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Gene Review

ATM  -  ATM serine/threonine kinase

Homo sapiens

Synonyms: A-T mutated, AT1, ATA, ATC, ATD, ...
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Disease relevance of ATM


Psychiatry related information on ATM


High impact information on ATM

  • The ATM gene is related to a family of genes involved in cellular responses to DNA damage and/or cell cycle control [15].
  • Recent findings related to the role of intrarenally formed angiotensin II and the prominence of the AT1 receptors are described [16].
  • Paradoxically, telomere function depends on checkpoint proteins such as ATM and ATR, but a molecular model explaining this seemingly contradictory relationship has been missing so far [17].
  • Second, after replication, telomeres attract ATM and the homologous recombination (HR) machinery [17].
  • There was no evidence that other classes of ATM variant confer a risk of breast cancer [18].

Chemical compound and disease context of ATM


Biological context of ATM


Anatomical context of ATM


Associations of ATM with chemical compounds


Physical interactions of ATM

  • The 400 kDa subunit of the PCAF histone acetylase complex belongs to the ATM superfamily [38].
  • The Mre11 complex is required for ATM activation and the G2/M checkpoint [4].
  • Indole-3-carbinol activates the ATM signaling pathway independent of DNA damage to stabilize p53 and induce G1 arrest of human mammary epithelial cells [39].
  • These results demonstrate that the Mre11 complex can function as a damage sensor upstream of ATM/ATR signaling in mammalian cells [4].
  • ATM forms a stable complex with Tip60 through the conserved FATC domain of ATM [5].

Enzymatic interactions of ATM


Co-localisations of ATM

  • Here, we show that both endogenous and overexpressed human BLM accumulates at sites of laser light-induced DNA double-strand breaks within 10s and colocalizes with gammaH2AX and ATM [45].
  • Large foci containing phosphorylated ATM and gamma-H2AX co-localized and foci with p53 phosphorylated at serine 15 also showed the same distribution [46].

Regulatory relationships of ATM


Other interactions of ATM


Analytical, diagnostic and therapeutic context of ATM

  • These results indicate that RAD53 is a signal transducer in the DNA damage and replication checkpoint pathways and functions downstream of two members of the ATM lipid kinase family [56].
  • Here we show that RPA2 phosphorylation is delayed in cells deficient in one of these kinases and completely abolished in wild-type, ATM, or DNA-PK-deficient cells after treatment with wortmannin at a concentration-inhibiting ATM and DNA-PK [44].
  • We describe an in vitro immunoprecipitation system demonstrating activation of ATM kinase from unirradiated extracts by preincubation with ATP [57].
  • Taken together these data implicate both ATR and ATM as critical roles in the response of hypoxia and reperfusion in solid tumors [58].
  • Electron microscopy and 3D reconstructions reveal that human ATM kinase uses an arm-like domain to clamp around double-stranded DNA [59].


