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Mechanisms of non-canonical activation of ataxia telangiectasia mutated

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Abstract

ATM is a master regulator of the cellular response to DNA damage. The classical mechanism of ATM activation involves its monomerization in response to DNA double-strand breaks, resulting in ATM-dependent phosphorylation of more than a thousand substrates required for cell cycle progression, DNA repair, and apoptosis. Here, new experimental evidence for non-canonical mechanisms of ATM activation in response to stimuli distinct from DNA double-strand breaks is discussed. It includes cytoskeletal changes, chromatin modifications, RNA–DNA hybrids, and DNA single-strand breaks. Noncanonical ATM activation may be important for the pathology of the multisystemic disease Ataxia Telangiectasia.

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Abbreviations

А-Т:

Ataxia Telangiectasia

АТМ:

Ataxia Telangiectasia mutated

ATR:

АТМ- and Rad3-related kinase

DNA-PKcs:

DNA-dependent protein kinase catalytic subunit

DSB:

DNA double-strand break

MRN:

Mre11-Rad50-Nbs1 complex

R-loop:

RNA–DNA hybrid

SSB:

DNA single-strand break

Top1:

DNA topoisomerase I

Top1cc:

Top1–DNA intermediate

References

  1. Lavin, M. F., Scott, S., Gueven, N., Kozlov, S., Peng, C., and Chen, P. (2004) Functional consequences of sequence alterations in the ATM gene, DNA Rep. (Amst.), 3, 1197–1205.

    Article  CAS  Google Scholar 

  2. Falck, J., Coates, J., and Jackson, S. P. (2005) Conserved modes of recruitment of ATM, ATR and DNA-PKcs to sites of DNA damage, Nature, 434, 605–611.

    Article  CAS  PubMed  Google Scholar 

  3. Bakkenist, C. J., and Kastan, M. B. (2003) DNA damage activates ATM through intermolecular autophosphorylation and dimer dissociation, Nature, 421, 499–506.

    Article  CAS  PubMed  Google Scholar 

  4. Sun, Y., Jiang, X., Chen, S., Fernandes, N., and Price, B. D. (2005) A role for the Tip60 histone acetyltransferase in the acetylation and activation of ATM, Proc. Natl. Acad. Sci. USA, 102, 13182–13187.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Sun, Y., Xu, Y., Roy, K., and Price, B. D. (2007) DNA damage-induced acetylation of lysine 3016 of ATM activates ATM kinase activity, Mol. Cell. Biol., 27, 8502–8509.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Kozlov, S., Gueven, N., Keating, K., Ramsay, J., and Lavin, M. F. (2003) ATP activates ataxia-telangiectasia mutated (ATM) in vitro. Importance of autophosphorylation, J. Biol. Chem., 278, 9309–9317.

    Article  CAS  PubMed  Google Scholar 

  7. Kozlov, S. V., Graham, M. E., Peng, C., Chen, P., Robinson, P. J., and Lavin, M. F. (2006) Involvement of novel autophosphorylation sites in ATM activation, EMBO J., 25, 3504–3514.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Kozlov, S. V., Graham, M. E., Jakob, B., Tobias, F., Kijas, A. W., Tanuji, M., Chen, P., Robinson, P. J., TaucherScholz, G., Suzuki, K., So, S., Chen, D., and Lavin, M. F. (2011) Autophosphorylation and ATM activation: additional sites add to the complexity, J. Biol. Chem., 286, 9107–9119.

    Article  CAS  PubMed  Google Scholar 

  9. Pellegrini, M., Celeste, A., Difilippantonio, S., Guo, R., Wang, W., Feigenbaum, L., and Nussenzweig, A. (2006) Autophosphorylation at serine 1987 is dispensable for murine ATM activation in vivo, Nature, 443, 222–225.

