title: Hst3 and Hst4 histone deacetylases regulate replicative lifespan by preventing genome instability in Saccharomyces cerevisiae.
abstract: The acetylation of histone H3 on lysine 56 (H3-K56) occurs during S phase and contributes to the processes of DNA damage repair and histone gene transcription. Hst3 and Hst4 have been implicated in the removal of histone H3-K56 acetylation in Saccharomyces cerevisiae. Here, we show that Hst3 and Hst4 regulate the replicative lifespan of S. cerevisiae mother cells. An hst3Δ hst4Δ double-mutant strain, in which acetylation of histone H3-K56 persists throughout the genome during the cell cycle, exhibits genomic instability, which is manifested by a loss of heterozygosity with cell aging. Furthermore, we show that in the absence of other proteins Hst3 and Hst4 can deacetylate nucleosomal histone H3-K56 in a nicotinamide adenine dinucleotide(NAD)(+) -dependent manner. Our results suggest that Hst3 and Hst4 regulate replicative lifespan through their ability to deacetylate histone H3-K56 to minimize genomic instability.
authors.affiliation: Graduate School of Life and Environmental Sciences, Initiative for the Promotion of Young Scientists' Independent Research, University of Tsukuba, Tsukuba, Ibaraki 305-8577, Japan.
authors.forename: Mayumi
authors.initials: M
authors.lastname: Hachinohe
authors.forename: Fumio
authors.initials: F
authors.lastname: Hanaoka
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Masumoto
mesh_terms: D042822:Genomic Instability; D006655:Histone Deacetylases / Q000235:genetics / Q000502:physiology*; D006657:Histones / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000502:physiology*; D038281:Silent Information Regulator Proteins, Saccharomyces cerevisiae / Q000378:metabolism; D056565:Sirtuin 2 / Q000378:metabolism
chemical_list: D006657:Histones; D029701:Saccharomyces cerevisiae Proteins; D038281:Silent Information Regulator Proteins, Saccharomyces cerevisiae; C512517:Hst3 protein, S cerevisiae; C512518:Hst4 protein, S cerevisiae; C087778:SIR2 protein, S cerevisiae; D056565:Sirtuin 2; D006655:Histone Deacetylases