  1. ATM-dependent phosphorylation of nibrin in response to radiation exposure. Gatei, M., Young, D., Cerosaletti, K.M., Desai-Mehta, A., Spring, K., Kozlov, S., Lavin, M.F., Gatti, R.A., Concannon, P., Khanna, K. Nat. Genet. (2000) [Pubmed]
  2. PPM1D dephosphorylates Chk1 and p53 and abrogates cell cycle checkpoints. Lu, X., Nannenga, B., Donehower, L.A. Genes Dev. (2005) [Pubmed]
  3. A new effector pathway links ATM kinase with the DNA damage response. Demonacos, C., Krstic-Demonacos, M., Smith, L., Xu, D., O'Connor, D.P., Jansson, M., La Thangue, N.B. Nat. Cell Biol. (2004) [Pubmed]
  4. The Mre11 complex is required for ATM activation and the G2/M checkpoint. Carson, C.T., Schwartz, R.A., Stracker, T.H., Lilley, C.E., Lee, D.V., Weitzman, M.D. EMBO J. (2003) [Pubmed]
  5. A role for the Tip60 histone acetyltransferase in the acetylation and activation of ATM. Sun, Y., Jiang, X., Chen, S., Fernandes, N., Price, B.D. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  6. Hyperthermia activates a subset of ataxia-telangiectasia mutated effectors independent of DNA strand breaks and heat shock protein 70 status. Hunt, C.R., Pandita, R.K., Laszlo, A., Higashikubo, R., Agarwal, M., Kitamura, T., Gupta, A., Rief, N., Horikoshi, N., Baskaran, R., Lee, J.H., Löbrich, M., Paull, T.T., Roti Roti, J.L., Pandita, T.K. Cancer Res. (2007) [Pubmed]
  7. ATMIN defines an NBS1-independent pathway of ATM signalling. Kanu, N., Behrens, A. EMBO J. (2007) [Pubmed]
  8. Fanconi anemia pathway-deficient tumor cells are hypersensitive to inhibition of ataxia telangiectasia mutated. Kennedy, R.D., Chen, C.C., Stuckert, P., Archila, E.M., De la Vega, M.A., Moreau, L.A., Shimamura, A., D'Andrea, A.D. J. Clin. Invest. (2007) [Pubmed]
  9. ATM kinase activity modulates Fas sensitivity through the regulation of FLIP in lymphoid cells. Stagni, V., di Bari, M.G., Cursi, S., Condò, I., Cencioni, M.T., Testi, R., Lerenthal, Y., Cundari, E., Barilà, D. Blood (2008) [Pubmed]
  10. DNA damage induced by polyglutamine-expanded proteins. Giuliano, P., De Cristofaro, T., Affaitati, A., Pizzulo, G.M., Feliciello, A., Criscuolo, C., De Michele, G., Filla, A., Avvedimento, E.V., Varrone, S. Hum. Mol. Genet. (2003) [Pubmed]
  11. Age-related effects of blocked and random practice schedules on learning a new technology. Jamieson, B.A., Rogers, W.A. The journals of gerontology. Series B, Psychological sciences and social sciences. (2000) [Pubmed]
  12. Disorders of spinal cord, nerve, and muscle. Shafer, S.Q. Neurologic clinics. (1993) [Pubmed]
  13. Predicting competency in automated machine use in an acquired brain injury population using neuropsychological measures. Crowe, S.F., Mahony, K., Jackson, M. Archives of clinical neuropsychology : the official journal of the National Academy of Neuropsychologists. (2004) [Pubmed]
  14. The ataxia-oculomotor apraxia 1 gene product has a role distinct from ATM and interacts with the DNA strand break repair proteins XRCC1 and XRCC4. Clements, P.M., Breslin, C., Deeks, E.D., Byrd, P.J., Ju, L., Bieganowski, P., Brenner, C., Moreira, M.C., Taylor, A.M., Caldecott, K.W. DNA Repair (Amst.) (2004) [Pubmed]
  15. The genetic defect in ataxia-telangiectasia. Lavin, M.F., Shiloh, Y. Annu. Rev. Immunol. (1997) [Pubmed]
