Abstract
Maintenance of genome stability is essential for avoiding the passage to neoplasia. The DNA-damage response--a cornerstone of genome stability--occurs by a swift transduction of the DNA-damage signal to many cellular pathways. A prime example is the cellular response to DNA double-strand breaks, which activate the ATM protein kinase that, in turn, modulates numerous signalling pathways. ATM mutations lead to the cancer-predisposing genetic disorder ataxia-telangiectasia (A-T). Understanding ATM's mode of action provides new insights into the association between defective responses to DNA damage and cancer, and brings us closer to resolving the issue of cancer predisposition in some A-T carriers.
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.
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Review
MeSH terms
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Animals
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Ataxia Telangiectasia / enzymology
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Ataxia Telangiectasia / genetics*
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Ataxia Telangiectasia Mutated Proteins
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Cell Cycle Proteins
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Cell Transformation, Neoplastic / genetics*
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Chromosome Breakage
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DNA Damage
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DNA Repair / genetics
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DNA Repair / physiology*
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DNA-Binding Proteins
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Enzyme Activation
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Genes, cdc
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Genetic Predisposition to Disease
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Humans
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Mice
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Mice, Knockout
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Models, Genetic
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Multigene Family
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Neoplastic Syndromes, Hereditary / enzymology
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Neoplastic Syndromes, Hereditary / genetics
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Phosphatidylinositol 3-Kinases / physiology
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Protein Serine-Threonine Kinases / deficiency
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Protein Serine-Threonine Kinases / genetics
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Protein Serine-Threonine Kinases / physiology*
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Signal Transduction
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Tumor Suppressor Proteins
Substances
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Cell Cycle Proteins
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DNA-Binding Proteins
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Tumor Suppressor Proteins
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ATM protein, human
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Ataxia Telangiectasia Mutated Proteins
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Atm protein, mouse
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Protein Serine-Threonine Kinases