB formation by coordinating SSB repair and cell cycle progression. Proc Natl Acad Sci U S A 112:3997–4002PubMedPubMedCentralCrossRefGoogle Scholar
  52. Kozlov SV, Graham ME, Peng C, Chen P, Robinson PJ, Lavin MF (2006) Involvement of novel autophosphorylation sites in ATM activation. EMBO J 25:3504–3514PubMedPubMedCentralCrossRefGoogle Scholar
  53. Krueger SA, Wilson GD, Piasentin E, Joiner MC, Marples B (2010) The effects of G2-phase enrichment and checkpoint abrogation on low-dose hyper-radiosensitivity. Int J Radiat Oncol Biol Phys 77:1509–1517PubMedCrossRefPubMedCentralGoogle Scholar
  54. Kruger A, Ralser M (2011) ATM is a redox sensor linking genome stability and carbon metabolism. Sci Signal 4:pe17.  https://doi.org/10.1126/scisignal.2001959 CrossRefPubMedPubMedCentralGoogle Scholar
  55. Kruhlak MJ, Celeste A, Nussenzweig A (2006) Spatio-temporal dynamics of chromatin containing DNA breaks. Cell Cycle 5:1910–1912PubMedCrossRefPubMedCentralGoogle Scholar
  56. Kruhlak M, Crouch EE, Orlov M, Montano C, Gorski SA, Nussenzweig A, Misteli T, Phair RD, Casellas R (2007) The ATM repair pathway inhibits RNA polymerase I transcription in response to chromosome breaks. Nature 447:730–734PubMedCrossRefPubMedCentralGoogle Scholar
  57. Lam QL, Lo CK, Zheng BJ, Ko KH, Osmond DG, Wu GE, Rottapel R, Lu L (2007) Impaired V(D)J recombination and increased apoptosis among B cell precursors in the bone marrow of c-Abl-deficient mice. Int Immunol 19:267–276PubMedCrossRefPubMedCentralGoogle Scholar
  58. Lavin MF, Khanna KK, Beamish H, Teale B, Hobson K, Watters D (1994) Defect in radiation signal transduction in ataxia-telangiectasia. Int J Radiat Biol 66:S151–S156PubMedCrossRefPubMedCentralGoogle Scholar
  59. Lee JH, Paull TT (2005) ATM activation by DNA double-strand breaks through the Mre11-Rad50-Nbs1 complex. Science 308:551–554PubMedPubMedCentralCrossRefGoogle Scholar
  60. Lee JH, Goodarzi AA, Jeggo PA, Paull TT (2010) 53BP1 promotes ATM activity through direct interactions with the MRN complex. EMBO J 29:574–585PubMedCrossRefPubMedCentralGoogle Scholar
  61. Li S, Ting NS, Zheng L, Chen PL, Ziv Y, Shiloh Y, Lee EY, Lee WH (2000) Functional link of BRCA1 and ataxia telangiectasia gene product in DNA damage response. Nature 406:210–215PubMedPubMedCentralCrossRefGoogle Scholar
  62. Lieber MR (2010) The mechanism of double-strand DNA break repair by the nonhomologous DNA end-joining pathway. Annu Rev Biochem 79:181–211PubMedPubMedCentralCrossRefGoogle Scholar
  63. Lin PH, Kuo WH, Huang AC, Lu YS, Lin CH, Kuo SH, Wang MY, Liu CY, Cheng FT, Yeh MH et al (2016) Multiple gene sequencing for risk assessment in patients with early-onset or familial breast cancer. Oncotarget.  https://doi.org/10.18632/oncotarget.7027
  64. Lobrich M, Shibata A, Beucher A, Fisher A, Ensminger M, Goodarzi AA, Barton O, Jeggo PA (2010) Gamma H2AX foci analysis for monitoring DNA double-strand break repair: strengths, limitations and optimization. Cell Cycle 9:662–669PubMedCrossRefPubMedCentralGoogle Scholar
  65. Lovejoy CA, Cortez D (2009) Common mechanisms of PIKK regulation. DNA Repair 8:1004–1008PubMedPubMedCentralCrossRefGoogle Scholar