    Article  CAS  PubMed  Google Scholar 

  10. Daniel, J. A., Pellegrini, M., Lee, J. H., Paull, T. T., Feigenbaum, L., and Nussenzweig, A. (2008) Multiple autophosphorylation sites are dispensable for murine ATM activation in vivo, J. Cell Biol., 183, 777–783.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Uziel, T., Lerenthal, Y., Moyal, L., Andegeko, Y., Mittelman, L., and Shiloh, Y. (2003) Requirement of the MRN complex for ATM activation by DNA damage, EMBO J., 22, 5612–5621.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Carson, C. T., Schwartz, R. A., Stracker, T. H., Lilley, C. E., Lee, D. V., and Weitzman, M. D. (2003) The Mre11 complex is required for ATM activation and the G2/M checkpoint, EMBO J., 22, 6610–6620.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Sun, Y., Jiang, X., Xu, Y., Ayrapetov, M. K., Moreau, L. A., Whetstine, J. R., and Price, B. D. (2009) Histone H3 methylation links DNA damage detection to activation of the tumour suppressor Tip60, Nat. Cell Biol., 11, 1376–1382.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Deshpande, R. A., Williams, G. J., Limbo, O., Williams, R. S., Kuhnlein, J., Lee, J. H., Classen, S., Guenther, G., Russell, P., Tainer, J. A., and Paull, T. T. (2014) ATP-driven Rad50 conformations regulate DNA tethering, end resection, and ATM checkpoint signaling, EMBO J., 33, 482–500.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Bhatti, S., Kozlov, S., Farooqi, A. A., Naqi, A., Lavin, M., and Khanna, K. K. (2011) ATM protein kinase: the linchpin of cellular defenses to stress, Cell. Mol. Life Sci., 68, 2977–3006.

    Article  CAS  PubMed  Google Scholar 

  16. Shiloh, Y., and Ziv, Y. (2013) The ATM protein kinase: regulating the cellular response to genotoxic stress, and more, Nat. Rev. Mol. Cell Biol., 14, 197–210.

    Article  CAS  Google Scholar 

  17. Paull, T. T. (2015) Mechanisms of ATM activation, Annu. Rev. Biochem., 84, 711–738.

    Article  CAS  PubMed  Google Scholar 

  18. Guo, Z., Kozlov, S., Lavin, M. F., Person, M. D., and Paull, T. T. (2010) ATM activation by oxidative stress, Science, 330, 517–521.

    Article  CAS  PubMed  Google Scholar 

  19. Yang, D. Q., and Kastan, M. B. (2000) Participation of ATM in insulin signalling through phosphorylation of eIF-4E-binding protein 1, Nat. Cell Biol., 2, 893–898.

    Article  CAS  PubMed  Google Scholar 

  20. Valentin-Vega, Y. A., Maclean, K. H., Tait-Mulder, J., Milasta, S., Steeves, M., Dorsey, F. C., Cleveland, J. L., Green, D. R., and Kastan, M. B. (2012) Mitochondrial dysfunction in ataxia-telangiectasia, Blood, 119, 1490–1500.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Zhang, J., Tripathi, D. N., Jing, J., Alexander, A., Kim, J., Powell, R. T., Dere, R., Tait-Mulder, J., Lee, J. H., Paull, T. T., Pandita, R. K., Charaka, V. K., Pandita, T. K., Kastan, M. B., and Walker, C. L. (2015) ATM functions at the peroxisome to induce pexophagy in response to ROS, Nat. Cell Biol., 17, 1259–1269.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Kozlov, S. V., Waardenberg, A. J., Engholm-Keller, K., Arthur, J. W., Graham, M. E., and Lavin, M. F. (2015) ROS-activated ATM-dependent phosphorylation of cytoplasmic substrates identified by large scale phosphoproteomics screen, Mol. Cell. Proteomics, 15, 1032–1047.

    Article  PubMed  Google Scholar 

  23. McKinnon, P. J. (2012) ATM and the molecular pathogenesis of ataxia telangiectasia, Annu. Rev. Pathol., 7, 303–321.

    Article  CAS  PubMed  Google Scholar 

  24. Di Domenico, E. G., Romano, E., DEl Porto, P., and Ascenzioni, F. (2014) Multifunctional role of ATM/Tel1 kinase in genome stability: from the DNA damage response to telomere maintenance, Biomed. Res. Int., 2014, 787404.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Shiloh, Y. (2014) ATM: expanding roles as a chief guardian of genome stability, Exp. Cell Res., 329, 154–161.

    Article  CAS  PubMed  Google Scholar 

  26. Lavin, M. F., Kozlov, S., Gatei, M., and Kijas, A. W. (2015) ATM-dependent phosphorylation of all three members of the MRN complex: from sensor to adaptor, Biomolecules, 5, 2877–2902.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Syllaba, L., and Henner, K. (1926) Contribution a le tude de l’inde pendance de l’athe tose double idiopathique et conge nitale. Atteinte familiale, syndrome dystrophique, signe du re sau vasculaire conjonctival, inte grite psychique, Rev. Neurol. (Paris), 1, 541–560.