  16. Paracrine regulation of the renal microcirculation. Navar, L.G., Inscho, E.W., Majid, S.A., Imig, J.D., Harrison-Bernard, L.M., Mitchell, K.D. Physiol. Rev. (1996) [Pubmed]
  17. The DNA damage machinery and homologous recombination pathway act consecutively to protect human telomeres. Verdun, R.E., Karlseder, J. Cell (2006) [Pubmed]
  18. ATM mutations that cause ataxia-telangiectasia are breast cancer susceptibility alleles. Renwick, A., Thompson, D., Seal, S., Kelly, P., Chagtai, T., Ahmed, M., North, B., Jayatilake, H., Barfoot, R., Spanova, K., McGuffog, L., Evans, D.G., Eccles, D., Easton, D.F., Stratton, M.R., Rahman, N. Nat. Genet. (2006) [Pubmed]
  19. DNA damage-induced cell cycle regulation and function of novel chk2 phosphoresidues. Buscemi, G., Carlessi, L., Zannini, L., Lisanti, S., Fontanella, E., Canevari, S., Delia, D. Mol. Cell. Biol. (2006) [Pubmed]
  20. Stalled replication induces p53 accumulation through distinct mechanisms from DNA damage checkpoint pathways. Ho, C.C., Siu, W.Y., Lau, A., Chan, W.M., Arooz, T., Poon, R.Y. Cancer Res. (2006) [Pubmed]
  21. Genistein arrests hepatoma cells at G2/M phase: involvement of ATM activation and upregulation of p21waf1/cip1 and Wee1. Chang, K.L., Kung, M.L., Chow, N.H., Su, S.J. Biochem. Pharmacol. (2004) [Pubmed]
  22. CHK1 and CHK2 are differentially involved in mismatch repair-mediated 6-thioguanine-induced cell cycle checkpoint responses. Yan, T., Desai, A.B., Jacobberger, J.W., Sramkoski, R.M., Loh, T., Kinsella, T.J. Mol. Cancer Ther. (2004) [Pubmed]
  23. N-methyl-N'-nitro-N-nitrosoguanidine activates cell-cycle arrest through distinct mechanisms activated in a dose-dependent manner. Beardsley, D.I., Kim, W.J., Brown, K.D. Mol. Pharmacol. (2005) [Pubmed]
  24. Human telomeric protein TRF2 associates with genomic double-strand breaks as an early response to DNA damage. Bradshaw, P.S., Stavropoulos, D.J., Meyn, M.S. Nat. Genet. (2005) [Pubmed]
  25. Linkage of ATM to cell cycle regulation by the Chk2 protein kinase. Matsuoka, S., Huang, M., Elledge, S.J. Science (1998) [Pubmed]
  26. p53- and ATM-dependent apoptosis induced by telomeres lacking TRF2. Karlseder, J., Broccoli, D., Dai, Y., Hardy, S., de Lange, T. Science (1999) [Pubmed]
  27. Functional interactions between BRCA1 and the checkpoint kinase ATR during genotoxic stress. Tibbetts, R.S., Cortez, D., Brumbaugh, K.M., Scully, R., Livingston, D., Elledge, S.J., Abraham, R.T. Genes Dev. (2000) [Pubmed]
  28. Cleavage of Cdc6 by caspase-3 promotes ATM/ATR kinase-mediated apoptosis of HeLa cells. Yim, H., Hwang, I.S., Choi, J.S., Chun, K.H., Jin, Y.H., Ham, Y.M., Lee, K.Y., Lee, S.K. J. Cell Biol. (2006) [Pubmed]
  29. Phosphorylation of serines 635 and 645 of human Rad17 is cell cycle regulated and is required for G(1)/S checkpoint activation in response to DNA damage. Post, S., Weng, Y.C., Cimprich, K., Chen, L.B., Xu, Y., Lee, E.Y. Proc. Natl. Acad. Sci. U.S.A. (2001) [Pubmed]
  30. Identification and characterization of polymorphic variations of the ataxia telangiectasia mutated (ATM) gene in childhood Hodgkin disease. Takagi, M., Tsuchida, R., Oguchi, K., Shigeta, T., Nakada, S., Shimizu, K., Ohki, M., Delia, D., Chessa, L., Taya, Y., Nakanishi, M., Tsunematsu, Y., Bessho, F., Isoyama, K., Hayashi, Y., Kudo, K., Okamura, J., Mizutani, S. Blood (2004) [Pubmed]