  66. Lukas C, Melander F, Stucki M, Falck J, Bekker-Jensen S, Goldberg M, Lerenthal Y, Jackson SP, Bartek J, Lukas J (2004) Mdc1 couples DNA double-strand break recognition by Nbs1 with its H2AX-dependent chromatin retention. EMBO J 23:2674–2683PubMedPubMedCentralCrossRefGoogle Scholar
  67. Mailand N, Falck J, Lukas C, Syljuasen RG, Welcker M, Bartek J, Lukas J (2000) Rapid destruction of human Cdc25A in response to DNA damage. Science 288:1425–1429PubMedPubMedCentralCrossRefGoogle Scholar
  68. Mailand N, Bekker-Jensen S, Faustrup H, Melander F, Bartek J, Lukas C, Lukas J (2007) RNF8 ubiquitylates histones at DNA double-strand breaks and promotes assembly of repair proteins. Cell 131:887–900PubMedCrossRefGoogle Scholar
  69. Mallette FA, Mattiroli F, Cui G, Young LC, Hendzel MJ, Mer G, Sixma TK, Richard S (2012) RNF8- and RNF168-dependent degradation of KDM4A/JMJD2A triggers 53BP1 recruitment to DNA damage sites. EMBO J 31:1865–1878PubMedPubMedCentralCrossRefGoogle Scholar
  70. Matt S, Hofmann TG (2016) The DNA damage-induced cell death response: a roadmap to kill cancer cells. Cell Mol Life Sci 73(15):2829–2850PubMedCrossRefPubMedCentralGoogle Scholar
  71. McKinnon PJ (2012) ATM and the molecular pathogenesis of ataxia telangiectasia. Annu Rev Pathol 7:303–321PubMedCrossRefPubMedCentralGoogle Scholar
  72. Nadeu F, Delgado J, Royo C, Baumann T, Stankovic T, Pinyol M, Jares P, Navarro A, Martin-Garcia D, Bea S et al (2016) Clinical impact of clonal and subclonal TP53, SF3B1, BIRC3, NOTCH1 and ATM mutations in chronic lymphocytic leukemia. Blood 127(17):2122–2130PubMedPubMedCentralCrossRefGoogle Scholar
  73. Noon AT, Shibata A, Rief N, Lobrich M, Stewart GS, Jeggo PA, Goodarzi AA (2010) 53BP1-dependent robust localized KAP-1 phosphorylation is essential for heterochromatic DNA double-strand break repair. Nat Cell Biol 12:177–184PubMedCrossRefPubMedCentralGoogle Scholar
  74. Okuno Y, Nakamura-Ishizu A, Otsu K, Suda T, Kubota Y (2012) Pathological neoangiogenesis depends on oxidative stress regulation by ATM. Nat Med 18:1208–1216PubMedCrossRefPubMedCentralGoogle Scholar
  75. Painter RB (1981) Radioresistant DNA synthesis: an intrinsic feature of ataxia telangiectasia. Mutat Res 84:183–190PubMedCrossRefPubMedCentralGoogle Scholar
  76. Perry J, Kleckner N (2003) The ATRs, ATMs, and TORs are giant HEAT repeat proteins. Cell 112:151–155PubMedCrossRefGoogle Scholar
  77. Petermann E, Helleday T (2010) Pathways of mammalian replication fork restart. Nat Rev Mol Cell Biol 11:683–687PubMedCrossRefPubMedCentralGoogle Scholar
  78. Savitsky K, Bar-Shira A, Gilad S, Rotman G, Ziv Y, Vanagaite L, Tagle DA, Smith S, Uziel T, Sfez S et al (1995) A single ataxia telangiectasia gene with a product similar to PI-3 kinase. Science 268:1749–1753PubMedPubMedCentralCrossRefGoogle Scholar
  79. Schalch DS, McFarlin DE, Barlow MH (1970) An unusual form of diabetes mellitus in ataxia telangiectasia. N Engl J Med 282:1396–1402PubMedCrossRefPubMedCentralGoogle Scholar
  80. Seeber A, Hauer M, Gasser SM (2013) Nucleosome remodelers in double-strand break repair. Curr Opin Genet Dev 23:174–184PubMedCrossRefPubMedCentralGoogle Scholar
  81. Shanbhag NM, Rafalska-Metcalf IU, Balane-Bolivar C, Janicki SM, Greenberg RA (2010) ATM-dependent chromatin changes silence transcription in cis to DNA double-strand breaks. Cell 141:970–981PubMedPubMedCentralCrossRefGoogle Scholar
