Abstract
The ATM protein has been implicated in pathways controlling cell cycle checkpoints, radiosensitivity, genetic instability, and aging. Expression of ATM fragments containing a leucine zipper motif in a human tumor cell line abrogated the S-phase checkpoint after ionizing irradiation and enhanced radiosensitivity and chromosomal breakage. These fragments did not abrogate irradiation-induced G1 or G2 checkpoints, suggesting that cell cycle checkpoint defects alone cannot account for chromosomal instability in ataxia telangiectasia (AT) cells. Expression of the carboxy-terminal portion of ATM, which contains the PI-3 kinase domain, complemented radiosensitivity and the S-phase checkpoint and reduced chromosomal breakage after irradiation in AT cells. These observations suggest that ATM function is dependent on interactions with itself or other proteins through the leucine zipper region and that the PI-3 kinase domain contains much of the significant activity of ATM.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Ataxia Telangiectasia / genetics
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Ataxia Telangiectasia / physiopathology*
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Ataxia Telangiectasia Mutated Proteins
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Base Sequence
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Cell Cycle / genetics
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Cell Cycle / physiology
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Cell Cycle Proteins
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Cell Survival / genetics
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Cell Survival / physiology
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Chromosome Aberrations
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DNA / biosynthesis
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DNA Damage
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DNA Primers / genetics
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DNA, Complementary / genetics
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DNA-Binding Proteins
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Genes, p53
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Genetic Complementation Test
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Humans
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Leucine Zippers / genetics
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Leucine Zippers / physiology
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Peptide Fragments / genetics
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Peptide Fragments / physiology
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Phenotype
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Phosphatidylinositol 3-Kinases
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Phosphotransferases (Alcohol Group Acceptor) / genetics
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Phosphotransferases (Alcohol Group Acceptor) / physiology
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Protein Serine-Threonine Kinases*
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Proteins / genetics*
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Proteins / physiology*
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Radiation Tolerance / genetics
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Radiation Tolerance / physiology
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Tumor Suppressor Proteins
Substances
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Cell Cycle Proteins
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DNA Primers
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DNA, Complementary
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DNA-Binding Proteins
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Peptide Fragments
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Proteins
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Tumor Suppressor Proteins
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DNA
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Phosphotransferases (Alcohol Group Acceptor)
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ATM protein, human
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Ataxia Telangiectasia Mutated Proteins
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Protein Serine-Threonine Kinases