An unusual form of transcriptional silencing in yeast ribosomal DNA.
Jeffrey S. Smith,Jef D. Boeke +1 more
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A novel form of transcriptional silencing in S. cerevisiae in the ribosomal DNA (rDNA) tandem array is identified, suggesting that a specific chromatin structure in rDNA down-regulates polymerase II promoters.Abstract:
Generalized transcriptional repression of large chromosomal regions in Saccharomyces cerevisiae occurs at the silent mating loci and at telomeres and is mediated by the silent information regulator (SIR) genes. We have identified a novel form of transcription al silencing in S. cerevisiae in the ribosomal DNA (rDNA) tandem array. Tyl retrotransposons marked with a weakened URA3 gene (Tyl-mURAS) efficiently integrated into rDNA. The tnURA3 marker in rDNA was transcriptionally silenced in a SIR2-dependent manner. METIS and LEU2 were also partially silenced, indicating that rDNA silencing may be quite general. Deletion of SIR4 enhanced mURA3 and METIS silencing, but deletion of SIRl or SIRS did not affect silencing, indicating that the mechanism of silencing differs from that at telomeres and silent mating loci. Deletion of SIR2 resulted in increased psoralen cross-linking of the rDNA in vivo, suggesting that a specific chromatin structure in rDNA down-regulates polymerase II promoters.read more
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Transcriptional silencing and longevity protein Sir2 is an NAD-dependent histone deacetylase
TL;DR: The analysis of two SIR2 mutations supports the idea that this deacetylase activity accounts for silencing, recombination suppression and extension of life span in vivo, and provides a molecular framework of NAD-dependent histone de acetylation that connects metabolism, genomic silencing and ageing in yeast and, perhaps, in higher eukaryotes.
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The SIR2/3/4 complex and SIR2 alone promote longevity in Saccharomyces cerevisiae by two different mechanisms
TL;DR: It is shown that life span regulation by the Sir proteins is independent of their role in nonhomologous end joining, and increasing the gene dosage extends the life span in wild-type cells.
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Mammalian sirtuins: biological insights and disease relevance.
TL;DR: There have been major advances in the understanding of the enzymology of sirtuins, their regulation, and their ability to broadly improve mammalian physiology and health span, and the challenges that will confront the field in the coming years are discussed.
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Sirtuins in mammals: insights into their biological function
Shaday Michan,David A. Sinclair +1 more
TL;DR: The current understanding of the biological function of the seven mammalian sirtuins, SIRT1-7, is described and their potential as mediators of caloric restriction and as pharmacological targets to delay and treat human age-related diseases are discussed.
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The Sir2 Family of Protein Deacetylases
Gil Blander,Leonard Guarente +1 more
TL;DR: The role of NAD+, the unusual products of the deacetylation reaction, the Sir2 structure, and the Sir1 and Sir2 chemical inhibitors and activators that were recently identified are discussed.
References
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A system of shuttle vectors and yeast host strains designed for efficient manipulation of DNA in Saccharomyces cerevisiae.
Robert S. Sikorski,Philip Hieter +1 more
TL;DR: A series of yeast shuttle vectors and host strains has been created to allow more efficient manipulation of DNA in Saccharomyces cerevisiae to perform most standard DNA manipulations in the same plasmid that is introduced into yeast.
Journal Article
A system of shuttle vectors and yeast host strains designed for efficient manipulation of DNA in Saccharomyces cerevisiae.
Journal ArticleDOI
A positive selection for mutants lacking orotidine-5'-phosphate decarboxylase activity in yeast: 5-fluoro-orotic acid resistance.
TL;DR: Mutations at the URA3 locus of Saccharomyces cerevisiae can be obtained by a positive selection, based on the loss of orotidine-5′-phosphate decarboxylase activity, and seems applicable to a variety of eucaryotic and procaryotic cells.
Book
Methods in Yeast Genetics: A Laboratory Course Manual
TL;DR: An intensive course in yeast genetics has been held at Cold Spring Harbor Laboratory for some years, and the course manual reflects its content and scope as discussed by the authors, with a focus on yeast genetics.