  82. Shibata A, Conrad S, Birraux J, Geuting V, Barton O, Ismail A, Kakarougkas A, Meek K, Taucher-Scholz G, Lobrich M et al (2011) Factors determining DNA double-strand break repair pathway choice in G2 phase. EMBO J 30:1079–1092PubMedPubMedCentralCrossRefGoogle Scholar
  83. Shibata A, Moiani D, Arvai AS, Perry J, Harding SM, Genois MM, Maity R, van Rossum-Fikkert S, Kertokalio A, Romoli F et al (2014) DNA double-strand break repair pathway choice is directed by distinct MRE11 nuclease activities. Mol Cell 53:7–18PubMedCrossRefPubMedCentralGoogle Scholar
  84. Shigeta T, Takagi M, Delia D, Chessa L, Iwata S, Kanke Y, Asada M, Eguchi M, Mizutani S (1999) Defective control of apoptosis and mitotic spindle checkpoint in heterozygous carriers of ATM mutations. Cancer Res 59:2602–2607PubMedPubMedCentralGoogle Scholar
  85. Shiotani B, Zou L (2009) Single-stranded DNA orchestrates an ATM-to-ATR switch at DNA breaks. Mol Cell 33:547–558PubMedPubMedCentralCrossRefGoogle Scholar
  86. Stewart GS, Maser RS, Stankovic T, Bressan DA, Kaplan MI, Jaspers NG, Raams A, Byrd PJ, Petrini JH, Taylor AM (1999) The DNA double-strand break repair gene hMRE11 is mutated in individuals with an ataxia-telangiectasia-like disorder. Cell 99:577–587PubMedCrossRefPubMedCentralGoogle Scholar
  87. Stucki M, Clapperton JA, Mohammad D, Yaffe MB, Smerdon SJ, Jackson SP (2005) MDC1 directly binds phosphorylated histone H2AX to regulate cellular responses to DNA double-strand breaks. Cell 123:1213–1226PubMedCrossRefPubMedCentralGoogle Scholar
  88. Stumm M, Neubauer S, Keindorff S, Wegner RD, Wieacker P, Sauer R (2001) High frequency of spontaneous translocations revealed by FISH in cells from patients with the cancer-prone syndromes ataxia telangiectasia and Nijmegen breakage syndrome. Cytogenet Cell Genet 92:186–191PubMedCrossRefPubMedCentralGoogle Scholar
  89. Sultana R, Abdel-Fatah T, Abbotts R, Hawkes C, Albarakati N, Seedhouse C, Ball G, Chan S, Rakha EA, Ellis IO et al (2013) Targeting XRCC1 deficiency in breast cancer for personalized therapy. Cancer Res 73:1621–1634PubMedPubMedCentralCrossRefGoogle Scholar
  90. Sun Y, Xu Y, Roy K, Price BD (2007) DNA damage-induced acetylation of lysine 3016 of ATM activates ATM kinase activity. Mol Cell Biol 27:8502–8509PubMedPubMedCentralCrossRefGoogle Scholar
  91. Sun Y, Jiang X, Price BD (2010) Tip60: connecting chromatin to DNA damage signaling. Cell Cycle 9:930–936PubMedPubMedCentralCrossRefGoogle Scholar
  92. Takagi M, Delia D, Chessa L, Iwata S, Shigeta T, Kanke Y, Goi K, Asada M, Eguchi M, Kodama C et al (1998) Defective control of apoptosis, radiosensitivity, and spindle checkpoint in ataxia telangiectasia. Cancer Res 58:4923–4929PubMedPubMedCentralGoogle Scholar
  93. Takao N, Li Y, Yamamoto K (2000) Protective roles for ATM in cellular response to oxidative stress. FEBS Lett 472:133–136PubMedCrossRefPubMedCentralGoogle Scholar
  94. Tavtigian SV, Oefner PJ, Babikyan D, Hartmann A, Healey S, Le Calvez-Kelm F, Lesueur F, Byrnes GB, Chuang SC, Forey N et al (2009) Rare, evolutionarily unlikely missense substitutions in ATM confer increased risk of breast cancer. Am J Hum Genet 85:427–446PubMedPubMedCentralCrossRefGoogle Scholar
