Abstract
Cellular responses to DNA damage are crucial for maintaining homeostasis and preventing the development of cancer. Our understanding of the DNA-damage response has evolved: whereas previously the focus was on DNA repair, we now appreciate that the response to DNA lesions involves a complex, highly branched signaling network. Defects in this response lead to severely debilitating, cancer-predisposing "genomic instability syndromes". Double strand breaks (DSBs) in DNA are potent triggers of the DNA-damage response, which is why they are used to study this pathway. The chief transducer of the DSB signal is the nuclear protein kinase ataxia-telangiectasia mutated (ATM). Genetic, biochemical and structural studies have recently provided insights into the ATM-mediated DSB response, reshaping our view of this signaling pathway while raising new questions.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Acid Anhydride Hydrolases
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Animals
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Ataxia Telangiectasia Mutated Proteins
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Cell Cycle Proteins / physiology*
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Cyclic AMP Response Element-Binding Protein / physiology
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DNA Damage / physiology*
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DNA Repair
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DNA Repair Enzymes / physiology
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DNA-Binding Proteins / physiology*
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Humans
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Intracellular Signaling Peptides and Proteins / physiology
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MRE11 Homologue Protein
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Models, Biological
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Phosphoproteins / physiology
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Protein Serine-Threonine Kinases / physiology*
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Tumor Suppressor Proteins / physiology*
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Tumor Suppressor p53-Binding Protein 1
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Xenopus Proteins / physiology
Substances
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Cell Cycle Proteins
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Cyclic AMP Response Element-Binding Protein
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DNA-Binding Proteins
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Intracellular Signaling Peptides and Proteins
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MRE11 protein, human
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NBN protein, Xenopus
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Phosphoproteins
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TP53BP1 protein, human
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Tumor Suppressor Proteins
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Tumor Suppressor p53-Binding Protein 1
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Xenopus Proteins
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ATM protein, human
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ATR protein, human
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Ataxia Telangiectasia Mutated Proteins
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Protein Serine-Threonine Kinases
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MRE11 Homologue Protein
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Acid Anhydride Hydrolases
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RAD50 protein, human
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DNA Repair Enzymes