    Google Scholar 

  28. Louis-Bar, D. (1941) Sur un syndrome progressif cormprenant des telangiectasies capillaires cutanees et conjonctivales symetriques, a disposition naevoide et des troubles cerebelleux, Confin. Neurol., 4, 32–42.

    Article  Google Scholar 

  29. Boder, E., and Sedgwick, R. P. (1958) Ataxia-telangiectasia; a familial syndrome of progressive cerebellar ataxia, oculocutaneous telangiectasia and frequent pulmonary infection, Pediatrics, 21, 526–554.

    CAS  PubMed  Google Scholar 

  30. Su, Y., and Swift, M. (2000) Mortality rates among carriers of ataxia-telangiectasia mutant alleles, Ann. Intern. Med., 133, 770–778.

    Article  CAS  PubMed  Google Scholar 

  31. Swift, M., Morrell, D., Cromartie, E., Chamberlin, A. R., Skolnick, M. H., and Bishop, D. T. (1986) The incidence and gene frequency of ataxia-telangiectasia in the United States, Am. J. Hum. Genet., 39, 573–583.

    CAS  PubMed  PubMed Central  Google Scholar 

  32. Teive, H. A., Moro, A., Moscovich, M., Arruda, W. O., Munhoz, R. P., Raskin, S., and Ashizawa, T. (2015) Ataxiatelangiectasia–a historical review and a proposal for a new designation: ATM syndrome, J. Neurol. Sci., 355, 3–6.

    Article  PubMed  PubMed Central  Google Scholar 

  33. Lindahl, T. (1993) Instability and decay of the primary structure of DNA, Nature, 362, 709–715.

    Article  CAS  PubMed  Google Scholar 

  34. Dianov, G., Price, A., and Lindahl, T. (1992) Generation of single-nucleotide repair patches following excision of uracil residues from DNA, Mol. Cell. Biol., 12, 1605–1612.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Kuzminov, A. (2001) Single-strand interruptions in replicating chromosomes cause double-strand breaks, Proc. Natl. Acad. Sci. USA, 98, 8241–8246.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Zhou, W., and Doetsch, P. W. (1993) Effects of abasic sites and DNA single-strand breaks on prokaryotic RNA polymerases, Proc. Natl. Acad. Sci. USA, 90, 6601–6605.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Kathe, S. D., Shen, G. P., and Wallace, S. S. (2004) Singlestranded breaks in DNA but not oxidative DNA base damages block transcriptional elongation by RNA polymerase II in HeLa cell nuclear extracts, J. Biol. Chem., 279, 18511–18520.

    Article  CAS  PubMed  Google Scholar 

  38. Date, H., Onodera, O., Tanaka, H., Iwabuchi, K., Uekawa, K., Igarashi, S., Koike, R., Hiroi, T., Yuasa, T., Awaya, Y., Sakai, T., Takahashi, T., Nagatomo, H., Sekijima, Y., Kawachi, I., Takiyama, Y., Nishizawa, M., Fukuhara, N., Saito, K., Sugano, S., and Tsuji, S. (2001) Early-onset ataxia with ocular motor apraxia and hypoalbuminemia is caused by mutations in a new HIT superfamily gene, Nat. Genet., 29, 184–188.

    Article  CAS  PubMed  Google Scholar 

  39. Moreira, M. C., Barbot, C., Tachi, N., Kozuka, N., Uchida, E., Gibson, T., Mendonca, P., Costa, M., Barros, J., Yanagisawa, T., Watanabe, M., Ikeda, Y., Aoki, M., Nagata, T., Coutinho, P., Sequeiros, J., and Koenig, M. (2001) The gene mutated in ataxia-ocular apraxia 1 encodes the new HIT/Zn-finger protein aprataxin, Nat. Genet., 29, 189–193.

    Article  CAS  PubMed  Google Scholar 

  40. Takashima, H., Boerkoel, C. F., John, J., Saifi, G. M., Salih, M. A., Armstrong, D., Mao, Y., Quiocho, F. A., Roa, B. B., Nakagawa, M., Stockton, D. W., and Lupski, J. R. (2002) Mutation of TDP1, encoding a topoisomerase Idependent DNA damage repair enzyme, in spinocerebellar ataxia with axonal neuropathy, Nat. Genet., 32, 267–272.

