ATM protein kinase: The linchpin of cellular defenses to stress

Cellular and Molecular Life Sciences

Volumn 68, Issue 18, 2011, Pages 2977-3006

  Bhatti, Shahzad ^a   Kozlov, Sergei ^b   Farooqi, Ammad Ahmad ^a   Naqi, Ali ^a   Lavin, Martin ^b   Khanna, Kum Kum ^b  

^a UNIVERSITY OF LAHORE   (Pakistan)

^b QIMR BERGHOFER MEDICAL RESEARCH INSTITUTE   (Australia)

Author keywords

ATM kinase; Carcinogenesis; DNA damage response; Signaling

Indexed keywords

AMINO TERMINAL TELOPEPTIDE; ATM PROTEIN; ATR PROTEIN; DNA DEPENDENT PROTEIN KINASE; INSULIN; MRE11 PROTEIN; PHOSPHATIDYLINOSITOL 3 KINASE; PHOSPHATIDYLINOSITOL 3 KINASE LIKE KINASE; RAD50 PROTEIN; RAPAMYCIN; UNCLASSIFIED DRUG; WORTMANNIN;

ATAXIA TELANGIECTASIA; AUTOPHOSPHORYLATION; CARCINOGENESIS; CELL STRESS; CELLULAR IMMUNITY; CHROMATIN STRUCTURE; CYTOPLASM; DNA DAMAGE; ENZYME ACTIVATION; ENZYME ACTIVITY; ENZYME REGULATION; HISTONE MODIFICATION; HUMAN; NONHUMAN; OXIDATIVE STRESS; PHENOTYPE; PROTEIN DNA INTERACTION; PROTEIN EXPRESSION; PROTEIN FUNCTION; REVIEW; SIGNAL TRANSDUCTION;

ATAXIA TELANGIECTASIA; CELL CYCLE PROTEINS; CHROMATIN ASSEMBLY AND DISASSEMBLY; DNA DAMAGE; DNA REPAIR ENZYMES; DNA-BINDING PROTEINS; ENZYME ACTIVATION; HUMANS; MODELS, MOLECULAR; MULTIPROTEIN COMPLEXES; NUCLEAR PROTEINS; OXIDATIVE STRESS; PROTEIN-SERINE-THREONINE KINASES; SIGNAL TRANSDUCTION; TUMOR SUPPRESSOR PROTEINS;

EID: 80052273503     PISSN: 1420682X     EISSN: 14209071     Source Type: Journal    
DOI: 10.1007/s00018-011-0683-9     Document Type: Review

References (274)

1. Shiloh Y (1997) Ataxia-telangiectasia and the Nijmegen breakage syndrome: related disorders but genes apart. Annu Rev Genet 31:635-662. doi:10.1146/annurev.genet.31.1.635 (Pubitemid 28023722)
2. Lavin MF (2008) Ataxia-telangiectasia: from a rare disorder to a paradigm for cell signalling and cancer. Nat Rev Mol Cell Biol 9(10):759-769. doi:10.1038/nrm2514
3. Savitsky K, Bar-Shira A, Gilad S, Rotman G, Ziv Y, Vanagaite L, Tagle DA, Smith S, Uziel T, Sfez S, Ashkenazi M, Pecker I, Frydman M, Harnik R, Patanjali SR, Simmons A, Clines GA, Sartiel A, Gatti RA, Chessa L, Sanal O, Lavin MF, Jaspers NG, Taylor AM, Arlett CF, Miki T, Weissman SM, Lovett M, Collins FS, Shiloh Y (1995) A single ataxia telangiectasia gene with a product similar to PI-3 kinase. Science 268(5218):1749-1753
4. Lee JH, Paull TT (2007) Activation and regulation of ATM kinase activity in response to DNA double-strand breaks. Oncogene 26(56):7741-7748. doi:10.1038/sj.onc.1210872 (Pubitemid 350242454)
5. Lempiainen H, Halazonetis TD (2009) Emerging common themes in regulation of PIKKs and PI3Ks. EMBO J 28(20): 3067-3073. doi:10.1038/emboj.2009.281
6. Venkitaraman AR (2010) Modifying chromatin architecture during the response to DNA breakage. Crit Rev Biochem Mol Biol 45(1):2-13. doi:10.3109/10409230903325446
7. Durocher D, Jackson SP (2001) DNA-PK, ATM and ATR as sensors of DNA damage: variations on a theme? Curr Opin Cell Biol 13(2):225-231. pii:S0955-0674(00)00201-5 (Pubitemid 32209224)
8. Bosotti R, Isacchi A, Sonnhammer EL (2000) FAT: a novel domain in PIK-related kinases. Trends Biochem Sci 25(5):225-227. pii:S0968-0004(00)01563-2 (Pubitemid 30236217)
9. Rivera-Calzada A, Maman JD, Spagnolo L, Pearl LH, Llorca O (2005) Three-dimensional structure and regulation of the DNA-dependent protein kinase catalytic subunit (DNA-PKcs). Structure 13(2):243-255. doi:10.1016/j.str.2004. 12.006 (Pubitemid 40247700)
10. Llorca O, Rivera-Calzada A, Grantham J, Willison KR (2003) Electron microscopy and 3D reconstructions reveal that human ATM kinase uses an arm-like domain to clamp around double-stranded DNA. Oncogene 22(25):3867-3874. doi:10.1038/sj. onc.1206649 (Pubitemid 36819660)
11. Sibanda BL, Chirgadze DY, Blundell TL (2010) Crystal structure of DNA-PKcs reveals a large open-ring cradle comprised of HEAT repeats. Nature 463(7277):118-121. doi:10.1038/ nature08648
12. Takahashi T, Hara K, Inoue H, Kawa Y, Tokunaga C, Hidayat S, Yoshino K, Kuroda Y, Yonezawa K (2000) Carboxyl-terminal region conserved among phosphoinositide-kinase-related kina-ses is indispensable for mTOR function in vivo and in vitro. Genes Cells 5(9):765-775 gtc365[pii]
13. Mordes DA, Cortez D (2008) Activation of ATR and related PIKKs. Cell Cycle 7(18):2809-2812 6689[pii]
14. Jiang X, Sun Y, Chen S, Roy K, Price BD (2006) The FATC domains of PIKK proteins are functionally equivalent and participate in the Tip60-dependent activation of DNA-PKcs and ATM. J Biol Chem 281(23):15741-15746. doi:10.1074/jbc. M513172200 (Pubitemid 44537031)
15. 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(24):8502-8509. doi:10.1128/MCB. 01382-07
16. Kozlov SV, Graham ME, Jakob B, Tobias F, Kijas AW, Tanuji M, Chen P, Robinson PJ, Taucher-Scholz G, Suzuki K, So S, Chen D, Lavin MF (2010) Autophosphorylation and ATM activation: additional sites add to the complexity. J Biol Chem. doi:10.1074/jbc.M110.204065
17. Bensimon A, Schmidt A, Ziv Y, Elkon R, Wang SY, Chen DJ, Aebersold R, Shiloh Y (2010) ATM-dependent and-independent dynamics of the nuclear phosphoproteome after DNA damage. Sci Signal 3(151):rs3. doi:10.1126/scisignal. 2001034
18. Pirola L, Zvelebil MJ, Bulgarelli-Leva G, Van Obberghen E, Waterfield MD, Wymann MP (2001) Activation loop sequences confer substrate specificity to phosphoinositide 3-kinase alpha (PI3Kalpha). Functions of lipid kinase-deficient PI3Kalpha in signaling. J Biol Chem 276(24):21544-21554. doi:10.1074/jbc. M011330200
19. Douglas P, Cui X, Block WD, Yu Y, Gupta S, Ding Q, Ye R, Morrice N, Lees-Miller SP, Meek K (2007) The DNA-depen-dent protein kinase catalytic subunit is phosphorylated in vivo on threonine 3950, a highly conserved amino acid in the protein kinase domain. Mol Cell Biol 27(5):1581-1591. doi:10.1128/ MCB.01962-06
20. Falck J, Coates J, Jackson SP (2005) Conserved modes of recruitment of ATM, ATR and DNA-PKcs to sites of DNA damage. Nature 434(7033):605-611. doi:10.1038/nature03442 (Pubitemid 40488547)
21. 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(13):5363-5379. doi:10.1128/MCB.25.13.5363-5379.2005 (Pubitemid 40853574)
22. Mordes DA, Glick GG, Zhao R, Cortez D (2008) TopBP1 activates ATR through ATRIP and a PIKK regulatory domain. Genes Dev 22(11):1478-1489. doi:10.1101/gad.1666208 (Pubitemid 351793082)
23. Lovejoy CA, Cortez D (2009) Common mechanisms of PIKK regulation. DNA Repair (Amst) 8(9):1004-1008. doi:10.1016/j. dnarep.2009.04.006
24. Kanu N, Behrens A (2007) ATMIN defines an NBS1-indepen-dent pathway of ATM signalling. EMBO J 26(12):2933-2941. doi:10.1038/sj.emboj.7601733 (Pubitemid 46975782)
25. Heierhorst J (2008) Mdt1/ASCIZ: a new DNA damage response protein family. Cell Cycle 7(17):2654-2660. pii:6593
26. Guo JY, Yamada A, Kajino T, Wu JQ, Tang W, Freel CD, Feng J, Chau BN, Wang MZ, Margolis SS, Yoo HY, Wang XF, Dunphy WG, Irusta PM, Hardwick JM, Kornbluth S (2008) Aven-dependent activation of ATM following DNA damage. Curr Biol 18(13):933-942. doi:10.1016/j.cub.2008.05.045
27. Richard DJ, Bolderson E, Cubeddu L, Wadsworth RI, Savage K, Sharma GG, Nicolette ML, Tsvetanov S, McIlwraith MJ, Pandita RK, Takeda S, Hay RT, Gautier J, West SC, Paull TT, Pandita TK, White MF, Khanna KK (2008) Single-stranded DNA-binding protein hSSB1 is critical for genomic stability. Nature 453(7195):677-681. doi:10.1038/nature06883 (Pubitemid 351769294)
28. Goodarzi AA, Jonnalagadda JC, Douglas P, Young D, Ye R, Moorhead GB, Lees-Miller SP, Khanna KK (2004) Autophos-phorylation of ataxia-telangiectasia mutated is regulated by protein phosphatase 2A. EMBO J 23(22):4451-4461. doi: 10.1038/sj.emboj.7600455 (Pubitemid 39601970)
29. Li H, Balajee AS, Su T, Cen B, Hei TK, Weinstein IB (2008) The HINT1 tumor suppressor regulates both gamma-H2AX and ATM in response to DNA damage. J Cell Biol 183(2):253-265. doi:10.1083/jcb.200711150
30. Takai H, Wang RC, Takai KK, Yang H, de Lange T (2007) Tel2 regulates the stability of PI3K-related protein kinases. Cell 131(7):1248-1259. doi:10.1016/j.cell.2007.10.052 (Pubitemid 350297416)
