Source:http://linkedlifedata.com/resource/pubmed/id/15773895
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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
4
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pubmed:dateCreated |
2005-3-18
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pubmed:abstractText |
Yeast Sir2 is a nicotinamide adenine dinucleotide (NAD)-dependent histone deacetylase that plays a central role in transcriptional silencing, chromosomal stability, DNA damage response and aging. In mammals, Sir2-like genes constitute a seven-member family whose function is largely unknown. To investigate the role of the Sir2 family in vertebrates, we have disrupted Sir2 homologues SIRT1 and SIRT2 in the p53-deficient chicken cell line DT40. Both SIRT1-/- and SIRT2-/- cells had mild growth defects. Colony survival assays showed moderate and mild sensitivity to cisplatin in SIRT1-/- and SIRT2-/- cells, respectively, while SIRT1-/-, but not SIRT2-/- cells, were sensitive to ionizing radiation (IR). Cells rendered doubly deficient in SIRT1 and SIRT2 exhibited the same levels of IR and cisplatin sensitivity as SIRT1-/- cells. SIRT1-/- cells appeared to be defective neither in DNA double strand break repair nor in G2/M checkpoints, but were more susceptible to cell death induction following IR than wild-type cells. Furthermore, both SIRT1- and SIRT2-deficient cells were more sensitive to pro-apoptotic stimuli including cisplatin and staurosporine. Our results indicate that SIRT1 and SIRT2 regulate stress-induced cell death pathways in a p53-independent manner.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:month |
Apr
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pubmed:issn |
1356-9597
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
10
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
321-32
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pubmed:dateRevised |
2005-11-17
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pubmed:meshHeading |
pubmed-meshheading:15773895-Animals,
pubmed-meshheading:15773895-Cell Cycle,
pubmed-meshheading:15773895-Cell Death,
pubmed-meshheading:15773895-Cell Line,
pubmed-meshheading:15773895-Cell Survival,
pubmed-meshheading:15773895-Chickens,
pubmed-meshheading:15773895-Chromosome Aberrations,
pubmed-meshheading:15773895-Cisplatin,
pubmed-meshheading:15773895-DNA Damage,
pubmed-meshheading:15773895-DNA Repair,
pubmed-meshheading:15773895-Sirtuins,
pubmed-meshheading:15773895-Tumor Suppressor Protein p53,
pubmed-meshheading:15773895-Ultraviolet Rays,
pubmed-meshheading:15773895-X-Rays
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pubmed:year |
2005
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pubmed:articleTitle |
Role of NAD-dependent deacetylases SIRT1 and SIRT2 in radiation and cisplatin-induced cell death in vertebrate cells.
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pubmed:affiliation |
Department of Immunology and Molecular Genetics, Kawasaki Medical School, 577 Matsushima, Kurashiki, Okayama 701-0192, Japan.
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pubmed:publicationType |
Journal Article
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