    Article  CAS  PubMed  Google Scholar 

  41. Shen, J., Gilmore, E. C., Marshall, C. A., Haddadin, M., Reynolds, J. J., Eyaid, W., Bodell, A., Barry, B., Gleason, D., Allen, K., Ganesh, V. S., Chang, B. S., Grix, A., Hill, R. S., Topcu, M., Caldecott, K. W., Barkovich, A. J., and Walsh, C. A. (2010) Mutations in PNKP cause microcephaly, seizures and defects in DNA repair, Nat. Genet., 42, 245–249.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Markkanen, E., Fischer, R., Ledentcova, M., Kessler, B. M., and Dianov, G. L. (2015) Cells deficient in base-excision repair reveal cancer hallmarks originating from adjustments to genetic instability, Nucleic Acids Res., 43, 3667–3679.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Khoronenkova, S. V., and Dianov, G. L. (2015) ATM prevents DSB formation by coordinating SSB repair and cell cycle progression, Proc. Natl. Acad. Sci. USA, 112, 3997–4002.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Khoronenkova, S. V., Dianova, I. I., Ternette, N., Kessler, B. M., Parsons, J. L., and Dianov, G. L. (2012) ATMdependent downregulation of USP7/HAUSP by PPM1G activates p53 response to DNA damage, Mol. Cell, 45, 801–813.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Khoronenkova, S. V., and Dianov, G. L. (2013) USP7Sdependent inactivation of Mule regulates DNA damage signalling and repair, Nucleic Acids Res., 41, 1750–1756.

    Article  CAS  PubMed  Google Scholar 

  46. Hoar, D. I., and Sargent, P. (1976) Chemical mutagen hypersensitivity in ataxia telangiectasia, Nature, 261, 590–592.

    Article  CAS  PubMed  Google Scholar 

  47. Yi, M., Rosin, M. P., and Anderson, C. K. (1990) Response of fibroblast cultures from ataxia-telangiectasia patients to oxidative stress, Cancer Lett., 54, 43–50.

    Article  CAS  PubMed  Google Scholar 

  48. Roots, R., Kraft, G., and Gosschalk, E. (1985) The formation of radiation-induced DNA breaks: the ratio of doublestrand breaks to single-strand breaks, Int. J. Radiat. Oncol. Biol. Phys., 11, 259–265.

    Article  CAS  PubMed  Google Scholar 

  49. Champoux, J. J., and Dulbecco, R. (1972) An activity from mammalian cells that untwists superhelical DNA–a possible swivel for DNA replication (polyoma-ethidium bromide-mouse-embryo cells-dye binding assay), Proc. Natl. Acad. Sci. USA, 69, 143–146.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Hsiang, Y. H., Hertzberg, R., Hecht, S., and Liu, L. F. (1985) Camptothecin induces protein-linked DNA breaks via mammalian DNA topoisomerase I, J. Biol. Chem., 260, 14873–14878.

    CAS  PubMed  Google Scholar 

  51. Lin, C. P., Ban, Y., Lyu, Y. L., Desai, S. D., and Liu, L. F. (2008) A ubiquitin-proteasome pathway for the repair of topoisomerase I-DNA covalent complexes, J. Biol. Chem., 283, 21074–21083.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Katyal, S., Lee, Y., Nitiss, K. C., Downing, S. M., Li, Y., Shimada, M., Zhao, J., Russell, H. R., Petrini, J. H., Nitiss, J. L., and McKinnon, P. J. (2014) Aberrant topoisomerase-1 DNA lesions are pathogenic in neurodegenerative genome instability syndromes, Nat. Neurosci., 17, 813–821.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Huertas, P., and Aguilera, A. (2003) Cotranscriptionally formed DNA:RNA hybrids mediate transcription elongation impairment and transcription-associated recombination, Mol. Cell, 12, 711–721.

    Article  CAS  PubMed  Google Scholar 

  54. Tuduri, S., Crabbe, L., Conti, C., Tourriere, H., HoltgreveGrez, H., Jauch, A., Pantesco, V., De Vos, J., Thomas, A., Theillet, C., Pommier, Y., Tazi, J., Coquelle, A., and Pasero, P. (2009) Topoisomerase I suppresses genomic instability by preventing interference between replication and transcription, Nat. Cell Biol., 11, 1315–1324.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Sordet, O., Redon, C. E., Guirouilh-Barbat, J., Smith, S., Solier, S., Douarre, C., Conti, C., Nakamura, A. J., Das, B. B., Nicolas, E., Kohn, K. W., Bonner, W. M., and Pommier, Y. (2009) Ataxia telangiectasia mutated activation by transcription- and topoisomerase I-induced DNA double-strand breaks, EMBO Rep., 10, 887–893.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Cristini, A., Park, J. H., Capranico, G., Legube, G., Favre, G., and Sordet, O. (2015) DNA-PK triggers histone ubiquitination and signaling in response to DNA double-strand breaks produced during the repair of transcription-blocking topoisomerase I lesions, Nucleic Acids Res., 44, 1161–1178.