31. Anderson CM, Korkin D, Smith DL, Makovets S, Seidel JJ, Sali A, Blackburn EH (2008) Tel2 mediates activation and localization of ATM/Tel1 kinase to a double-strand break. Genes Dev 22(7):854-859. doi:10.1101/gad.1646208 (Pubitemid 351482837)
32. Paulsen RD, Soni DV, Wollman R, Hahn AT, Yee MC, Guan A, Hesley JA, Miller SC, Cromwell EF, Solow-Cordero DE, Meyer T, Cimprich KA (2009) A genome-wide siRNA screen reveals diverse cellular processes and pathways that mediate genome stability. Mol Cell 35(2):228-239. doi:10.1016/j.molcel. 2009.06.021
33. Kolas NK, Chapman JR, Nakada S, Ylanko J, Chahwan R, Sweeney FD, Panier S, Mendez M, Wildenhain J, Thomson TM, Pelletier L, Jackson SP, Durocher D (2007) Orchestration of the DNA-damage response by the RNF8 ubiquitin ligase. Science 318(5856):1637-1640. doi:10.1126/science.1150034 (Pubitemid 350233664)
34. Takai H, Xie Y, de Lange T, Pavletich NP (2010) Tel2 structure and function in the Hsp90-dependent maturation of mTOR and ATR complexes. Genes Dev 24(18):2019-2030. doi:10.1101/ gad.1956410
35. Horejsi Z, Takai H, Adelman CA, Collis SJ, Flynn H, Maslen S, Skehel JM, de Lange T, Boulton SJ (2010) CK2 phospho-dependent binding of R2TP complex to TEL2 is essential for mTOR and SMG1 stability. Mol Cell 39(6):839-850. doi: 10.1016/j.molcel.2010.08.037
36. Hurov KE, Cotta-Ramusino C, Elledge SJ (2010) A genetic screen identifies the Triple T complex required for DNA damage signaling and ATM and ATR stability. Genes Dev 24(17): 1939-1950. doi:10.1101/gad.1934210
37. Kaizuka T, Hara T, Oshiro N, Kikkawa U, Yonezawa K, Takehana K, Iemura S, Natsume T, Mizushima N (2010) Tti1 and Tel2 are critical factors in mammalian target of rapamycin complex assembly. J Biol Chem 285(26):20109-20116. doi: 10.1074/jbc.M110.121699
38. Zhang N, Kaur R, Akhter S, Legerski RJ (2009) Cdc5L interacts with ATR and is required for the S-phase cell-cycle checkpoint. EMBO Rep 10(9):1029-1035. doi:10.1038/embor.2009.122
39. Li DQ, Ohshiro K, Khan MN, Kumar R (2010) Requirement of MTA1 in ATR-mediated DNA damage checkpoint function. J Biol Chem 285(26):19802-19812. doi:10.1074/jbc.M109. 085258
40. Schmidt DR, Schreiber SL (1999) Molecular association between ATR and two components of the nucleosome remodeling and deacetylating complex, HDAC2 and CHD4. Biochemistry 38(44):14711-14717. pii:bi991614n
41. Guo Z, Kozlov S, Lavin MF, Person MD, Paull TT (2010) ATM activation by oxidative stress. Science 330(6003):517-521. doi: 10.1126/science.1192912
42. Barzilai A, Rotman G, Shiloh Y (2002) ATM deficiency and oxidative stress: a new dimension of defective response to DNA damage. DNA Repair (Amst) 1(1):3-25. pii:S1568786401 000076 (Pubitemid 34475690)
43. Barzilai A, Biton S, Shiloh Y (2008) The role of the DNA damage response in neuronal development, organization and maintenance. DNA Repair (Amst) 7(7):1010-1027. doi: 10.1016/j.dnarep.2008.03.005
44. Dames SA, Mulet JM, Rathgeb-Szabo K, Hall MN, Grzesiek S (2005) The solution structure of the FATC domain of the protein kinase target of rapamycin suggests a role for redox-dependent structural and cellular stability. J Biol Chem 280(21): 20558-20564. doi:10.1074/jbc.M501116200 (Pubitemid 40776757)
45. Perry J, Kleckner N (2003) The ATRs, ATMs, and TORs are giant HEAT repeat proteins. Cell 112(2):151-155. pii:S009286 7403000333 (Pubitemid 36144105)
46. Brewerton SC, Dore AS, Drake AC, Leuther KK, Blundell TL (2004) Structural analysis of DNA-PKcs: modelling of the repeat units and insights into the detailed molecular architecture. J Struct Biol 145(3):295-306. doi:10.1016/j.jsb.2003.11.024 (Pubitemid 38198300)
47. Ali A, Zhang J, Bao S, Liu I, Otterness D, Dean NM, Abraham RT, Wang XF (2004) Requirement of protein phosphatase 5 in DNA-damage-induced ATM activation. Genes Dev 18(3):249-254. doi:10.1101/gad.1176004 (Pubitemid 38199250)
48. Chen BP, Uematsu N, Kobayashi J, Lerenthal Y, Krempler A, Yajima H, Lobrich M, Shiloh Y, Chen DJ (2007) Ataxia tel-angiectasia mutated (ATM) is essential for DNA-PKcs phosphorylations at the Thr-2609 cluster upon DNA double-strand break. J Biol Chem 282(9):6582-6587. doi:10.1074/jbc. M611605200 (Pubitemid 47100815)
49. Yajima H, Lee KJ, Chen BP (2006) ATR-dependent phos-phorylation of DNA-dependent protein kinase catalytic subunit in response to UV-induced replication stress. Mol Cell Biol 26(20):7520-7528. doi:10.1128/MCB.00048-06 (Pubitemid 44547702)
50. Khanna KK, Keating KE, Kozlov S, Scott S, Gatei M, Hobson K, Taya Y, Gabrielli B, Chan D, Lees-Miller SP, Lavin MF (1998) ATM associates with and phosphorylates p53: mapping the region of interaction. Nat Genet 20(4):398-400. doi: 10.1038/3882 (Pubitemid 28541643)
51. Fernandes N, Sun Y, Chen S, Paul P, Shaw RJ, Cantley LC, Price BD (2005) DNA damage-induced association of ATM with its target proteins requires a protein interaction domain in the N terminus of ATM. J Biol Chem 280(15):15158-15164. doi:10.1074/jbc.M412065200 (Pubitemid 40562870)
52. Young DB, Jonnalagadda J, Gatei M, Jans DA, Meyn S, Khanna KK (2005) Identification of domains of ataxia-telangiectasia mutated required for nuclear localization and chromatin association. J Biol Chem 280(30):27587-27594. doi:10.1074/jbc.M411 689200 (Pubitemid 41076870)
53. Seidel JJ, Anderson CM, Blackburn EH (2008) A novel Tel1/ ATM N-terminal motif, TAN, is essential for telomere length maintenance and a DNA damage response. Mol Cell Biol 28(18):5736-5746. doi:10.1128/MCB.00326-08
54. Kozlov SV, Graham ME, Peng C, Chen P, Robinson PJ, Lavin MF (2006) Involvement of novel autophosphorylation sites in ATM activation. EMBO J 25(15):3504-3514. doi:10.1038/sj. emboj.7601231 (Pubitemid 44264861)
55. Davis AJ, So S, Chen DJ (2010) Dynamics of the PI3K-like protein kinase members ATM and DNA-PKcs at DNA double-strand breaks. Cell Cycle 9 (13). pii:12148
56. Beamish H, Kedar P, Kaneko H, Chen P, Fukao T, Peng C, Beresten S, Gueven N, Purdie D, Lees-Miller S, Ellis N, Kondo N, Lavin MF (2002) Functional link between BLM defective in Bloom's syndrome and the ataxia-telangiectasia-mutated protein, ATM. J Biol Chem 277(34):30515-30523. doi:10.1074/jbc. M203801200 (Pubitemid 34970744)
57. Soutoglou E, Misteli T (2008) Activation of the cellular DNA damage response in the absence of DNA lesions. Science 320(5882):1507-1510. doi:10.1126/science.1159051 (Pubitemid 351929432)
58. Chen X, Zhao R, Glick GG, Cortez D (2007) Function of the ATR N-terminal domain revealed by an ATM/ATR chimera. Exp Cell Res 313(8):1667-1674. doi:10.1016/j.yexcr.2007.02.015 (Pubitemid 46589442)
59. Haince JF, Kozlov S, Dawson VL, Dawson TM, Hendzel MJ, Lavin MF, Poirier GG (2007) Ataxia telangiectasia mutated (ATM) signaling network is modulated by a novel poly(ADP-ribose)-dependent pathway in the early response to DNA-dam-aging agents. J Biol Chem 282(22):16441-16453. doi:10.1074/ jbc.M608406200 (Pubitemid 47100334)
60. Goodarzi AA, Lees-Miller SP (2004) Biochemical characterization of the ataxia-telangiectasia mutated (ATM) protein from human cells. DNA Repair (Amst) 3(7):753-767. doi:10.1016/ j.dnarep.2004.03.041 (Pubitemid 38716104)
61. Stilmann M, Hinz M, Arslan SC, Zimmer A, Schreiber V, Scheidereit C (2009) A nuclear poly(ADP-ribose)-dependent signalosome confers DNA damage-induced IkappaB kinase activation. Mol Cell 36(3):365-378. doi:10.1016/j.molcel.2009. 09.032
62. Huang TT, Wuerzberger-Davis SM, Wu ZH, Miyamoto S (2003) Sequential modification of NEMO/IKKgamma by SUMO-1 and ubiquitin mediates NF-kappaB activation by genotoxic stress. Cell 115(5):565-576. pii:S009286740300895X (Pubitemid 37506045)
63. Wu ZH, Shi Y, Tibbetts RS, Miyamoto S (2006) Molecular linkage between the kinase ATM and NF-kappaB signaling in response to genotoxic stimuli. Science 311(5764):1141-1146. doi:10.1126/science.1121513
64. Aguilar-Quesada R, Munoz-Gamez JA, Martin-Oliva D, Peralta A, Valenzuela MT, Matinez-Romero R, Quiles-Perez R, Menissier-de Murcia J, de Murcia G, Ruiz de Almodovar M, Oliver FJ (2007) Interaction between ATM and PARP-1 in response to DNA damage and sensitization of ATM deficient cells through PARP inhibition. BMC Mol Biol 8:29. doi: 10.1186/1471-2199-8-29 (Pubitemid 47096976)