  95. Tresini M, Warmerdam DO, Kolovos P, Snijder L, Vrouwe MG, Demmers JA, van IJcken WF, Grosveld FG, Medema RH, Hoeijmakers JH et al (2015) The core spliceosome as target and effector of non-canonical ATM signalling. Nature 523:53–58PubMedPubMedCentralCrossRefGoogle Scholar
  96. Ui A, Nagaura Y, Yasui A (2015) Transcriptional elongation factor ENL phosphorylated by ATM recruits polycomb and switches off transcription for DSB repair. Mol Cell 58:468–482PubMedCrossRefPubMedCentralGoogle Scholar
  97. Uziel T, Lerenthal Y, Moyal L, Andegeko Y, Mittelman L, Shiloh Y (2003) Requirement of the MRN complex for ATM activation by DNA damage. EMBO J 22:5612–5621PubMedPubMedCentralCrossRefGoogle Scholar
  98. Wahl GM, Linke SP, Paulson TG, Huang LC (1997) Maintaining genetic stability through TP53 mediated checkpoint control. Cancer Surv 29:183–219PubMedPubMedCentralGoogle Scholar
  99. Watanabe S, Watanabe K, Akimov V, Bartkova J, Blagoev B, Lukas J, Bartek J (2013) JMJD1C demethylates MDC1 to regulate the RNF8 and BRCA1-mediated chromatin response to DNA breaks. Nat Struct Mol Biol 20:1425–1433PubMedCrossRefPubMedCentralGoogle Scholar
  100. Watters D, Kedar P, Spring K, Bjorkman J, Chen P, Gatei M, Birrell G, Garrone B, Srinivasa P, Crane DI et al (1999) Localization of a portion of extranuclear ATM to peroxisomes. J Biol Chem 274:34277–34282PubMedCrossRefPubMedCentralGoogle Scholar
  101. Xu B, Kim ST, Lim DS, Kastan MB (2002) Two molecularly distinct G(2)/M checkpoints are induced by ionizing irradiation. Mol Cell Biol 22:1049–1059PubMedPubMedCentralCrossRefGoogle Scholar
  102. Xu Y, Ayrapetov MK, Xu C, Gursoy-Yuzugullu O, Hu Y, Price BD (2012) Histone H2A.Z controls a critical chromatin remodeling step required for DNA double-strand break repair. Mol Cell 48:723–733PubMedPubMedCentralCrossRefGoogle Scholar
  103. Yang DQ, Kastan MB (2000) Participation of ATM in insulin signalling through phosphorylation of eIF-4E-binding protein 1. Nat Cell Biol 2:893–898PubMedCrossRefPubMedCentralGoogle Scholar
  104. Yang C, Tang X, Guo X, Niikura Y, Kitagawa K, Cui K, Wong ST, Fu L, Xu B (2011) Aurora-B mediated ATM serine 1403 phosphorylation is required for mitotic ATM activation and the spindle checkpoint. Mol Cell 44:597–608PubMedPubMedCentralCrossRefGoogle Scholar
  105. You Z, Chahwan C, Bailis J, Hunter T, Russell P (2005) ATM activation and its recruitment to damaged DNA require binding to the C terminus of Nbs1. Mol Cell Biol 25:5363–5379PubMedPubMedCentralCrossRefGoogle Scholar
  106. Zhang T, Penicud K, Bruhn C, Loizou JI, Kanu N, Wang ZQ, Behrens A (2012) Competition between NBS1 and ATMIN controls ATM signaling pathway choice. Cell Rep 2:1498–1504PubMedCrossRefPubMedCentralGoogle Scholar
  107. Ziv Y, Bielopolski D, Galanty Y, Lukas C, Taya Y, Schultz DC, Lukas J, Bekker-Jensen S, Bartek J, Shiloh Y (2006) Chromatin relaxation in response to DNA double-strand breaks is modulated by a novel ATM- and KAP-1 dependent pathway. Nat Cell Biol 8:870–876PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Eduction and Research Support Centre, Graduate School of MedicineGunma UniversityMaebashiJapan
  2. 2.Genome Damage and Stability Centre, Life SciencesUniversity of SussexBrightonUK

Personalised recommendations