Human Molecular Genetics, Vol 7, 1555-1563, Copyright © 1998 by Oxford University Press
G Rotman and Y Shiloh
The identification of ATM , the gene responsible for the pleiotropic
recessive disease ataxia telangiectasia, has initiated extensive research
to determine the functions of its multifaceted protein product. The ATM
protein belongs to a family of protein kinases that share similarities at
their C-terminal region with the catalytic domain of phosphatidylinositol
3-kinases. Studies with ataxia telangiectasia (A-T) cells and Atm-deficient
mice have shown that ATM is a key regulator of multiple signaling cascades
which respond to DNA strand breaks induced by damaging agents or by normal
processes, such as meiotic or V(D)J recombination. These responses involve
the activation of cell cycle checkpoints, DNA repair and apoptosis. Other
roles outside the cell nucleus might be carried out by the cytoplasmic
fraction of ATM. In addition, ATM appears to function as a 'caretaker',
suppressing tumorigenesis in specific T cell lineages.
REVIEWS
ATM: from gene to function
Department of Human Genetics and Molecular Medicine, Sackler School of Medicine, Tel Aviv University, Ramat Aviv 69978, Israel. grotman@ccsg.tau.ac.il
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A. J. R. Bishop, C. Barlow, A. J. Wynshaw-Boris, and R. H. Schiestl Atm Deficiency Causes an Increased Frequency of Intrachromosomal Homologous Recombination in Mice Cancer Res., January 1, 2000; 60(2): 395 - 399. [Abstract] [Full Text]
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R. Khosravi, R. Maya, T. Gottlieb, M. Oren, Y. Shiloh, and D. Shkedy Rapid ATM-dependent phosphorylation of MDM2 precedes p53 accumulation in response to DNA damage PNAS, December 21, 1999; 96(26): 14973 - 14977. [Abstract] [Full Text] [PDF]
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S. Stilgenbauer, D. Winkler, G. Ott, C. Schaffner, E. Leupolt, M. Bentz, P. Moller, H. K. Muller-Hermelink, M. R. James, P. Lichter, et al. Molecular Characterization of 11q Deletions Points to a Pathogenic Role of the ATM Gene in Mantle Cell Lymphoma Blood, November 1, 1999; 94(9): 3262 - 3264. [Abstract] [Full Text] [PDF]
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E. C. Gosink, M. J. Chong, and P. J. McKinnon Ataxia Telangiectasia Mutated Deficiency Affects Astrocyte Growth but not Radiosensitivity Cancer Res., October 1, 1999; 59(20): 5294 - 5298. [Abstract] [Full Text] [PDF]
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F. A. Asimakopoulos, P. J. Shteper, S. Krichevsky, E. Fibach, A. Polliack, E. Rachmilewitz, Y. Ben-Neriah, and D. Ben-Yehuda ABL1 Methylation Is a Distinct Molecular Event Associated With Clonal Evolution of Chronic Myeloid Leukemia Blood, October 1, 1999; 94(7): 2452 - 2460. [Abstract] [Full Text] [PDF]
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G. C. M. Smith, R. B. Cary, N. D. Lakin, B. C. Hann, S.-H. Teo, D. J. Chen, and S. P. Jackson Purification and DNA binding properties of the ataxia-telangiectasia gene product ATM PNAS, September 28, 1999; 96(20): 11134 - 11139. [Abstract] [Full Text] [PDF]
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G. C. M. Smith, F. d'adda di Fagagna, N. D. Lakin, and S. P. Jackson Cleavage and Inactivation of ATM during Apoptosis Mol. Cell. Biol., September 1, 1999; 19(9): 6076 - 6084. [Abstract] [Full Text] [PDF]
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J. N. Sarkaria, E. C. Busby, R. S. Tibbetts, P. Roos, Y. Taya, L. M. Karnitz, and R. T. Abraham Inhibition of ATM and ATR Kinase Activities by the Radiosensitizing Agent, Caffeine Cancer Res., September 1, 1999; 59(17): 4375 - 4382. [Abstract] [Full Text] [PDF]
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C. Barlow, P. A. Dennery, M. K. Shigenaga, M. A. Smith, J. D. Morrow, L. J. Roberts II, A. Wynshaw-Boris, and R. L. Levine Loss of the ataxia-telangiectasia gene product causes oxidative damage in target organs PNAS, August 17, 1999; 96(17): 9915 - 9919. [Abstract] [Full Text] [PDF]
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T. Kamijo, E. van de Kamp, M. J. Chong, F. Zindy, J. A. Diehl, C. J. Sherr, and P. J. McKinnon Loss of the ARF Tumor Suppressor Reverses Premature Replicative Arrest but not Radiation Hypersensitivity Arising from Disabled Atm Function Cancer Res., May 1, 1999; 59(10): 2464 - 2469. [Abstract] [Full Text] [PDF]
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G. C.M. Smith and S. P. Jackson The DNA-dependent protein kinase Genes & Dev., April 15, 1999; 13(8): 916 - 934. [Full Text]
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N. Gueven, K. E. Keating, P. Chen, T. Fukao, K. K. Khanna, D. Watters, P. H. Rodemann, and M. F. Lavin Epidermal Growth Factor Sensitizes Cells to Ionizing Radiation by Down-regulating Protein Mutated in Ataxia-Telangiectasia J. Biol. Chem., March 16, 2001; 276(12): 8884 - 8891. [Abstract] [Full Text] [PDF]
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S. Peretz, R. Jensen, R. Baserga, and P. M. Glazer ATM-dependent expression of the insulin-like growth factor-I receptor in a pathway regulating radiation response PNAS, February 13, 2001; 98(4): 1676 - 1681. [Abstract] [Full Text] [PDF]
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C. Schaffner, I. Idler, S. Stilgenbauer, H. Dohner, and P. Lichter Mantle cell lymphoma is characterized by inactivation of the ATM gene PNAS, March 14, 2000; 97(6): 2773 - 2778. [Abstract] [Full Text] [PDF]
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