65. Carney JP, Maser RS, OlivaresH,Davis EM,LeBeauM,Yates JR 3rd, Hays L, Morgan WF, Petrini JH (1998) The hMre11/hRad50 protein complex and Nijmegen breakage syndrome: linkage of double-strand break repair to the cellular DNA damage response. Cell 93(3):477-486. pii:S0092-8674(00)81175-7 (Pubitemid 28232091)
66. 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(6):577-587. pii:S0092-8674(00)81547-0 (Pubitemid 30004634)
67. Waltes R, Kalb R, Gatei M, Kijas AW, Stumm M, Sobeck A, Wieland B, Varon R, Lerenthal Y, Lavin MF, Schindler D, Dork T (2009) Human RAD50 deficiency in a Nijmegen breakage syndrome-like disorder. Am J Hum Genet 84(5):605-616. doi: 10.1016/j.ajhg.2009.04.010
68. 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(20):5612-5621. doi: 10.1093/emboj/cdg541 (Pubitemid 37279970)
69. Paull TT, Gellert M (1998) The 3' to 5' exonuclease activity of Mre 11 facilitates repair of DNA double-strand breaks. Mol Cell 1(7):969-979. pii:S1097-2765(00)80097-0 (Pubitemid 128379258)
70. Hopfner KP, Karcher A, Shin DS, Craig L, Arthur LM, Carney JP, Tainer JA (2000) Structural biology of Rad50 ATPase: ATP-driven conformational control in DNA double-strand break repair and the ABC-ATPase superfamily. Cell 101(7):789-800. pii:S0092-8674(00)80890-9
71. Bhaskara V,Dupre A,LengsfeldB,Hopkins BB, Chan A,Lee JH, Zhang X, Gautier J, Zakian V, Paull TT (2007) Rad50 adenylate kinase activity regulates DNA tethering by Mre11/Rad50 complexes. Mol Cell 25(5):647-661. doi:10.1016/j. molcel.2007.01. 028 (Pubitemid 46341919)
72. Desai-Mehta A, Cerosaletti KM, Concannon P (2001) Distinct functional domains of nibrin mediate Mre11 binding, focus formation, and nuclear localization. Mol Cell Biol 21(6): 2184-2191. doi:10.1128/MCB.21.6.2184-2191. 2001 (Pubitemid 32479638)
73. de Jager M, van Noort J, van Gent DC, Dekker C, Kanaar R, Wyman C (2001) Human Rad50/Mre11 is a flexible complex that can tether DNA ends. Mol Cell 8(5):1129-1135. pii:S1097-2765(01)00381-1 (Pubitemid 34031814)
74. Paull TT, Lee JH (2005) The Mre11/Rad50/Nbs1 complex and its role as a DNA double-strand break sensor for ATM. Cell Cycle 4(6):737-740. pii:1715 (Pubitemid 41353819)
75. Moncalian G, Lengsfeld B, Bhaskara V, Hopfner KP, Karcher A, Alden E, Tainer JA, Paull TT (2004) The rad50 signature motif: essential to ATP binding and biological function. J Mol Biol 335(4):937-951. doi:S0022283603014219[pii] (Pubitemid 38091602)
76. van der Linden E, Sanchez H, Kinoshita E, Kanaar R, Wyman C (2009) RAD50 and NBS1 form a stable complex functional in DNA binding and tethering. Nucleic Acids Res 37(5):1580-1588. doi:10.1093/nar/gkn1072
77. Hopfner KP, Karcher A, Craig L, Woo TT, Carney JP, Tainer JA (2001) Structural biochemistry and interaction architecture of the DNA double-strand break repair Mre11 nuclease and Rad50-ATPase. Cell 105(4):473-485. pii:S0092-8674(01)00335-X (Pubitemid 32520853)
78. Hopfner KP, Craig L, Moncalian G, Zinkel RA, Usui T, Owen BA, Karcher A, Henderson B, Bodmer JL, McMurray CT, Carney JP, Petrini JH, Tainer JA (2002) The Rad50 zinc-hook is a structure joining Mre11 complexes in DNA recombination and repair. Nature 418(6897):562-566. doi:10.1038/nature00922 (Pubitemid 34851405)
79. Moreno-Herrero F, de Jager M, Dekker NH, Kanaar R, Wyman C, Dekker C (2005) Mesoscale conformational changes in the DNA-repair complex Rad50/Mre11/Nbs1 upon binding DNA. Nature 437(7057):440-443. doi:10.1038/nature03927 (Pubitemid 41613509)
80. Williams RS, Moncalian G, Williams JS, Yamada Y, Limbo O, Shin DS, Groocock LM, Cahill D, Hitomi C, Guenther G, Moiani D, Carney JP, Russell P, Tainer JA (2008) Mre11 dimers coordinate DNA end bridging and nuclease processing in double-strand-break repair. Cell 135(1):97-109. doi:10.1016/j.cell. 2008.08.017
81. Williams RS, Dodson GE, Limbo O, Yamada Y, Williams JS, Guenther G, Classen S, Glover JN, Iwasaki H, Russell P, Tainer JA (2009) Nbs1 flexibly tethers Ctp1 and Mre11-Rad50 to coordinate DNA double-strand break processing and repair. Cell 139(1):87-99. doi:10.1016/j.cell.2009.07.033
82. 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(3):290-294. doi:10.1038/ng845
83. Yazdi PT, Wang Y, Zhao S, Patel N, Lee EY, Qin J (2002) SMC1 is a downstream effector in the ATM/NBS1 branch of the human S-phase checkpoint. Genes Dev 16(5):571-582. doi: 10.1101/gad.970702 (Pubitemid 34212490)
84. Buscemi G, Savio C, Zannini L, Micciche F, Masnada D, Nakanishi M, Tauchi H, Komatsu K, Mizutani S, Khanna K, Chen P, Concannon P, Chessa L, Delia D (2001) Chk2 activation dependence on Nbs1 after DNA damage. Mol Cell Biol 21(15):5214-5222. doi:10.1128/MCB.21.15.5214-5222.2001 (Pubitemid 32656416)
85. Lee JH, Paull TT (2004) Direct activation of the ATM protein kinase by the Mre11/Rad50/Nbs1 complex. Science 304(5667):93-96. doi:10.1126/science. 1091496 (Pubitemid 38451463)
86. Dong Z, Zhong Q, Chen PL (1999) The Nijmegen breakage syndrome protein is essential for Mre11 phosphorylation upon DNA damage. J Biol Chem 274(28):19513-19516
87. Yuan SS, Chang HL, Hou MF, Chan TF, Kao YH, Wu YC, Su JH (2002) Neocarzinostatin induces Mre11 phosphorylation and focus formation through an ATM-and NBS1-dependent mechanism. Toxicology 177(2-3):123-130. pii:S0300483X02002202
88. Costanzo V, Paull T, Gottesman M, Gautier J (2004) Mre11 assembles linear DNA fragments into DNA damage signaling complexes. PLoS Biol 2(5):E110 doi:10.1371/journal.pbio. 0020110
89. Matsuoka S, Ballif BA, Smogorzewska A, McDonald ER 3rd, Hurov KE, Luo J, Bakalarski CE, ZhaoZ,Solimini N,Lerenthal Y, Shiloh Y, Gygi SP, Elledge SJ (2007) ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage. Science 316(5828):1160-1166. doi:10.1126/science. 1140321 (Pubitemid 46877472)
90. Linding R, Jensen LJ, Ostheimer GJ, van Vugt MA, Jorgensen C, Miron IM, Diella F, Colwill K, Taylor L, Elder K, Metalni-kov P, Nguyen V, Pasculescu A, Jin J, Park JG, Samson LD, Woodgett JR, Russell RB, Bork P, Yaffe MB, Pawson T (2007) Systematic discovery of in vivo phosphorylation networks. Cell 129(7):1415-1426. doi:10.1016/j.cell.2007.05.052 (Pubitemid 46962092)
91. Di Virgilio M, Ying CY, Gautier J (2009) PIKK-dependent phosphorylation of Mre11 induces MRN complex inactivation by disassembly from chromatin. DNA Repair (Amst) 8(11): 1311-1320. doi:10.1016/j.dnarep.2009.07.006
92. Yuan Z, Zhang X, Sengupta N, Lane WS, Seto E (2007) SIRT1 regulates the function of the Nijmegen breakage syndrome protein. Mol Cell 27(1):149-162. doi:10.1016/j.molcel.2007. 05.029 (Pubitemid 46991383)
93. Chailleux C, Tyteca S, Papin C, Boudsocq F, Puget N, Couril-leau C, Grigoriev M, Canitrot Y, Trouche D (2010) Physical interaction between the histone acetyl transferase Tip60 and the DNA double-strand breaks sensor MRN complex. Biochem J 426(3):365-371. doi:10.1042/BJ20091329
94. Robert F, Hardy S, Nagy Z, Baldeyron C, Murr R, Dery U, Masson JY, Papadopoulo D, Herceg Z, Tora L (2006) The transcriptional histone acetyltransferase cofactor TRRAP associates with the MRN repair complex and plays a role in DNA double-strand break repair. Mol Cell Biol 26(2):402-412. doi: 10.1128/MCB.26.2.402-412.2006 (Pubitemid 43089755)
95. Murr R, Loizou JI, Yang YG, Cuenin C, Li H, Wang ZQ, Herceg Z (2006) Histone acetylation by Trrap-Tip60 modulates loading of repair proteins and repair of DNA double-strand breaks. Nat Cell Biol 8(1):91-99. doi:10.1038/ncb1343 (Pubitemid 43064802)
96. Sun Y, Jiang X, Xu Y, Ayrapetov MK, Moreau LA, Whetstine JR, Price BD (2009) Histone H3 methylation links DNA damage detection to activation of the tumour suppressor Tip60. Nat Cell Biol 11(11):1376-1382. doi:10.1038/ncb1982
97. Vaquero A, Scher M, Erdjument-Bromage H, Tempst P, Serrano L, Reinberg D (2007) SIRT1 regulates the histone methyl-transferase SUV39H1 during heterochromatin formation. Nature 450(7168):440-444. doi:10.1038/nature06268 (Pubitemid 350126745)
98. Boisvert FM, Dery U, Masson JY, Richard S (2005) Arginine methylation of MRE11 by PRMT1 is required for DNA damage checkpoint control. Genes Dev 19(6):671-676. doi:10.1101/gad. 1279805 (Pubitemid 40395078)