    Article  PubMed  PubMed Central  Google Scholar 

  57. Sordet, O., Nakamura, A. J., Redon, C. E., and Pommier, Y. (2010) DNA double-strand breaks and ATM activation by transcription-blocking DNA lesions, Cell Cycle, 9, 274–278.

    Article  CAS  PubMed  Google Scholar 

  58. Sollier, J., Stork, C. T., Garcia-Rubio, M. L., Paulsen, R. D., Aguilera, A., and Cimprich, K. A. (2014) Transcription-coupled nucleotide excision repair factors promote R-loop-induced genome instability, Mol. Cell, 56, 777–785.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Tresini, M., Warmerdam, D. O., Kolovos, P., Snijder, L., Vrouwe, M. G., Demmers, J. A., Van Ijcken, W. F., Grosveld, F. G., Medema, R. H., Hoeijmakers, J. H., Mullenders, L. H., Vermeulen, W., and Marteijn, J. A. (2015) The core spliceosome as target and effector of noncanonical ATM signalling, Nature, 523, 53–58.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Price, B. D., and D’Andrea, A. D. (2013) Chromatin remodeling at DNA double-strand breaks, Cell, 152, 1344–1354.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Kaidi, A., and Jackson, S. P. (2013) KAT5 tyrosine phosphorylation couples chromatin sensing to ATM signalling, Nature, 498, 70–74.

    Article  CAS  PubMed  Google Scholar 

  62. Kanu, N., and Behrens, A. (2007) ATMIN defines an NBS1-independent pathway of ATM signalling, EMBO J., 26, 2933–2941.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Bakkenist, C. J., and Kastan, M. B. (2015) Chromatin perturbations during the DNA damage response in higher eukaryotes, DNA Rep. (Amst.), 36, 8–12.

    Article  CAS  Google Scholar 

  64. Kumar, A., Mazzanti, M., Mistrik, M., Kosar, M., Beznoussenko, G. V., Mironov, A. A., Garre, M., Parazzoli, D., Shivashankar, G. V., Scita, G., Bartek, J., and Foiani, M. (2014) ATR mediates a checkpoint at the nuclear envelope in response to mechanical stress, Cell, 158, 633–646.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Goodarzi, A. A., and Jeggo, P. A. (2013) The repair and signaling responses to DNA double-strand breaks, Adv. Genet., 82, 1–45.

    CAS  PubMed  Google Scholar 

  66. Taccioli, G. E., Gottlieb, T. M., Blunt, T., Priestley, A., Demengeot, J., Mizuta, R., Lehmann, A. R., Alt, F. W., Jackson, S. P., and Jeggo, P. A. (1994) Ku80: product of the XRCC5 gene and its role in DNA repair and V(D)J recombination, Science, 265, 1442–1445.

    Article  CAS  PubMed  Google Scholar 

  67. Hartlerode, A. J., Morgan, M. J., Wu, Y., Buis, J., and Ferguson, D. O. (2015) Recruitment and activation of the ATM kinase in the absence of DNA-damage sensors, Nat. Struct. Mol. Biol., 22, 736–743.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Epstein, W. L., Fudenberg, H. H., Reed, W. B., Boder, E., and Sedgwick, R. P. (1966) Immunologic studies in ataxiatelangiectasia. I. Delayed hypersensitivity and serum immune globulin levels in probands and first-degree relatives, Int. Arch. Allergy Appl. Immunol., 30, 15–29.

    Article  CAS  PubMed  Google Scholar 

  69. Boder, E., and Sedgwick, R. P. (1970) Ataxia-telangiectasia (clinical and immunological aspects), Psychiatr. Neurol. Med. Psychol. Beih., 13–14, 8–16.

    PubMed  Google Scholar 

  70. Aguilar, M. J., Kamoshita, S., Landing, B. H., Boder, E., and Sedgwick, R. P. (1968) Pathological observations in ataxia-telangiectasia. A report of five cases, J. Neuropathol. Exp. Neurol., 27, 659–676.

