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rdf:type |
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lifeskim:mentions |
umls-concept:C0011155,
umls-concept:C0205263,
umls-concept:C0205460,
umls-concept:C0376571,
umls-concept:C0871261,
umls-concept:C0919532,
umls-concept:C1420865,
umls-concept:C1514873,
umls-concept:C1704632,
umls-concept:C1706817,
umls-concept:C2911692
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pubmed:issue |
4
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pubmed:dateCreated |
2009-8-31
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pubmed:abstractText |
The molecular pathways leading from genomic instability to cellular senescence and/or cell death remain incompletely characterized. Using mouse embryonic fibroblasts with constitutively increased DNA damage due to the absence of the full-length form of the tumor suppressor Brca1 (Brca1(Delta 11/Delta 11)), we show that deletion of p53 binding protein 1 (53BP1) selectivity abrogates senescence and cell death stimulated by reduced Brca1 activity. Furthermore, the embryonic lethality induced by Brca1 mutation can be alleviated by 53BP1 deletion. Adult Brca1(Delta 11/Delta 11)53BP1(-/-) manifest constitutively high levels of genomic instability, yet age relatively normally, with a surprisingly low incidence of overall tumor formation. Together, these in vitro and in vivo data suggest that 53BP1 is specifically required for the development of premature senescence and apoptosis induced by Brca1 deficiency. These observations may have important implications for Brca1-mediated tumor formation as well as for the molecular pathway leading from genomic instability to organismal aging.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/BRCA1 Protein,
http://linkedlifedata.com/resource/pubmed/chemical/Cell Cycle Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Chromosomal Proteins, Non-Histone,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Doxorubicin,
http://linkedlifedata.com/resource/pubmed/chemical/H2AX protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Histones,
http://linkedlifedata.com/resource/pubmed/chemical/Hydrogen Peroxide,
http://linkedlifedata.com/resource/pubmed/chemical/Intracellular Signaling Peptides...,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Serine-Threonine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Trp53bp1 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Suppressor Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/ataxia telangiectasia mutated...,
http://linkedlifedata.com/resource/pubmed/chemical/checkpoint kinase 2
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pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
1097-4164
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pubmed:author |
pubmed-author:BuntingSamuel FSF,
pubmed-author:CaoLongyue LLL,
pubmed-author:ChenJunjieJ,
pubmed-author:DJUM YMY,
pubmed-author:DengChu-XiaCX,
pubmed-author:FinkelTorenT,
pubmed-author:LeeL FLF,
pubmed-author:NussenzweigAndreA,
pubmed-author:PengTie-NanTN,
pubmed-author:WangRui-HongRH,
pubmed-author:WuJ JulieJJ,
pubmed-author:XuXioalingX
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pubmed:issnType |
Electronic
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pubmed:day |
28
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pubmed:volume |
35
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
534-41
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pubmed:dateRevised |
2011-11-17
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pubmed:meshHeading |
pubmed-meshheading:19716796-Aging,
pubmed-meshheading:19716796-Animals,
pubmed-meshheading:19716796-Apoptosis,
pubmed-meshheading:19716796-BRCA1 Protein,
pubmed-meshheading:19716796-Cell Aging,
pubmed-meshheading:19716796-Cell Cycle Proteins,
pubmed-meshheading:19716796-Cell Transformation, Neoplastic,
pubmed-meshheading:19716796-Cells, Cultured,
pubmed-meshheading:19716796-Chromosomal Proteins, Non-Histone,
pubmed-meshheading:19716796-DNA-Binding Proteins,
pubmed-meshheading:19716796-Doxorubicin,
pubmed-meshheading:19716796-Fibroblasts,
pubmed-meshheading:19716796-Gamma Rays,
pubmed-meshheading:19716796-Genomic Instability,
pubmed-meshheading:19716796-Histones,
pubmed-meshheading:19716796-Hydrogen Peroxide,
pubmed-meshheading:19716796-Intracellular Signaling Peptides and Proteins,
pubmed-meshheading:19716796-Mice,
pubmed-meshheading:19716796-Mice, Knockout,
pubmed-meshheading:19716796-Protein-Serine-Threonine Kinases,
pubmed-meshheading:19716796-Tumor Suppressor Proteins
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pubmed:year |
2009
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pubmed:articleTitle |
A selective requirement for 53BP1 in the biological response to genomic instability induced by Brca1 deficiency.
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pubmed:affiliation |
Translational Medicine Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA. liu.cao@nih.gov
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Intramural
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