99. Lou Z, Minter-Dykhouse K, Franco S, Gostissa M, Rivera MA, Celeste A, Manis JP, van Deursen J, Nussenzweig A, Paull TT, Alt FW, Chen J (2006) MDC1 maintains genomic stability by participating in the amplification of ATM-dependent DNA damage signals. Mol Cell 21(2):187-200. doi:10.1016/j.molcel. 2005. 11.025 (Pubitemid 43099935)
100. Wu L, Luo K, Lou Z, Chen J (2008) MDC1 regulates intra-S-phase checkpoint by targeting NBS1 to DNA double-strand breaks. Proc Natl Acad Sci U S A 105(32):11200-11205. doi: 10.1073/pnas.0802885105
101. Chapman JR, Jackson SP (2008) Phospho-dependent interactions between NBS1 and MDC1 mediate chromatin retention of the MRN complex at sites of DNA damage. EMBO Rep 9(8):795-801. doi:10.1038/embor.2008.103
102. Spycher C, Miller ES, Townsend K, Pavic L, Morrice NA, Janscak P, Stewart GS, Stucki M (2008) Constitutive phos-phorylation of MDC1 physically links the MRE11-RAD50-NBS1 complex to damaged chromatin. J Cell Biol 181(2): 227-240. doi:10.1083/jcb.200709008 (Pubitemid 351574549)
103. RaiR, Dai H, Multani AS, Li K, Chin K, Gray J, Lahad JP, Liang J, Mills GB, Meric-Bernstam F, Lin SY (2006) BRIT1 regulates early DNA damage response, chromosomal integrity, and cancer. Cancer Cell 10(2):145-157. doi:10.1016/j.ccr.2006.07.002 (Pubitemid 44175904)
104. Peng G, Yim EK, Dai H, Jackson AP, Burgt I, Pan MR, Hu R, Li K, Lin SY (2009) BRIT1/MCPH1 links chromatin remodelling to DNA damage response. Nat Cell Biol 11(7):865-872. doi: 10.1038/ncb1895
105. Kumar A, Fernandez-Capetillo O, Carrera AC (2010) Nuclear phosphoinositide 3-kinase beta controls double-strand break DNA repair. Proc Natl Acad Sci USA 107(16):7491-7496. doi: 10.1073/pnas.0914242107
106. Mimitou EP, Symington LS (2009) DNA end resection: many nucleases make light work. DNA Repair (Amst) 8(9):983-995. doi:10.1016/j.dnarep.2009.04.017
107. Jazayeri A, Falck J, Lukas C, Bartek J, Smith GC, Lukas J, Jackson SP (2006) ATM-and cell cycle-dependent regulation of ATR in response to DNA double-strand breaks. Nat Cell Biol 8(1):37-45. doi:10.1038/ncb1337 (Pubitemid 43064795)
108. Myers JS, Cortez D (2006) Rapid activation of ATR by ionizing radiation requires ATM and Mre11. J Biol Chem 281(14): 9346-9350. doi:10.1074/jbc. M513265200 (Pubitemid 43864651)
109. Zou L, Elledge SJ (2003) Sensing DNA damage through ATRIP recognition of RPA-ssDNA complexes. Science 300(5625): 1542-1548. doi:10.1126/science.1083430 (Pubitemid 36682880)
110. Zou L (2007) Single-and double-stranded DNA: building a trigger of ATR-mediated DNA damage response. Genes Dev 21(8):879-885. doi:10.1101/gad. 1550307 (Pubitemid 46625637)
111. Olson E, Nievera CJ, Liu E, Lee AY, Chen L, Wu X (2007) The Mre11 complex mediates the S-phase checkpoint through an interaction with replication protein A. Mol Cell Biol 27(17): 6053-6067. doi:10.1128/MCB.00532-07 (Pubitemid 47326694)
112. Lee AY, Liu E, Wu X (2007) The Mre11/Rad50/Nbs1 complex plays an important role in the prevention of DNA rereplication in mammalian cells. J Biol Chem 282(44):32243-32255. doi: 10.1074/jbc.M705486200 (Pubitemid 350106413)
113. Zhong H, Bryson A, Eckersdorff M, Ferguson DO (2005) Rad50 depletion impacts upon ATR-dependent DNA damage responses. Hum Mol Genet 14(18):2685-2693. doi:10.1093/hmg/ ddi302 (Pubitemid 41300641)
114. Stiff T, Cerosaletti K, Concannon P, O'Driscoll M, Jeggo PA (2008) Replication independent ATR signalling leads to G2/M arrest requiring Nbs1, 53BP1 and MDC1. Hum Mol Genet 17(20):3247-3253. doi:10.1093/hmg/ddn220
115. Tomimatsu N, Mukherjee B, Burma S (2009) Distinct roles of ATR and DNA-PKcs in triggering DNA damage responses in ATM-deficient cells. EMBO Rep 10(6):629-635. doi:10.1038/ embor.2009.60
116. Shiotani B, Zou L (2009) Single-stranded DNA orchestrates an ATM-to-ATR switch at DNA breaks. Mol Cell 33(5):547-558. doi:10.1016/j.molcel.2009.01.024
117. Takemura H, Rao VA, Sordet O, Furuta T, Miao ZH, Meng L, Zhang H, Pommier Y (2006) Defective Mre11-dependent activation of Chk2 by ataxia telangiectasia mutated in colorectal carcinoma cells in response to replication-dependent DNA double-strand breaks. J Biol Chem 281(41):30814-30823. doi: 10.1074/jbc. M603747200 (Pubitemid 44582136)
118. Roques C, Coulombe Y, Delannoy M, Vignard J, Grossi S, Brodeur I, Rodrigue A, Gautier J, Stasiak AZ, Stasiak A, Con-stantinou A, Masson JY (2009) MRE11-RAD50-NBS1 is a critical regulator of FANCD2 stability and function during DNA double-strand break repair. EMBO J 28(16):2400-2413. doi: 10.1038/emboj.2009.193
119. Zhu XD, Kuster B, Mann M, Petrini JH, de Lange T (2000) Cell-cycle-regulated association of RAD50/MRE11/NBS1 with TRF2 and human telomeres. Nat Genet 25(3):347-352. doi: 10.1038/77139 (Pubitemid 30437327)
120. de Lange T (2005) Shelterin: the protein complex that shapes and safeguards human telomeres. Genes Dev 19(18):2100-2110. doi:10.1101/gad.1346005 (Pubitemid 41330312)
121. Verdun RE, Crabbe L, Haggblom C, Karlseder J (2005) Functional human telomeres are recognized as DNA damage in G2 of the cell cycle. Mol Cell 20(4):551-561. doi:10.1016/j.molcel. 2005.09.024 (Pubitemid 41668640)
122. Deng Y, Guo X, Ferguson DO, Chang S (2009) Multiple roles for MRE11 at uncapped telomeres. Nature 460(7257):914-918. doi:10.1038/nature08196
123. Dimitrova N, de Lange T (2009) Cell cycle-dependent role of MRN at dysfunctional telomeres: ATM signaling-dependent induction of nonhomologous end joining (NHEJ) in G1 and resection-mediated inhibition of NHEJ in G2. Mol Cell Biol 29(20):5552-5563. doi:10.1128/MCB.00476-09
124. Karlseder J, Hoke K, Mirzoeva OK, Bakkenist C, Kastan MB, Petrini JH, de Lange T (2004) The telomeric protein TRF2 binds the ATM kinase and can inhibit the ATM-dependent DNA damage response. PLoS Biol 2(8):E240. doi:10.1371/journal. pbio.0020240
125. Denchi EL, de Lange T (2007) Protection of telomeres through independent control of ATM and ATR by TRF2 and POT1. Nature 448(7157):1068-1071. doi:10.1038/nature06065 (Pubitemid 47345583)
126. Zhong ZH, Jiang WQ, Cesare AJ, Neumann AA, Wadhwa R, Reddel RR (2007) Disruption of telomere maintenance by depletion of the MRE11/RAD50/NBS1 complex in cells that use alternative lengthening of telomeres. J Biol Chem 282(40): 29314-29322. doi:10.1074/jbc.M701413200 (Pubitemid 350043331)
127. Chen G, Lee E (1996) The product of the ATM gene is a 370-kDa nuclear phosphoprotein. J Biol Chem 271(52):33693-33697 (Pubitemid 27010190)
128. Canman CE, Lim DS, Cimprich KA, Taya Y, Tamai K, Sak-aguchi K, Appella E, Kastan MB, Siliciano JD (1998) Activation of the ATM kinase by ionizing radiation and phos-phorylation of p53. Science 281(5383):1677-1679 (Pubitemid 28435584)
129. Banin S, Moyal L, Shieh S, Taya Y, Anderson CW, Chessa L, Smorodinsky NI, Prives C, Reiss Y, Shiloh Y, Ziv Y (1998) Enhanced phosphorylation of p53 by ATM in response to DNA damage. Science 281(5383):1674-1677
130. Keegan KS, Holtzman DA, Plug AW, Christenson ER, Brainerd EE, Flaggs G, Bentley NJ, Taylor EM, Meyn MS, Moss SB, Carr AM, Ashley T, Hoekstra MF (1996) The Atr and Atm protein kinases associate with different sites along meiotically pairing chromosomes. Genes Dev 10(19):2423-2437 (Pubitemid 26341878)
131. Chan DW, Son SC, Block W, Ye R, Khanna KK, Wold MS, Douglas P, Goodarzi AA, Pelley J, Taya Y, Lavin MF, Lees-Miller SP (2000) Purification and characterization of ATM from human placenta. A manganese-dependent, Wortmannin-sensi-tive serine/threonine protein kinase. J Biol Chem 275(11): 7803-7810 (Pubitemid 30159686)
132. Kozlov S, Gueven N, Keating K, Ramsay J, Lavin MF (2003) ATP activates ataxia-telangiectasia mutated (ATM) in vitro. Importance of autophosphorylation. J Biol Chem 278(11): 9309-9317 (Pubitemid 36800415)
133. Bakkenist CJ, Kastan MB (2003) DNA damage activates ATM through intermolecular autophosphorylation and dimer dissociation. Nature 421(6922):499-506. doi:10.1038/nature01368 (Pubitemid 36168436)
134. Sun Y, Jiang X, Chen S, Fernandes N, Price BD (2005) A role for the Tip60 histone acetyltransferase in the acetylation and activation of ATM. Proc Natl Acad Sci USA 102(37):13182-13187. doi:10.1073/pnas.0504211102 (Pubitemid 41324998)
