Source:http://linkedlifedata.com/resource/pubmed/id/15459124
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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
15
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pubmed:dateCreated |
2004-12-3
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pubmed:abstractText |
Werner syndrome (WS) is a rare disease caused by the lack of a functional nuclear WS protein (WRN). WS is characterized by the early onset of premature aging signs and a high incidence of sarcomas. WS diploid fibroblasts have a short life span and extensive genomic instability. Mammalian cells are continuously exposed to reactive oxygen species (ROS), which represent human mutagens and are thought to be a major contributor to the aging process. Hydrogen peroxide (H2O2) is a common ROS intermediate generated by various forms of oxidative stress. In response to H2O2-induced DNA damage, normal human diploid fibroblasts follow a pathway leading to irreversible proliferation arrest and premature senescence. Here we show that in contrast to normal human fibroblasts, WS diploid fibroblasts continue proliferating after extensive H2O2-induced DNA damage and accumulate oxidative DNA lesions. A direct role of WRN in this abnormal cellular response to H2O2 is demonstrated by interfering with WRN expression in normal human fibroblasts. We propose a role for WRN in the detection and/or processing of oxidative DNA lesions and in cellular responses to H2O2 as they relate to some of the phenotypical aspects of WS cells.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/DNA,
http://linkedlifedata.com/resource/pubmed/chemical/DNA Helicases,
http://linkedlifedata.com/resource/pubmed/chemical/Exodeoxyribonucleases,
http://linkedlifedata.com/resource/pubmed/chemical/Hydrogen Peroxide,
http://linkedlifedata.com/resource/pubmed/chemical/RecQ Helicases,
http://linkedlifedata.com/resource/pubmed/chemical/WRN protein, human
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pubmed:status |
MEDLINE
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pubmed:month |
Dec
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pubmed:issn |
1530-6860
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pubmed:author | |
pubmed:issnType |
Electronic
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pubmed:volume |
18
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1970-2
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pubmed:dateRevised |
2008-11-21
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pubmed:meshHeading |
pubmed-meshheading:15459124-Cell Aging,
pubmed-meshheading:15459124-Cell Death,
pubmed-meshheading:15459124-Cell Proliferation,
pubmed-meshheading:15459124-Cells, Cultured,
pubmed-meshheading:15459124-DNA,
pubmed-meshheading:15459124-DNA Damage,
pubmed-meshheading:15459124-DNA Helicases,
pubmed-meshheading:15459124-Exodeoxyribonucleases,
pubmed-meshheading:15459124-Fibroblasts,
pubmed-meshheading:15459124-Humans,
pubmed-meshheading:15459124-Hydrogen Peroxide,
pubmed-meshheading:15459124-Oxidation-Reduction,
pubmed-meshheading:15459124-RecQ Helicases,
pubmed-meshheading:15459124-Werner Syndrome
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pubmed:year |
2004
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pubmed:articleTitle |
Werner syndrome cells escape hydrogen peroxide-induced cell proliferation arrest.
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pubmed:affiliation |
Laboratory of Molecular Gerontology, National Institute on Aging, NIH, Baltimore, Maryland 21224, USA.
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pubmed:publicationType |
Journal Article
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