  31. Mutations in the ATM gene lead to impaired overall and treatment-free survival that is independent of IGVH mutation status in patients with B-CLL. Austen, B., Powell, J.E., Alvi, A., Edwards, I., Hooper, L., Starczynski, J., Taylor, A.M., Fegan, C., Moss, P., Stankovic, T. Blood (2005) [Pubmed]
  32. ATM mutations are associated with inactivation of the ARF-TP53 tumor suppressor pathway in diffuse large B-cell lymphoma. Grønbaek, K., Worm, J., Ralfkiaer, E., Ahrenkiel, V., Hokland, P., Guldberg, P. Blood (2002) [Pubmed]
  33. ATM phosphorylation of Nijmegen breakage syndrome protein is required in a DNA damage response. Wu, X., Ranganathan, V., Weisman, D.S., Heine, W.F., Ciccone, D.N., O'Neill, T.B., Crick, K.E., Pierce, K.A., Lane, W.S., Rathbun, G., Livingston, D.M., Weaver, D.T. Nature (2000) [Pubmed]
  34. Threonine 68 is required for radiation-induced phosphorylation and activation of Cds1. Melchionna, R., Chen, X.B., Blasina, A., McGowan, C.H. Nat. Cell Biol. (2000) [Pubmed]
  35. Inhibition of human Chk1 causes increased initiation of DNA replication, phosphorylation of ATR targets, and DNA breakage. Syljuåsen, R.G., Sørensen, C.S., Hansen, L.T., Fugger, K., Lundin, C., Johansson, F., Helleday, T., Sehested, M., Lukas, J., Bartek, J. Mol. Cell. Biol. (2005) [Pubmed]
  36. Differentiation-induced radioresistance in muscle cells. Latella, L., Lukas, J., Simone, C., Puri, P.L., Bartek, J. Mol. Cell. Biol. (2004) [Pubmed]
  37. Down-regulation of ATM protein in HRS cells of nodular sclerosis Hodgkin's lymphoma in children occurs in the absence of ATM gene inactivation. Bose, S., Starczynski, J., Chukwuma, M., Baumforth, K., Wei, W., Morgan, S., Byrd, P., Ying, J., Grundy, R., Mann, J.R., Tao, Q., Taylor, A.M., Murray, P.G., Stankovic, T. J. Pathol. (2007) [Pubmed]
  38. The 400 kDa subunit of the PCAF histone acetylase complex belongs to the ATM superfamily. Vassilev, A., Yamauchi, J., Kotani, T., Prives, C., Avantaggiati, M.L., Qin, J., Nakatani, Y. Mol. Cell (1998) [Pubmed]
  39. Indole-3-carbinol activates the ATM signaling pathway independent of DNA damage to stabilize p53 and induce G1 arrest of human mammary epithelial cells. Brew, C.T., Aronchik, I., Hsu, J.C., Sheen, J.H., Dickson, R.B., Bjeldanes, L.F., Firestone, G.L. Int. J. Cancer (2006) [Pubmed]
  40. Tumor suppressor p53 binding protein 1 (53BP1) is involved in DNA damage-signaling pathways. Rappold, I., Iwabuchi, K., Date, T., Chen, J. J. Cell Biol. (2001) [Pubmed]
  41. Ataxia telangiectasia-mutated phosphorylates Chk2 in vivo and in vitro. Matsuoka, S., Rotman, G., Ogawa, A., Shiloh, Y., Tamai, K., Elledge, S.J. Proc. Natl. Acad. Sci. U.S.A. (2000) [Pubmed]
  42. Minichromosome maintenance proteins are direct targets of the ATM and ATR checkpoint kinases. Cortez, D., Glick, G., Elledge, S.J. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  43. Histone H2A phosphorylation controls Crb2 recruitment at DNA breaks, maintains checkpoint arrest, and influences DNA repair in fission yeast. Nakamura, T.M., Du, L.L., Redon, C., Russell, P. Mol. Cell. Biol. (2004) [Pubmed]
  44. Replication protein A2 phosphorylation after DNA damage by the coordinated action of ataxia telangiectasia-mutated and DNA-dependent protein kinase. Wang, H., Guan, J., Wang, H., Perrault, A.R., Wang, Y., Iliakis, G. Cancer Res. (2001) [Pubmed]