135. 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(6):683-690. doi:10.1038/ ncb1599 (Pubitemid 47214731)
136. So S, Davis AJ, Chen DJ (2009) Autophosphorylation at serine 1981 stabilizes ATM at DNA damage sites. J Cell Biol 187(7):977-990. doi:10.1083/jcb.200906064
137. Bennetzen MV, Larsen DH, Bunkenborg J, Bartek J, Lukas J, Andersen JS (2010) Site-specific phosphorylation dynamics of the nuclear proteome during the DNA damage response. Mol Cell Proteomics 9(6):1314-1323. doi:10.1074/mcp. M900616-MCP200
138. Carson CT, Schwartz RA, Stracker TH, Lilley CE, Lee DV, Weitzman MD (2003) The Mre11 complex is required for ATM activation and the G2/M checkpoint. EMBO J 22(24): 6610-6620. doi:10.1093/emboj/cdg630 (Pubitemid 38009607)
139. Cerosaletti K, Concannon P (2004) Independent roles for nibrin and Mre11-Rad50 in the activation and function of Atm. J Biol Chem 279(37):38813-38819. doi:10.1074/jbc.M404294200 (Pubitemid 39296040)
140. Lee JH, Paull TT (2005) ATM activation by DNA double-strand breaks through the Mre11-Rad50-Nbs1 complex. Science 308(5721):551-554. doi:10.1126/science.1108297 (Pubitemid 40570585)
141. Dupre A, Boyer-Chatenet L, Gautier J (2006) Two-step activation of ATM by DNA and the Mre11-Rad50-Nbs1 complex. Nat Struct Mol Biol 13(5):451-457. doi:10.1038/nsmb1090 (Pubitemid 43881586)
142. You Z, Bailis JM, Johnson SA, Dilworth SM, Hunter T (2007) Rapid activation of ATM on DNA flanking double-strand breaks. Nat Cell Biol 9(11):1311-1318. doi:10.1038/ncb1651 (Pubitemid 350042363)
143. Jazayeri A, Balestrini A, Garner E, Haber JE, Costanzo V (2008) Mre11-Rad50-Nbs1-dependent processing of DNA breaks generates oligonucleotides that stimulate ATM activity. EMBO J 27(14):1953-1962. doi:10.1038/emboj.2008.128
144. Kitagawa R, Bakkenist CJ, McKinnon PJ, Kastan MB (2004) Phosphorylation of SMC1 is a critical downstream event in the ATM-NBS1-BRCA1 pathway. Genes Dev 18(12):1423-1438. doi:10.1101/gad.1200304 (Pubitemid 38780629)
145. Lee JH, Goodarzi AA, Jeggo PA, Paull TT (2010) 53BP1 promotes ATM activity through direct interactions with the MRN complex. EMBO J 29(3):574-585. doi:10.1038/emboj.2009.372
146. Shreeram S, Demidov ON, Hee WK, Yamaguchi H, Onishi N, Kek C, Timofeev ON, Dudgeon C, Fornace AJ, Anderson CW, Minami Y, Appella E, Bulavin DV (2006) Wip1 phosphatase modulates ATM-dependent signaling pathways. Mol Cell 23(5):757-764. doi:10.1016/j.molcel.2006.07.010 (Pubitemid 44308587)
147. Goldstine JV, Nahas S, Gamo K, Gartler SM, Hansen RS, Ro-elfsema JH, Gatti RA, Marahrens Y (2006) Constitutive phosphorylation of ATM in lymphoblastoid cell lines from patients with ICF syndrome without downstream kinase activity. DNA Repair (Amst) 5(4):432-443. doi:10.1016/j.dnarep.2005. 12.002
148. Jiang YL, Rigolet M, Bourc'his D, Nigon F, Bokesoy I, Fryns JP, Hulten M, Jonveaux P, Maraschio P, Megarbane A, Moncla A, Viegas-Pequignot E (2005) DNMT3B mutations and DNA methylation defect define two types of ICF syndrome. Hum Mutat 25(1):56-63. doi:10.1002/humu.20113 (Pubitemid 40075914)
149. Pellegrini M, Celeste A, Difilippantonio S, Guo R, Wang W, Feigenbaum L, Nussenzweig A (2006) Autophosphorylation at serine 1987 is dispensable for murine Atm activation in vivo. Nature 443(7108):222-225. doi:10.1038/nature05112 (Pubitemid 44387611)
150. 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(5):777-783. doi:10.1083/jcb.200805154
151. Lavin MF, Kozlov S (2007) ATM activation and DNA damage response. Cell Cycle 6(8):931-942. pii:4180 (Pubitemid 46658748)
152. Stiff T, Walker SA, Cerosaletti K, Goodarzi AA, Petermann E, Concannon P, O'Driscoll M, Jeggo PA (2006) ATR-dependent phosphorylation and activation of ATM in response to UV treatment or replication fork stalling. EMBO J 25(24):5775-5782. doi:10.1038/sj.emboj.7601446 (Pubitemid 44967761)
153. Yoo HY, Kumagai A, Shevchenko A, Dunphy WG (2009) The Mre11-Rad50-Nbs1 complex mediates activation of TopBP1 by ATM. Mol Biol Cell 20(9):2351-2360. doi:10.1091/mbc.E08-12-1190
154. Suzuki A, Kusakai G, Kishimoto A, Lu J, Ogura T, Lavin MF, Esumi H (2003) Identification of a novel protein kinase mediating Akt survival signaling to the ATM protein. J Biol Chem 278(1):48-53. doi:10.1074/jbc.M206025200 (Pubitemid 36043542)
155. Tian B, Yang Q, Mao Z (2009) Phosphorylation of ATM by Cdk5 mediates DNA damage signalling and regulates neuronal death. Nat Cell Biol 11(2):211-218. doi:10.1038/ncb1829
156. Anne SL, Saudou F, Humbert S (2007) Phosphorylation of huntingtin by cyclin-dependent kinase 5 is induced by DNA damage and regulates wild-type and mutant huntingtin toxicity in neurons. J Neurosci 27(27):7318-7328. doi:10.1523/JNEUR OSCI.1831-07.2007 (Pubitemid 47037570)
157. Wang X, Zeng L, Wang J, Chau JF, Lai KP, Jia D, Poonepalli A, Hande MP, Liu H, He G, He L, Li B (2011) A positive role for c-Abl in Atm and Atr activation in DNA damage response. Cell Death Differ 18(1):5-15. doi:10.1038/cdd.2010.106
158. Shafman T, Khanna KK, Kedar P, Spring K, Kozlov S, Yen T, Hobson K, Gatei M, Zhang N, Watters D, Egerton M, Shiloh Y, Kharbanda S, Kufe D, Lavin MF (1997) Interaction between ATM protein and c-Abl in response to DNA damage. Nature 387(6632):520-523. doi:10.1038/387520a0 (Pubitemid 27235472)
159. Baskaran R, Wood LD, Whitaker LL, Canman CE, Morgan SE, Xu Y, Barlow C, Baltimore D, Wynshaw-Boris A, Kastan MB
160. Wang JY (1997) Ataxia telangiectasia mutant protein activates c-Abl tyrosine kinase in response to ionizing radiation. Nature 387(6632):516-519. doi:10.1038/387516a0 (Pubitemid 27235471)
161. Wang Y, Cortez D, Yazdi P, Neff N, Elledge SJ, Qin J (2000) BASC, a super complex of BRCA1-associated proteins involved in the recognition and repair of aberrant DNA structures. Genes Dev 14(8):927-939 (Pubitemid 30253002)
162. Meetei AR, Sechi S, Wallisch M, Yang D, Young MK, Joenje H, Hoatlin ME, Wang W (2003) A multiprotein nuclear complex connects Fanconi anemia and Bloom syndrome. Mol Cell Biol 23(10):3417-3426 (Pubitemid 36539175)
163. Simbulan-Rosenthal CM, Rosenthal DS, Hilz H, Hickey R, Malkas L, Applegren N, Wu Y, Bers G, Smulson ME (1996) The expression of poly(ADP-ribose) polymerase during differentiation-linked DNA replication reveals that it is a component of the multiprotein DNA replication complex. Biochemistry 35(36):11622-11633. doi:10.1021/bi953010z (Pubitemid 26303679)
164. Frouin I, Montecucco A, Spadari S, Maga G (2003) DNA replication: a complex matter. EMBO Rep 4(7):666-670. doi: 10.1038/sj.embor.embor886 (Pubitemid 36974750)
165. Painter RB, Young BR (1980) Radiosensitivity in ataxia-telan-giectasia: a new explanation. Proc Natl Acad Sci USA 77(12): 7315-7317
166. Houldsworth J, Lavin MF (1980) Effect of ionizing radiation on DNA synthesis in ataxia telangiectasia cells. Nucleic Acids Res 8(16):3709-3720 (Pubitemid 11246365)
167. Smith PJ, Anderson CO, Watson JV (1985) Effects of X-irra-diation and sodium butyrate on cell-cycle traverse on normal and radiosensitive lymphoblastoid cells. Exp Cell Res 160(2):331-342 (Pubitemid 16251287)
168. Pandita TK (2002) ATM function and telomere stability. Oncogene 21(4):611-618. doi:10.1038/sj.onc.1205060 (Pubitemid 34146261)
169. Grattarola M, Spaggiari S, Chessa L, Savio C, Nicolini C, Vergani L (2003) A structural characterization of in situ chromatin on cell lines isolated from patients affected by ataxia telangiectasia. Int J Biol Macromol 33(1-3):23-29. pii:S0141813003000606
170. Aguilar MJ, Kamoshita S, Landing BH, Boder E, Sedgwick RP (1968) Pathological observations in ataxia-telangiectasia. A report of five cases. J Neuropathol Exp Neurol 27(4):659-676
171. Perlman ZE, Mitchison TJ, Mayer TU (2005) High-content screening and profiling of drug activity in an automated cen-trosome-duplication assay. Chembiochem 6(1):145-151. doi: 10.1002/cbic.200400266
172. Gately DP, Hittle JC, Chan GK, Yen TJ (1998) Characterization of ATM expression, localization, and associated DNA-depen-dent protein kinase activity. Mol Biol Cell 9(9):2361-2374 (Pubitemid 28425881)
173. Andegeko Y, Moyal L, Mittelman L, Tsarfaty I, Shiloh Y, Rotman G (2001) Nuclear retention of ATM at sites of DNA double-strand breaks. J Biol Chem 276(41):38224-38230. doi: 10.1074/jbc.M102986200