    Article  CAS  PubMed  Google Scholar 

  71. Paula-Barbosa, M. M., Ruela, C., Tavares, M. A., Pontes, C., Saraiva, A., and Cruz, C. (1983) Cerebellar cortex ultrastructure in ataxia-telangiectasia, Ann. Neurol., 13, 297–302.

    Article  CAS  PubMed  Google Scholar 

  72. Vinters, H. V., Gatti, R. A., and Rakic, P. (1985) Sequence of cellular events in cerebellar ontogeny relevant to expression of neuronal abnormalities in ataxia-telangiectasia, Kroc Found. Ser., 19, 233–255.

    CAS  PubMed  Google Scholar 

  73. Barlow, C., Hirotsune, S., Paylor, R., Liyanage, M., Eckhaus, M., Collins, F., Shiloh, Y., Crawley, J. N., Ried, T., Tagle, D., and Wynshaw-Boris, A. (1996) ATM-deficient mice: a paradigm of ataxia telangiectasia, Cell, 86, 159–171.

    Article  CAS  PubMed  Google Scholar 

  74. Barlow, C., Ribaut-Barassin, C., Zwingman, T. A., Pope, A. J., Brown, K. D., Owens, J. W., Larson, D., Harrington, E. A., Haeberle, A. M., Mariani, J., Eckhaus, M., Herrup, K., Bailly, Y., and Wynshaw-Boris, A. (2000) ATM is a cytoplasmic protein in mouse brain required to prevent lysosomal accumulation, Proc. Natl. Acad. Sci. USA, 97, 871–876.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Borghesani, P. R., Alt, F. W., Bottaro, A., Davidson, L., Aksoy, S., Rathbun, G. A., Roberts, T. M., Swat, W., Segal, R. A., and Gu, Y. (2000) Abnormal development of Purkinje cells and lymphocytes in ATM mutant mice, Proc. Natl. Acad. Sci. USA, 97, 3336–3341.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Chen, P., Peng, C., Luff, J., Spring, K., Watters, D., Bottle, S., Furuya, S., and Lavin, M. F. (2003) Oxidative stress is responsible for deficient survival and dendritogenesis in purkinje neurons from ataxia-telangiectasia mutated mutant mice, J. Neurosci., 23, 11453–11460.

    CAS  PubMed  Google Scholar 

  77. Reliene, R., and Schiestl, R. H. (2007) Antioxidants suppress lymphoma and increase longevity in ATM-deficient mice, J. Nutr., 137, 229S–232S.

    CAS  PubMed  Google Scholar 

  78. Rybczynska, M., Pawlak, A. L., Sikorska, E., and Ignatowicz, R. (1996) Ataxia telangiectasia heterozygotes and patients display increased fluidity and decrease in contents of sulfhydryl groups in red blood cell membranes, Biochim. Biophys. Acta, 1302, 231–235.

    Article  PubMed  Google Scholar 

  79. Reichenbach, J., Schubert, R., Schindler, D., Muller, K., Bohles, H., and Zielen, S. (2002) Elevated oxidative stress in patients with ataxia telangiectasia, Antioxid. Redox Signal., 4, 465–469.

    Article  CAS  PubMed  Google Scholar 

  80. Yeo, A. J., Becherel, O. J., Luff, J. E., Cullen, J. K., Wongsurawat, T., Jenjaroenpun, P., Kuznetsov, V. A., McKinnon, P. J., and Lavin, M. F. (2014) R-loops in proliferating cells but not in the brain: implications for AOA2 and other autosomal recessive ataxias, PLoS One, 9, e90219.

    Article  PubMed  PubMed Central  Google Scholar 

  81. Orii, K. E., Lee, Y., Kondo, N., and McKinnon, P. J. (2006) Selective utilization of nonhomologous end-joining and homologous recombination DNA repair pathways during nervous system development, Proc. Natl. Acad. Sci. USA, 103, 10017–10022.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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  1. Department of Biochemistry, University of Cambridge, Cambridge, CB2 1GA, UK

    S. V. Khoronenkova

  2. Department of Chemistry, Lomonosov Moscow State University, 119991, Moscow, Russia

    S. V. Khoronenkova

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Original Russian Text © S. V. Khoronenkova, 2016, published in Uspekhi Biologicheskoi Khimii, 2016, Vol. 56, pp. 197–210.

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Khoronenkova, S.V. Mechanisms of non-canonical activation of ataxia telangiectasia mutated. Biochemistry Moscow 81, 1669–1675 (2016). https://doi.org/10.1134/S0006297916130058

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