  45. BLM is an early responder to DNA double-strand breaks. Karmakar, P., Seki, M., Kanamori, M., Hashiguchi, K., Ohtsuki, M., Murata, E., Inoue, E., Tada, S., Lan, L., Yasui, A., Enomoto, T. Biochem. Biophys. Res. Commun. (2006) [Pubmed]
  46. Interstitial chromatin alteration causes persistent p53 activation involved in the radiation-induced senescence-like growth arrest. Suzuki, M., Suzuki, K., Kodama, S., Watanabe, M. Biochem. Biophys. Res. Commun. (2006) [Pubmed]
  47. ATM regulates ATR chromatin loading in response to DNA double-strand breaks. Cuadrado, M., Martinez-Pastor, B., Murga, M., Toledo, L.I., Gutierrez-Martinez, P., Lopez, E., Fernandez-Capetillo, O. J. Exp. Med. (2006) [Pubmed]
  48. The hCds1 (Chk2)-FHA domain is essential for a chain of phosphorylation events on hCds1 that is induced by ionizing radiation. Lee, C.H., Chung, J.H. J. Biol. Chem. (2001) [Pubmed]
  49. Regulation of the IRF-1 tumour modifier during the response to genotoxic stress involves an ATM-dependent signalling pathway. Pamment, J., Ramsay, E., Kelleher, M., Dornan, D., Ball, K.L. Oncogene (2002) [Pubmed]
  50. Activation of the kinase activity of ATM by retinoic acid is required for CREB-dependent differentiation of neuroblastoma cells. Fernandes, N.D., Sun, Y., Price, B.D. J. Biol. Chem. (2007) [Pubmed]
  51. Coregulated ataxia telangiectasia-mutated and casein kinase sites modulate cAMP-response element-binding protein-coactivator interactions in response to DNA damage. Shanware, N.P., Trinh, A.T., Williams, L.M., Tibbetts, R.S. J. Biol. Chem. (2007) [Pubmed]
  52. Foxo3 is essential for the regulation of ataxia telangiectasia mutated and oxidative stress-mediated homeostasis of hematopoietic stem cells. Yalcin, S., Zhang, X., Luciano, J.P., Mungamuri, S.K., Marinkovic, D., Vercherat, C., Sarkar, A., Grisotto, M., Taneja, R., Ghaffari, S. J. Biol. Chem. (2008) [Pubmed]
  53. ATR/ATM-mediated phosphorylation of human Rad17 is required for genotoxic stress responses. Bao, S., Tibbetts, R.S., Brumbaugh, K.M., Fang, Y., Richardson, D.A., Ali, A., Chen, S.M., Abraham, R.T., Wang, X.F. Nature (2001) [Pubmed]
  54. MDC1 accelerates nonhomologous end-joining of dysfunctional telomeres. Dimitrova, N., de Lange, T. Genes Dev. (2006) [Pubmed]
  55. Aven-dependent activation of ATM following DNA damage. Guo, J.Y., Yamada, A., Kajino, T., Wu, J.Q., Tang, W., Freel, C.D., Feng, J., Chau, B.N., Wang, M.Z., Margolis, S.S., Yoo, H.Y., Wang, X.F., Dunphy, W.G., Irusta, P.M., Hardwick, J.M., Kornbluth, S. Curr. Biol. (2008) [Pubmed]
  56. Regulation of RAD53 by the ATM-like kinases MEC1 and TEL1 in yeast cell cycle checkpoint pathways. Sanchez, Y., Desany, B.A., Jones, W.J., Liu, Q., Wang, B., Elledge, S.J. Science (1996) [Pubmed]
  57. ATP activates ataxia-telangiectasia mutated (ATM) in vitro. Importance of autophosphorylation. Kozlov, S., Gueven, N., Keating, K., Ramsay, J., Lavin, M.F. J. Biol. Chem. (2003) [Pubmed]
  58. ATR/ATM targets are phosphorylated by ATR in response to hypoxia and ATM in response to reoxygenation. Hammond, E.M., Dorie, M.J., Giaccia, A.J. J. Biol. Chem. (2003) [Pubmed]
  59. Electron microscopy and 3D reconstructions reveal that human ATM kinase uses an arm-like domain to clamp around double-stranded DNA. Llorca, O., Rivera-Calzada, A., Grantham, J., Willison, K.R. Oncogene (2003) [Pubmed]
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