174. Kleinschmidt JA, Steinbeisser H (1991) DNA-dependent phos-phorylation of histone H2A.X during nucleosome assembly in Xenopus laevis oocytes: involvement of protein phosphorylation in nucleosome spacing. EMBO J 10(10):3043-3050 (Pubitemid 21905323)
175. Banerjee S, Smallwood A, Hulten M (1995) ATP-dependent reorganization of human sperm nuclear chromatin. J Cell Sci 108(Pt 2):755-765
176. Pilch DR, Sedelnikova OA, Redon C, Celeste A, Nussenzweig A, Bonner WM (2003) Characteristics of gamma-H2AX foci at DNA double-strand breaks sites. Biochem Cell Biol 81(3): 123-129. doi:10.1139/o03-042 (Pubitemid 37076234)
177. Cowell IG, Sunter NJ, Singh PB, Austin CA, Durkacz BW, Tilby MJ (2007) gammaH2AX foci form preferentially in euchromatin after ionising-radiation. PLoS One 2(10):e1057. doi:10.1371/journal.pone.0001057 (Pubitemid 351552222)
178. Kim JA, Kruhlak M, Dotiwala F, Nussenzweig A, Haber JE (2007) Heterochromatin is refractory to gamma-H2AX modification in yeast and mammals. J Cell Biol 178(2):209-218. doi: 10.1083/jcb.200612031 (Pubitemid 47076458)
179. Costes SV, Ponomarev A, Chen JL, Nguyen D, Cucinotta FA, Barcellos-Hoff MH (2007) Image-based modeling reveals dynamic redistribution of DNA damage into nuclear sub-domains. PLoS Comput Biol 3(8):e155. doi:10.1371/journal.pcbi. 0030155 (Pubitemid 47358057)
180. Hauptner A, Krucken R, Greubel C, Hable V, Dollinger G, Drexler GA, Deutsch M, Lowe R, Friedl AA, Dietzel S, Strickfaden H, Cremer T (2006) DNA-repair protein distribution along the tracks of energetic ions. Radiat Prot Dosimetry 122(1-4):147-149. doi:10.1093/rpd/ncl420 (Pubitemid 47090440)
181. Tobias F, Durante M, Taucher-Scholz G, Jakob B (2010) Spatio-temporal analysis of DNA repair using charged particle radiation. Mutat Res 704(1-3):54-60. doi:10.1016/j.mrrev.2009.11.004
182. Savic V, Yin B, Maas NL, Bredemeyer AL, Carpenter AC, Helmink BA, Yang-Iott KS, Sleckman BP, Bassing CH (2009) Formation of dynamic gamma-H2AX domains along broken DNA strands is distinctly regulated by ATM and MDC1 and dependent upon H2AX densities in chromatin. Mol Cell 34(3):298-310. doi:10.1016/j.molcel.2009.04.012
183. Iacovoni JS, Caron P, Lassadi I, Nicolas E, Massip L, Trouche D, Legube G (2010) High-resolution profiling of gammaH2AX around DNA double-strand breaks in the mammalian genome. EMBO J 29(8):1446-1457. doi:10.1038/emboj.2010.38
184. Xiao A, Li H, Shechter D, Ahn SH, Fabrizio LA, Erdjument-Bromage H, Ishibe-Murakami S, Wang B, Tempst P, Hofmann K, Patel DJ, Elledge SJ, Allis CD (2009) WSTF regulates the H2A.X DNA damage response via a novel tyrosine kinase activity. Nature 457(7225):57-62. doi:10.1038/nature07668
185. Poot RA, Bozhenok L, van den Berg DL, Steffensen S, Ferreira F, Grimaldi M, Gilbert N, Ferreira J, Varga-Weisz PD (2004) The Williams syndrome transcription factor interacts with PCNA to target chromatin remodelling by ISWI to replication foci. Nat Cell Biol 6(12):1236-1244. doi:10.1038/ncb1196 (Pubitemid 39625123)
186. Kinner A, Wu W, Staudt C, Iliakis G (2008) Gamma-H2AX in recognition and signaling of DNA double-strand breaks in the context of chromatin. Nucleic Acids Res 36(17):5678-5694. doi:10.1093/nar/gkn550
187. 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(7):1213-1226. doi:10.1016/j.cell.2005. 09.038 (Pubitemid 41821780)
188. Cohn MA, D'Andrea AD (2008) Chromatin recruitment of DNA repair proteins: lessons from the Fanconi anemia and double-strand break repair pathways. Mol Cell 32(3):306-312. doi: 10.1016/j.molcel.2008.10.009
189. Ikura T, Tashiro S, Kakino A, Shima H, Jacob N, Amunugama R, Yoder K, Izumi S, Kuraoka I, Tanaka K, Kimura H, Ikura M, Nishikubo S, Ito T, Muto A, Miyagawa K, Takeda S, Fishel R, Igarashi K, Kamiya K (2007) DNA damage-dependent acety-lation and ubiquitination of H2AX enhances chromatin dynamics. Mol Cell Biol 27(20):7028-7040. doi:10.1128/MCB. 00579-07 (Pubitemid 47549742)
190. van Attikum H, Gasser SM (2009) Crosstalk between histone modifications during the DNA damage response. Trends Cell Biol 19(5):207-217. doi:10.1016/j.tcb.2009.03.001
191. Rossetto D, Truman AW, Kron SJ, Cote J (2010) Epigenetic modifications in double-strand break DNA damage signaling and repair. Clin Cancer Res 16(18):4543-4552. doi:10.1158/ 1078-0432.CCR-10-0513
192. Lee HS, Park JH, Kim SJ, Kwon SJ, Kwon J (2010) A cooperative activation loop among SWI/SNF, gamma-H2AX and H3 acetylation for DNA double-strand break repair. EMBO J 29(8):1434-1445. doi:10.1038/emboj.2010.27
193. Park JH, Park EJ, Lee HS, Kim SJ, Hur SK, Imbalzano AN, Kwon J (2006) Mammalian SWI/SNF complexes facilitate DNA double-strand break repair by promoting gamma-H2AX induction. EMBO J 25(17):3986-3997. doi:10.1038/sj.emboj. 7601291 (Pubitemid 44338741)
194. Kruhlak MJ, Celeste A, Dellaire G, Fernandez-Capetillo O, Muller WG, McNally JG, Bazett-Jones DP, Nussenzweig A (2006) Changes in chromatin structure and mobility in living cells at sites of DNA double-strand breaks. J Cell Biol 172(6):823-834. doi:10.1083/jcb.200510015
195. Green CM, Almouzni G (2002) When repair meets chromatin. First in series on chromatin dynamics. EMBO Rep 3(1):28-33. doi:10.1093/embo-reports/kvf005 (Pubitemid 34144811)
196. Ayoub N, Jeyasekharan AD, Bernal JA, Venkitaraman AR (2008) HP1-beta mobilization promotes chromatin changes that initiate the DNA damage response. Nature 453(7195):682-686. doi:10.1038/nature06875 (Pubitemid 351769293)
197. Kim YC, Gerlitz G, Furusawa T, Catez F, Nussenzweig A, Oh KS, Kraemer KH, Shiloh Y, Bustin M (2009) Activation of ATM depends on chromatin interactions occurring before induction of DNA damage. Nat Cell Biol 11(1):92-96. doi: 10.1038/ncb1817
198. Ayoub N, Jeyasekharan AD, Venkitaraman AR (2009) Mobilization and recruitment of HP1: a bimodal response to DNA breakage. Cell Cycle 8(18):2945-2950. pii:9486
199. Keller DM, Zeng X, Wang Y, Zhang QH, Kapoor M, Shu H, Goodman R, Lozano G, Zhao Y, Lu H (2001) A DNA damage-induced p53 serine 392 kinase complex contains CK2, hSpt16, and SSRP1. Mol Cell 7(2):283-292. pii:S1097-2765(01)00176- 9 (Pubitemid 32206496)
200. Ghavidel A, Schultz MC (2001) TATA binding protein-associated CK2 transduces DNA damage signals to the RNA polymerase III transcriptional machinery. Cell 106(5):575-584. pii:S0092-8674(01)00473-1 (Pubitemid 32879319)
201. Lim AC, Hou Z, Goh CP, Qi RZ (2004) Protein kinase CK2 is an inhibitor of the neuronal Cdk5 kinase. J Biol Chem 279(45):46668-46673. doi:10.1074/jbc. M404760200 (Pubitemid 39518313)
202. 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(8):870-876. doi:10.1038/ncb1446 (Pubitemid 44151591)
203. Li X, Lee YK, Jeng JC, Yen Y, Schultz DC, Shih HM, Ann DK (2007) Role for KAP1 serine 824 phosphorylation and sumoy-lation/desumoylation switch in regulating KAP1-mediated transcriptional repression. J Biol Chem 282(50):36177-36189. doi:10.1074/jbc.M706912200
204. Li X, Lin HH, Chen H, Xu X, Shih HM, Ann DK (2010) SU-MOylation of the transcriptional co-repressor KAP1 is regulated by the serine and threonine phosphatase PP1. Sci Signal 3(119):ra32. doi:10.1126/scisignal.2000781
205. Schultz DC, Ayyanathan K, Negorev D, Maul GG, Rauscher FJ 3rd (2002) SETDB1: a novel KAP-1-associated histone H3, lysine 9-specific methyltransferase that contributes to HP1-mediated silencing of euchromatic genes by KRAB zinc-finger proteins. Genes Dev 16(8):919-932. doi:10.1101/gad.973302 (Pubitemid 34408542)
206. Lechner MS, Begg GE, Speicher DW, Rauscher FJ 3rd (2000) Molecular determinants for targeting heterochromatin protein 1-mediated gene silencing: direct chromoshadow domain-KAP-1 corepressor interaction is essential. Mol Cell Biol 20(17):6449-6465 (Pubitemid 30650232)
207. Goodarzi AA, Noon AT, Deckbar D, Ziv Y, Shiloh Y, Lobrich M, Jeggo PA (2008) ATM signaling facilitates repair of DNA double-strand breaks associated with heterochromatin. Mol Cell 31(2):167-177. doi:10.1016/j.molcel.2008.05.017 (Pubitemid 352001394)
