title: Mutations in Saccharomyces cerevisiae gene SIR2 can have differential effects on in vivo silencing phenotypes and in vitro histone deacetylation activity.
abstract: The yeast SIR2 gene and many of its homologs have been identified as NAD(+)-dependent histone deacetylases. To get a broader view of the relationship between the histone deacetylase activity of Sir2p and its in vivo functions we have mutated eight highly conserved residues in the core domain of SIR2. These mutations have a range of effects on the ability of Sir2p to deacetylate histones in vitro and to silence genes at the telomeres and HM loci. Interestingly, there is not a direct correlation between the in vitro and in vivo effects in some of these mutations. We also show that the histone deacetylase activity of Sir2p is necessary for the proper localiztion of the SIR complex to the telomeres.
authors.affiliation: Department of Biology, Massachussetts Institute of Technology, Cambridge, MA 02139, USA.
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Armstrong
authors.forename: Matt
authors.initials: M
authors.lastname: Kaeberlein
authors.forename: Shin Ichiro
authors.initials: SI
authors.lastname: Imai
authors.forename: Leonard
authors.initials: L
authors.lastname: Guarente
mesh_terms: D000595:Amino Acid Sequence; D002843:Chromatin / Q000378:metabolism; D020868:Gene Silencing; D006655:Histone Deacetylases / Q000235:genetics* / Q000378:metabolism; D006657:Histones / Q000378:metabolism; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009154:Mutation; D010641:Phenotype; D010957:Plasmids / Q000378:metabolism; D011233:Precipitin Tests; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000378:metabolism; D011995:Recombination, Genetic; D012441:Saccharomyces cerevisiae / Q000235:genetics*; D017386:Sequence Homology, Amino Acid; D038281:Silent Information Regulator Proteins, Saccharomyces cerevisiae; D056565:Sirtuin 2; D037761:Sirtuins; D016615:Telomere / Q000378:metabolism; D013997:Time Factors; D015534:Trans-Activators / Q000235:genetics*
chemical_list: D002843:Chromatin; D006657:Histones; D011994:Recombinant Proteins; D038281:Silent Information Regulator Proteins, Saccharomyces cerevisiae; D015534:Trans-Activators; C087778:SIR2 protein, S cerevisiae; D056565:Sirtuin 2; D037761:Sirtuins; D006655:Histone Deacetylases