Role of interactions between the origin recognition complex and SIR1 in transcriptional silencing.
Transcriptional silencing of the HM mating-type loci in the yeast Saccharomyces cerevisiae is caused by the localized formation of an altered chromatin structure, analogous to heterochromatin in higher eukaryotes. Silencing depends on cis-acting sequences, termed silencers, as well as several trans-acting factors, including histones H4 and H3, proteins RAP1 and ABF1, and the four SIR proteins (SIR1-4). Each of the four HM silencers contains an autonomously replicating sequence (ARS) to which the origin replication complex (ORC) binds. This six-protein complex is required for initiation of DNA replication, as well as for silencing. Efficient establishment of the silenced state requires both passage through the S phase of the cell cycle and SIR1 protein. Previous experiments suggested that SIR1 might be localized to the silencers by binding to ORC and/or RAP1. Here we report that SIR1 can bind directly to ORC1, the largest of the ORC subunits, and that targeting of SIR1 to ORC1 at a silencer is sufficient to establish a silenced state.
Triolo
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Department of Biochemistry and Cell Biology, State University of New York, Stony Brook, 11794, USA.
Sternglanz
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D004271:DNA, Fungal / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D005656:Fungal Proteins / Q000378:metabolism / Q000502:physiology*; D015966:Gene Expression Regulation, Fungal; D006655:Histone Deacetylases; D008957:Models, Genetic; D009154:Mutation; D011485:Protein Binding; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D018741:Replication Origin / Q000502:physiology*; D012441:Saccharomyces cerevisiae / Q000235:genetics*; D038281:Silent Information Regulator Proteins, Saccharomyces cerevisiae; D056565:Sirtuin 2; D037761:Sirtuins; D015534:Trans-Activators / Q000378:metabolism / Q000502:physiology*; D014158:Transcription, Genetic / Q000502:physiology*
D004271:DNA, Fungal; D004268:DNA-Binding Proteins; D005656:Fungal Proteins; D011993:Recombinant Fusion Proteins; C084121:SIR1 protein, S cerevisiae; C084122:SIR3 protein, S cerevisiae; C061573:SIR4 protein, S cerevisiae; D038281:Silent Information Regulator Proteins, Saccharomyces cerevisiae; D015534:Trans-Activators; C087778:SIR2 protein, S cerevisiae; D056565:Sirtuin 2; D037761:Sirtuins; D006655:Histone Deacetylases