208. Innes CL, Heinloth AN, Flores KG, Sieber SO, Deming PB, Bushel PR, Kaufmann WK, Paules RS (2006) ATM requirement in gene expression responses to ionizing radiation in human lymphoblasts and fibroblasts. Mol Cancer Res 4(3):197-207. doi:10.1158/1541-7786.MCR-05-0154
209. 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(6):970-981. doi:10.1016/j.cell.2010.04.038
210. 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(7145):730-734. doi:10.1038/nature05842 (Pubitemid 46889725)
211. O'Sullivan RJ, Karlseder J (2010) Telomeres: protecting chromosomes against genome instability. Nat Rev Mol Cell Biol 11(3):171-181. doi:10.1038/nrm2848
212. Sampath SC, Marazzi I, Yap KL, Krutchinsky AN, Mecklenb-rauker I, Viale A, Rudensky E, Zhou MM, Chait BT, Tarakhovsky A (2007) Methylation of a histone mimic within the histone methyltransferase G9a regulates protein complex assembly. Mol Cell 27(4):596-608. doi:10.1016/j.molcel. 2007.06.026 (Pubitemid 47238630)
213. Lehner B, Crombie C, Tischler J, Fortunato A, Fraser AG (2006) Systematic mapping of genetic interactions in Caenorhabditis elegans identifies common modifiers of diverse signaling pathways. Nat Genet 38(8):896-903. doi:10.1038/ng1844 (Pubitemid 44141657)
214. Liu JJ, Chung TK, Li J, Taneja R (2010) Sharp-1 modulates the cellular response to DNA damage. FEBS Lett 584(3):619-624. doi:10.1016/j.febslet.2009.12. 011
215. Watters D, Kedar P, Spring K, Bjorkman J, Chen P, Gatei M, Birrell G, Garrone B, Srinivasa P, Crane DI, Lavin MF (1999) Localization of a portion of extranuclear ATM to peroxisomes. J Biol Chem 274(48):34277-34282 (Pubitemid 129511769)
216. Alexander A, Cai SL, Kim J, Nanez A, Sahin M, MacLean KH, Inoki K, Guan KL, Shen J, Person MD, Kusewitt D, Mills GB, Kastan MB, Walker CL (2010) ATM signals to TSC2 in the cytoplasm to regulate mTORC1 in response to ROS. Proc Natl Acad Sci USA 107(9):4153-4158. doi:10.1073/pnas.091 3860107
217. Li J, Han YR, Plummer MR, Herrup K (2009) Cytoplasmic ATM in neurons modulates synaptic function. Curr Biol 19(24):2091-2096. doi:10.1016/j.cub.2009. 10.039
218. Barlow C, Ribaut-Barassin C, Zwingman TA, Pope AJ, Brown KD, Owens JW, Larson D, Harrington EA, Haeberle AM, Mariani J, Eckhaus M, Herrup K, Bailly Y, Wynshaw-Boris A (2000) ATM is a cytoplasmic protein in mouse brain required to prevent lysosomal accumulation. Proc Natl Acad Sci USA 97(2):871-876 (Pubitemid 30070402)
219. Chen P, Peng C, Luff J, Spring K, Watters D, Bottle S, Furuya S, Lavin MF (2003) Oxidative stress is responsible for deficient survival and dendritogenesis in Purkinje neurons from ataxia-telangiectasia mutated mutant mice. J Neurosci 23(36):11453-11460. pii:23/36/11453 (Pubitemid 37549702)
220. Kim TS, Kawaguchi M, Suzuki M, Jung CG, Asai K, Shibamoto Y, Lavin MF, Khanna KK, Miura Y (2010) The ZFHX3 (ATBF1) transcription factor induces PDGFRB, which activates ATM in the cytoplasm to protect cerebellar neurons from oxi-dative stress. Dis Model Mech 3(11-12):752-762. doi:10.1242/ dmm.004689
221. Biton S, Dar I, Mittelman L, Pereg Y, Barzilai A, Shiloh Y (2006) Nuclear ataxia-telangiectasia mutated (ATM) mediates the cellular response to DNA double-strand breaks in human neuron-like cells. J Biol Chem 281(25):17482-17491. doi: 10.1074/jbc.M601895200
222. Boehrs JK, He J, Halaby MJ, Yang DQ (2007) Constitutive expression and cytoplasmic compartmentalizationofATM protein in differentiated human neuron-like SH-SY5Y cells. J Neurochem 100(2):337-345. doi:10.1111/j.1471-4159. 2006.04254.x (Pubitemid 46010995)
223. EngmannO,CampbellJ,WardM,GieseKP,ThompsonAJ(2010) Comparison of a protein-level and peptide-level labeling strategy for quantitative proteomics of synaptosomes using isobaric tags. J Proteome Res 9(5):2725-2733. doi:10.1021/pr900627e
224. Schrimpf SP, Meskenaite V, Brunner E, Rutishauser D, Walther P, Eng J, Aebersold R, Sonderegger P (2005) Proteomic analysis of synaptosomes using isotope-coded affinity tags and mass spectrometry. Proteomics 5(10):2531-2541. doi:10.1002/pmic. 200401198 (Pubitemid 40966480)
225. Paglin S, Lee NY, Nakar C, Fitzgerald M, Plotkin J, Deuel B, Hackett N, McMahill M, Sphicas E, Lampen N, Yahalom J (2005) Rapamycin-sensitive pathway regulates mitochondrial membrane potential, autophagy, and survival in irradiated MCF-7 cells. Cancer Res 65(23):11061-11070. doi:10.1158/0008-5472. CAN-05-1083 (Pubitemid 41713377)
226. Braunstein S, Badura ML, Xi Q, Formenti SC, Schneider RJ (2009) Regulation of protein synthesis by ionizing radiation. Mol Cell Biol 29(21):5645-5656. doi:10.1128/MCB.00711-09
227. Bandhakavi S, Kim YM, Ro SH, Xie H, Onsongo G, Jun CB, Kim DH, Griffin TJ (2010) Quantitative nuclear proteomics identifies mTOR regulation of DNA damage response. Mol Cell Proteomics 9(2):403-414. doi:10.1074/mcp.M900326-MCP200
228. Cam H, Easton JB, High A, Houghton PJ (2010) mTORC1 signaling under hypoxic conditions is controlled by ATM-dependent phosphorylation of HIF-1alpha. Mol Cell 40(4):509-520. doi:10.1016/j.molcel.2010.10.030
229. Moeller BJ, Dewhirst MW (2006) HIF-1 and tumour radiosen-sitivity. Br J Cancer 95(1):1-5. doi:10.1038/sj.bjc.6603201 (Pubitemid 43980546)
230. Guo Z, Deshpande R, Paull TT (2010) ATM activation in the presence of oxidative stress. Cell Cycle 9(24). pii:14323
231. Fu X, Wan S, Lyu YL, Liu LF, Qi H (2008) Etoposide induces ATM-dependent mitochondrial biogenesis through AMPK activation. PLoS One 3(4):e2009. doi:10.1371/journal.pone. 0002009
232. Ambrose M, Goldstine JV, Gatti RA (2007) Intrinsic mito-chondrial dysfunction in ATM-deficient lymphoblastoid cells. Hum Mol Genet 16(18):2154-2164. doi:10.1093/hmg/ddm166 (Pubitemid 47354898)
233. Mao L, Wertzler KJ, Maloney SC, Wang Z, Magnuson NS, Reeves R (2009) HMGA1 levels influence mitochondrial function and mitochondrial DNA repair efficiency. Mol Cell Biol 29(20):5426-5440. doi:10.1128/MCB.00105-09
234. Wuerzberger-Davis SM, Nakamura Y, Seufzer BJ, Miyamoto S (2007) NF-kappaB activation by combinations of NEMO SU-MOylation and ATM activation stresses in the absence of DNA damage. Oncogene 26(5):641-651. doi:10.1038/sj.onc.1209815 (Pubitemid 46204244)
235. Hinz M, Stilmann M, Arslan SC, Khanna KK, Dittmar G, Scheidereit C (2010) A cytoplasmic ATM-TRAF6-cIAP1 module links nuclear DNA damage signaling to ubiquitin-mediated NF-kappaB activation. Mol Cell 40(1):63-74. doi: 10.1016/j.molcel.2010.09.008
236. Volonte D, Kahkonen B, Shapiro S, Di Y, Galbiati F (2009) Caveolin-1 expression is required for the development of pulmonary emphysema through activation of the ATM-p53-p21 pathway. J Biol Chem 284(9):5462-5466. doi:10.1074/jbc.C800 225200
237. Singh S, Sreenath K, Pavithra L, Roy S, Chattopadhyay S (2010) SMAR1 regulates free radical stress through modulation of AKR1a4 enzyme activity. Int J Biochem Cell Biol 42(7): 1105-1114. doi:10.1016/j.biocel.2010.01.022
238. Allen DM, van Praag H, Ray J, Weaver Z, Winrow CJ, Carter TA, Braquet R, Harrington E, Ried T, Brown KD, Gage FH, Barlow C (2001) Ataxia telangiectasia mutated is essential during adult neurogenesis. Genes Dev 15(5):554-566. doi: 10.1101/gad.869001 (Pubitemid 32205144)
239. Carlessi L, De Filippis L, Lecis D, Vescovi A, Delia D (2009) DNA-damage response, survival and differentiation in vitro of a human neural stem cell line in relation to ATM expression. Cell Death Differ 16(6):795-806. doi:10.1038/cdd.2009.10
240. Ito K, Hirao A, Arai F, Matsuoka S, Takubo K, Hamaguchi I, Nomiyama K, Hosokawa K, Sakurada K, Nakagata N, Ikeda Y, Mak TW, Suda T (2004) Regulation of oxidative stress by ATM is required for self-renewal of haematopoietic stem cells. Nature 431(7011):997-1002. doi:10.1038/nature02989 (Pubitemid 39434422)
241. Ito K, Hirao A, Arai F, Takubo K, Matsuoka S, Miyamoto K, Ohmura M, Naka K, Hosokawa K, Ikeda Y, Suda T (2006) Reactive oxygen species act through p38 MAPK to limit the lifespan of hematopoietic stem cells. Nat Med 12(4):446-451. doi:10.1038/nm1388
242. Miyamoto K, Araki KY, Naka K, Arai F, Takubo K, Yamazaki S, Matsuoka S, Miyamoto T, Ito K, Ohmura M, Chen C, Hos-okawa K, Nakauchi H, Nakayama K, Nakayama KI, Harada M, Motoyama N, Suda T, Hirao A (2007) Foxo3a is essential for maintenance of the hematopoietic stem cell pool. Cell Stem Cell 1(1):101-112. doi:10.1016/j.stem.2007.02.001 (Pubitemid 46865800)
