title: The SIR2 gene family, conserved from bacteria to humans, functions in silencing, cell cycle progression, and chromosome stability.
abstract: Genomic silencing is a fundamental mechanism of transcriptional regulation, yet little is known about conserved mechanisms of silencing. We report here the discovery of four Saccharomyces cerevisiae homologs of the SIR2 silencing gene (HSTs), as well as conservation of this gene family from bacteria to mammals. At least three HST genes can function in silencing; HST1 overexpression restores transcriptional silencing to a sir2 mutant and hst3 hst4 double mutants are defective in telomeric silencing. In addition, HST3 and HST4 together contribute to proper cell cycle progression, radiation resistance, and genomic stability, establishing new connections between silencing and these fundamental cellular processes.
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002453:Cell Cycle / Q000235:genetics*; D015825:Chromosomes, Fungal; D017124:Conserved Sequence; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics*; D051519:Fibroblast Growth Factor 4; D005346:Fibroblast Growth Factors / Q000737:chemistry / Q000235:genetics; D018628:Gene Dosage; D005786:Gene Expression Regulation; D005800:Genes, Fungal / Q000528:radiation effects; D006655:Histone Deacetylases; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D011518:Proto-Oncogene Proteins / Q000737:chemistry / Q000235:genetics; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000528:radiation effects; D029701:Saccharomyces cerevisiae Proteins; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D038281:Silent Information Regulator Proteins, Saccharomyces cerevisiae; D056564:Sirtuin 1; D056565:Sirtuin 2; D037761:Sirtuins; D016615:Telomere; D013696:Temperature; D015534:Trans-Activators / Q000737:chemistry / Q000235:genetics*; D014158:Transcription, Genetic; D014466:Ultraviolet Rays
chemical_list: D004268:DNA-Binding Proteins; C496445:FGF4 protein, human; D051519:Fibroblast Growth Factor 4; D011518:Proto-Oncogene Proteins; D029701:Saccharomyces cerevisiae Proteins; D038281:Silent Information Regulator Proteins, Saccharomyces cerevisiae; D015534:Trans-Activators; D005346:Fibroblast Growth Factors; C512517:Hst3 protein, S cerevisiae; C512518:Hst4 protein, S cerevisiae; C087778:SIR2 protein, S cerevisiae; C447939:SIRT1 protein, human; D056564:Sirtuin 1; D056565:Sirtuin 2; D037761:Sirtuins; D006655:Histone Deacetylases