| Direct activation of the ATM protein kinase by the Mre11/Rad50/Nbs1 complex. | |
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MedLine Citation:
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PMID: 15064416 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The complex containing the Mre11, Rad50, and Nbs1 proteins (MRN) is essential for the cellular response to DNA double-strand breaks, integrating DNA repair with the activation of checkpoint signaling through the protein kinase ATM (ataxia telangiectasia mutated). We demonstrate that MRN stimulates the kinase activity of ATM in vitro toward its substrates p53, Chk2, and histone H2AX. MRN makes multiple contacts with ATM and appears to stimulate ATM activity by facilitating the stable binding of substrates. Phosphorylation of Nbs1 is critical for MRN stimulation of ATM activity toward Chk2, but not p53. Kinase-deficient ATM inhibits wild-type ATM phosphorylation of Chk2, consistent with the dominant-negative effect of kinase-deficient ATM in vivo. |
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Authors:
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Ji-Hoon Lee; Tanya T Paull |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: Science (New York, N.Y.) Volume: 304 ISSN: 1095-9203 ISO Abbreviation: Science Publication Date: 2004 Apr |
Date Detail:
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Created Date: 2004-04-05 Completed Date: 2004-04-14 Revised Date: 2011-11-02 |
Medline Journal Info:
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Nlm Unique ID: 0404511 Medline TA: Science Country: United States |
Other Details:
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Languages: eng Pagination: 93-6 Citation Subset: IM |
Affiliation:
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Department of Molecular Genetics and Microbiology, Institute of Cellular and Molecular Biology, University of Texas at Austin, 1 University Station, A4800, Austin, TX 78712, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Ataxia Telangiectasia
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genetics Cell Cycle Proteins / genetics, metabolism* DNA / metabolism DNA Repair Enzymes* DNA-Binding Proteins / metabolism* Enzyme Activation Histones / metabolism Humans Mutation Mutation, Missense Nuclear Proteins / genetics, metabolism* Phosphorylation Protein Binding Protein-Serine-Threonine Kinases / genetics, metabolism* Recombinant Proteins / metabolism Tumor Suppressor Protein p53 / metabolism Tumor Suppressor Proteins |
| Grant Support | |
ID/Acronym/Agency:
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CA94008/CA/NCI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Cell Cycle Proteins; 0/DNA-Binding Proteins; 0/H2AFX protein, human; 0/Histones; 0/MRE11A protein, human; 0/NBN protein, human; 0/Nuclear Proteins; 0/Rad50 protein, human; 0/Recombinant Proteins; 0/Tumor Suppressor Protein p53; 0/Tumor Suppressor Proteins; 9007-49-2/DNA; EC 2.7.1.11/checkpoint kinase 2; EC 2.7.11.1/Protein-Serine-Threonine Kinases; EC 2.7.11.1/ataxia telangiectasia mutated protein; EC 6.5.1.-/DNA Repair Enzymes |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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