243. Yalcin S, Zhang X, Luciano JP, Mungamuri SK, Marinkovic D, Vercherat C, Sarkar A, Grisotto M, Taneja R, Ghaffari S (2008) Foxo3 is essential for the regulation of ataxia telangiectasia mutated and oxidative stress-mediated homeostasis of hemato-poietic stem cells. J Biol Chem 283(37):25692-25705. doi: 10.1074/jbc.M800517200
244. Tsai WB, Chung YM, Takahashi Y, Xu Z, Hu MC (2008) Functional interaction between FOXO3a and ATM regulates DNA damage response. Nat Cell Biol 10(4):460-467. doi: 10.1038/ncb1709
245. Kim J, Wong PK (2009) Loss of ATM impairs proliferation of neural stem cells through oxidative stress-mediated p38 MAPK signaling. Stem Cells 27(8):1987-1998. doi:10.1002/stem.125
246. Kim J, Wong PK (2009) Oxidative stress is linked to ERK1/2-p16 signaling-mediated growth defect in ATM-deficient astrocytes. J Biol Chem 284(21):14396-14404. doi:10.1074/jbc.M808116200
247. Inomata K, Aoto T, Binh NT, Okamoto N, Tanimura S, Wa-kayama T, Iseki S, Hara E, Masunaga T, Shimizu H, Nishimura EK (2009) Genotoxic stress abrogates renewal of melanocyte stem cells by triggering their differentiation. Cell 137(6):1088-1099. doi:10.1016/j.cell.2009.03.037
248. Momcilovic O, Choi S, Varum S, Bakkenist C, Schatten G, Navara C (2009) Ionizing radiation induces ataxia telangiectasia mutated-dependent checkpoint signaling and G(2) but not G(1) cell cycle arrest in pluripotent human embryonic stem cells. Stem Cells 27(8):1822-1835. doi:10.1002/stem.123
249. Adams BR, Golding SE, Rao RR, Valerie K (2010) Dynamic dependence on ATR and ATM for double-strand break repair in human embryonic stem cells and neural descendants. PLoS One 5(4):e10001. doi:10.1371/journal.pone.0010001
250. Armstrong L, Tilgner K, Saretzki G, Atkinson SP, Stojkovic M, Moreno R, Przyborski S, Lako M (2010) Human induced plu-ripotent stem cell lines show stress defense mechanisms and mitochondrial regulation similar to those of human embryonic stem cells. Stem Cells 28(4):661-673. doi:10.1002/stem.307
251. Bar RS, Levis WR, Rechler MM, Harrison LC, Siebert C, Podskalny J, Roth J, Muggeo M (1978) Extreme insulin resistance in ataxia telangiectasia: defect in affinity of insulin receptors. N Engl J Med 298(21):1164-1171. doi:10.1056/ NEJM197805252982103 (Pubitemid 8356481)
252. Peretz S, Jensen R, Baserga R, Glazer PM (2001) ATM-dependent expression of the insulin-like growth factor-I receptor in a pathway regulating radiation response. Proc Natl Acad Sci USA 98(4):1676-1681. doi:10.1073/pnas.041416598 (Pubitemid 32165557)
253. Macaulay VM, Salisbury AJ, Bohula EA, Playford MP, Smorodinsky NI, Shiloh Y (2001) Downregulation of the type 1 insulin-like growth factor receptor in mouse melanoma cells is associated with enhanced radiosensitivity and impaired activation of Atm kinase. Oncogene 20(30):4029-4040. doi:10.1038/ sj.onc.1204565 (Pubitemid 32681608)
254. Yang DQ, Kastan MB (2000) Participation of ATM in insulin signalling through phosphorylation of eIF-4E-binding protein 1. Nat Cell Biol 2(12):893-898. doi:10.1038/35046542
255. Bloch-Damti A, Bashan N (2005) Proposed mechanisms for the induction of insulin resistance by oxidative stress. Antioxid Redox Signal 7(11-12):1553-1567. doi:10.1089/ars.2005.7.1553 (Pubitemid 41767991)
256. Hoehn KL, Salmon AB, Hohnen-Behrens C, Turner N, Hoy AJ, Maghzal GJ, Stocker R, Van Remmen H, Kraegen EW, Cooney GJ, Richardson AR, James DE (2009) Insulin resistance is a cellular antioxidant defense mechanism. Proc Natl Acad Sci USA 106(42):17787-17792. doi:10.1073/pnas.0902380106
257. Ishikawa Y, Otsu K, Oshikawa J (2005) Caveolin; different roles for insulin signal? Cell Signal 17(10):1175-1182. doi: 10.1016/j.cellsig.2005.03.025 (Pubitemid 40982609)
258. Lucero H, Gae D, Taccioli GE (2003) Novel localization of the DNA-PK complex in lipid rafts: a putative role in the signal transduction pathway of the ionizing radiation response. J Biol Chem 278(24):22136-22143. doi:10.1074/jbc.M301579200 (Pubitemid 36792624)
259. Viniegra JG, Martinez N, Modirassari P, Losa JH, Parada Cobo C, Lobo VJ, Luquero CI, Alvarez-Vallina L, Ramon y Cajal S, Rojas JM, Sanchez-Prieto R (2005) Full activation of PKB/Akt in response to insulin or ionizing radiation is mediated through ATM. J Biol Chem 280(6):4029-4036. doi:10.1074/jbc.M4 10344200 (Pubitemid 40288566)
260. Schneider JG, Finck BN, Ren J, Standley KN, Takagi M, Maclean KH, Bernal-Mizrachi C, Muslin AJ, Kastan MB, Semenkovich CF (2006) ATM-dependent suppression of stress signaling reduces vascular disease in metabolic syndrome. Cell Metab 4(5):377-389. doi:10.1016/j.cmet.2006.10.002 (Pubitemid 44645067)
261. Chiu SL, Cline HT (2010) Insulin receptor signaling in the development of neuronal structure and function. Neural Dev 5:7. doi:10.1186/1749-8104-5-7
262. Paganelli R, Scala E, Scarselli E, Ortolani C, Cossarizza A, Carmini D, Aiuti F, Fiorilli M (1992) Selective deficiency of CD4?/CD45RA? lymphocytes in patients with ataxia-telangi-ectasia. J Clin Immunol 12(2):84-91
263. Kondo N, Inoue R, Nishimura S, Kasahara K, Kameyama T, Miwa Y, Lorenzo PR, Orii T (1993) Defective calcium-dependent signal transduction in T lymphocytes of ataxia-telangiectasia. Scand J Immunol 38(1):45-48 (Pubitemid 23196406)
264. Shiloh Y, Tabor E, Becker Y (1982) Colony-forming ability of ataxia-telangiectasia skin fibroblasts is an indicator of their early senescence and increased demand for growth factors. Exp Cell Res 140(1):191-199. doi:0014-4827(82)90169-0[pii] (Pubitemid 13237760)
265. Rhodes N, D'Souza T, Foster CD, Ziv Y, Kirsch DG, Shiloh Y, Kastan MB, Reinhart PH, Gilmer TM (1998) Defective potassium currents in ataxia telangiectasia fibroblasts. Genes Dev 12(23):3686-3692 (Pubitemid 29019649)
266. Khanna KK, Yan J, Watters D, Hobson K, Beamish H, Spring K, Shiloh Y, Gatti RA, Lavin MF (1997) Defective signaling through the B cell antigen receptor in Epstein-Barr virus-transformed ataxia-telangiectasia cells. J Biol Chem 272(14):9489-9495 (Pubitemid 27154965)
267. O'Connor RD, Linthicum DS (1980) Mitogen receptor redistribution defects and concomitant absence of blastogenesis in ataxia-telangiectasia T lymphocytes. Clin Immunol Immuno-pathol 15(1):66-75 (Pubitemid 10170339)
268. Zhang S, Ekman M, Thakur N, Bu S, Davoodpour P, Grimsby S, Tagami S, Heldin CH, Landstrom M (2006) TGFbeta1-induced activation of ATM and p53 mediates apoptosis in a Smad7-dependent manner. Cell Cycle 5(23):2787-2795 3523[pii] (Pubitemid 44901741)
269. Kirshner J, Jobling MF, Pajares MJ, Ravani SA, Glick AB, Lavin MJ, Koslov S, Shiloh Y, Barcellos-Hoff MH (2006) Inhibition of transforming growth factor-beta1 signaling attenuates ataxia telangiectasia mutated activity in response to genotoxic stress. Cancer Res 66(22):10861-10869. doi:10.1158/ 0008-5472.CAN-06-2565 (Pubitemid 44876983)
270. Wiegman EM, Blaese MA, Loeffler H, Coppes RP, Rodemann HP (2007) TGFbeta-1 dependent fast stimulation of ATM and p53 phosphorylation following exposure to ionizing radiation does not involve TGFbeta-receptor I signalling. Radiother Oncol 83(3):289-295. doi:10.1016/j.radonc.2007.05.013 (Pubitemid 46907986)
271. Farooqi AA, Mansoor Q, Rana A, Mashhadi T, Imran M, Naqi S, Bhatti SM (2011) SMURF and NEDD4 interference offers therapeutic potential in chaperoning genome integrity. J Exp Integr Med 1(1). doi:10.5455/jeim.030111.or.002
272. Burdak-Rothkamm S, Short SC, Folkard M, Rothkamm K, Prise KM (2007) ATR-dependent radiation-induced gamma H2AX foci in bystander primary human astrocytes and glioma cells. Oncogene 26(7):993-1002. doi:10.1038/sj.onc.1209863
273. Farooqi Ammad Ahmad MQ, Muhammad Ismail, Shahzad Bhatti (2010) Therapeutic effect of epigallocatechin-3-gallate (EGCG) and silibinin on ATM dynamics in prostate cancer cell line LNCaP. World J Oncol 1(6):242-246
274. Du L, Damoiseaux R, Nahas S, Gao K, Hu H, Pollard JM, Goldstine J, Jung ME, Henning SM, Bertoni C, Gatti RA (2009) Nonaminoglycoside compounds induce readthrough of nonsense mutations. J Exp Med 206(10):2285-2297. doi:10.1084/jem.20 081940