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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
8
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pubmed:dateCreated |
2011-2-25
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pubmed:abstractText |
Maintenance of genomic stability depends on the DNA damage response, a biologic barrier in early stages of cancer development. Failure of this response results in genomic instability and high predisposition toward lymphoma, as seen in patients with ataxia-telangiectasia mutated (ATM) dysfunction. ATM activates multiple cell-cycle checkpoints and DNA repair after DNA damage, but its influence on posttranscriptional gene expression has not been examined on a global level. We show that ionizing radiation modulates the dynamic association of the RNA-binding protein HuR with target mRNAs in an ATM-dependent manner, potentially coordinating the genotoxic response as an RNA operon. Pharmacologic ATM inhibition and use of ATM-null cells revealed a critical role for ATM in this process. Numerous mRNAs encoding cancer-related proteins were differentially associated with HuR depending on the functional state of ATM, in turn affecting expression of encoded proteins. The findings presented here reveal a previously unidentified role of ATM in controlling gene expression posttranscriptionally. Dysregulation of this DNA damage response RNA operon is probably relevant to lymphoma development in ataxia-telangiectasia persons. These novel RNA regulatory modules and genetic networks provide critical insight into the function of ATM in oncogenesis.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
AIM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, Surface,
http://linkedlifedata.com/resource/pubmed/chemical/Cell Cycle Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/ELAVL1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Mutant Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Serine-Threonine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/RNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Suppressor Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/ataxia telangiectasia mutated...
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pubmed:status |
MEDLINE
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pubmed:month |
Feb
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pubmed:issn |
1528-0020
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:day |
24
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pubmed:volume |
117
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
2441-50
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pubmed:dateRevised |
2011-11-17
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pubmed:meshHeading |
pubmed-meshheading:21209379-Antigens, Surface,
pubmed-meshheading:21209379-Cell Cycle Proteins,
pubmed-meshheading:21209379-DNA Damage,
pubmed-meshheading:21209379-DNA Repair,
pubmed-meshheading:21209379-DNA-Binding Proteins,
pubmed-meshheading:21209379-Gene Expression Regulation,
pubmed-meshheading:21209379-Gene Regulatory Networks,
pubmed-meshheading:21209379-Humans,
pubmed-meshheading:21209379-Lymphocytes,
pubmed-meshheading:21209379-Lymphoma,
pubmed-meshheading:21209379-Mutant Proteins,
pubmed-meshheading:21209379-Operon,
pubmed-meshheading:21209379-Protein Binding,
pubmed-meshheading:21209379-Protein-Serine-Threonine Kinases,
pubmed-meshheading:21209379-RNA, Messenger,
pubmed-meshheading:21209379-RNA-Binding Proteins,
pubmed-meshheading:21209379-Radiation, Ionizing,
pubmed-meshheading:21209379-Tumor Suppressor Proteins
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pubmed:year |
2011
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pubmed:articleTitle |
ATM regulates a DNA damage response posttranscriptional RNA operon in lymphocytes.
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pubmed:affiliation |
Marlene and Stewart Greenebaum Cancer Center, University of Maryland, Baltimore, MD, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, Non-P.H.S.,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural,
Research Support, N.I.H., Intramural
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