Journal ArticleDOI
The Sir2 Family of Protein Deacetylases
Gil Blander,Leonard Guarente +1 more
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TLDR
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.Abstract:
▪ Abstract The yeast SIR protein complex has been implicated in transcription silencing and suppression of recombination. The Sir complex represses transcription at telomeres, mating-type loci, and ribosomal DNA. Unlike SIR3 and SIR4, the SIR2 gene is highly conserved in organisms ranging from archaea to humans. Interestingly, Sir2 is active as an NAD+-dependent deacetylase, which is broadly conserved from bacteria to higher eukaryotes. In this review, we discuss the role of NAD+, the unusual products of the deacetylation reaction, the Sir2 structure, and the Sir2 chemical inhibitors and activators that were recently identified. We summarize the current knowledge of the Sir2 homologs from different organisms, and finally we discuss the role of Sir2 in caloric restriction and aging.read more
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Resveratrol improves health and survival of mice on a high-calorie diet
Joseph A. Baur,Kevin J. Pearson,Nathaniel O Price,Hamish A. Jamieson,Carles Lerin,Avash Kalra,Vinayakumar Prabhu,Joanne S. Allard,Guillermo López-Lluch,Kaitlyn N. Lewis,Paul J. Pistell,Suresh Poosala,Kevin G. Becker,Olivier Boss,Dana M. Gwinn,Mingyi Wang,Sharan Ramaswamy,Kenneth W. Fishbein,Richard G. Spencer,Edward G. Lakatta,David G. Le Couteur,Reuben J. Shaw,Plácido Navas,Pere Puigserver,Donald K. Ingram,Rafael de Cabo,David A. Sinclair +26 more
TL;DR: It is shown that resveratrol shifts the physiology of middle-aged mice on a high-calorie diet towards that of mice onA standard diet and significantly increases their survival and point to new approaches for treating obesity-related disorders and diseases of ageing.
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Mitochondria, Oxidants, and Aging
TL;DR: The evidence is reviewed that both supports and conflicts with the free radical theory of aging and the growing link between mitochondrial metabolism, oxidant formation, and the biology of aging is examined.
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Resveratrol improves mitochondrial function and protects against metabolic disease by activating SIRT1 and PGC-1alpha.
Marie Lagouge,Carmen Argmann,Zachary Gerhart-Hines,Hamid Meziane,Carles Lerin,Frédéric N. Daussin,Nadia Messadeq,Jill C. Milne,Philip D. Lambert,Peter J. Elliott,Bernard Geny,Markku Laakso,Pere Puigserver,Johan Auwerx +13 more
TL;DR: RSV's effects were associated with an induction of genes for oxidative phosphorylation and mitochondrial biogenesis and were largely explained by an RSV-mediated decrease in P GC-1alpha acetylation and an increase in PGC-1 alpha activity.
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Reactive oxygen species, cellular redox systems and apoptosis
Magdalena L. Circu,Tak Yee Aw +1 more
TL;DR: A full understanding of the redox control of apoptotic initiation and execution could underpin the development of therapeutic interventions targeted at oxidative stress-associated disorders.
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Histone deacetylase inhibitors and the promise of epigenetic (and more) treatments for cancer
TL;DR: Investigating aspects of HDACi action both in vitro and in vivo will further improve the design of optimized clinical protocols and help to understand the role of histone deacetylases in tumorigenesis.
References
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Journal ArticleDOI
Crystal structure of the nucleosome core particle at 2.8 Å resolution
TL;DR: The X-ray crystal structure of the nucleosome core particle of chromatin shows in atomic detail how the histone protein octamer is assembled and how 146 base pairs of DNA are organized into a superhelix around it.
Journal ArticleDOI
Small molecule activators of sirtuins extend Saccharomyces cerevisiae lifespan
Konrad T. Howitz,Kevin J. Bitterman,Haim Y. Cohen,Dudley W. Lamming,Siva Lavu,Jason G. Wood,Robert E. Zipkin,Phuong Chung,Anne Kisielewski,Li-Li Zhang,Brandy Scherer,David A. Sinclair +11 more
TL;DR: The potent activator resveratrol, a polyphenol found in red wine, lowers the Michaelis constant of SIRT1 for both the acetylated substrate and NAD+, and increases cell survival by stimulating Sirt1-dependent deacetylation of p53.
Journal ArticleDOI
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.
Journal ArticleDOI
hSIR2SIRT1 Functions as an NAD-Dependent p53 Deacetylase
Homayoun Vaziri,Scott K. Dessain,Scott K. Dessain,Elinor Ng Eaton,Shin-ichiro Imai,Roy A. Frye,Tej K. Pandita,Leonard Guarente,Robert A. Weinberg +8 more
TL;DR: It is proposed that hSir2, the human homolog of the S. cerevisiae Sir2 protein known to be involved in cell aging and in the response to DNA damage, binds and deacetylates the p53 protein with a specificity for its C-terminal Lys382 residue.
Journal ArticleDOI
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.