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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2005-3-18
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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
1356-9597
pubmed:author
pubmed:issnType
Print
pubmed:volume
10
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
321-32
pubmed:dateRevised
2005-11-17
pubmed:meshHeading
pubmed:year
2005
pubmed:articleTitle
Role of NAD-dependent deacetylases SIRT1 and SIRT2 in radiation and cisplatin-induced cell death in vertebrate cells.
pubmed:affiliation
Department of Immunology and Molecular Genetics, Kawasaki Medical School, 577 Matsushima, Kurashiki, Okayama 701-0192, Japan.
pubmed:publicationType
Journal Article