Evidence for ORC-dependent repression of budding yeast genes induced by starvation and other stresses

Department of Cell Stress Biology and Roswell Park Cancer Institute, Buffalo, NY 14263, USA.
FEMS Yeast Research (Impact Factor: 2.82). 09/2006; 6(5):763-76. DOI: 10.1111/j.1567-1364.2006.00077.x
Source: PubMed


The highly conserved origin recognition complex (ORC) is required for repressing genes in the silent mating type loci of budding yeast. Here we report that at a non-permissive temperature, the temperature-sensitive orc2-1 mutation induces the expression of more than 500 genes, the majority of which are also induced during starvation of wild-type cells. Many genes induced by starvation or by the orc2-1 mutation are also induced by inactivation of proteins required for chromatin-mediated repression of transcription. Genes induced by the orc2-1 mutation, starvation, or inactivation of repressor proteins, map near ORC-binding loci significantly more frequently compared to all genes. Genes repressed by starvation map near ORC-binding sites less frequently compared to all genes, which suggests they have been evolutionarily excluded from regions of repressive chromatin near ORC-binding sites. Deletion of sequences containing ORC-binding sites near the DAL2 and DAL4 genes in the DAL gene cluster, which are induced by either the orc2-1 mutation or by starvation, constitutively activates these genes and abolishes their activation by the orc2-1 mutation. Our findings suggest a role for ORC in the repression of a large number of budding yeast genes induced by starvation or other aspects of a deleterious environment.

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Available from: Ping Liang, Oct 14, 2014
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    • "On the other hand, Orc2p is a subunit of the origin recognition complex (ORC) that functions in pre-replication complex formation [29] and in chromatin silencing at telomere [16]. Interestingly, Orc2p also functions in the transcriptional regulation of stress-responsive genes, acting as a repressor [30,31] or an activator able to induce expression of highly transcribed genes positioned nearby ORCs [15]. Nevertheless, more work is needed to establish the functional connections between overexpression of CAF16 and ORC2 and ion and freeze tolerance in high-sucrose dough. "
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    ABSTRACT: Recent years have seen a huge growth in the market of industrial yeasts with the need for strains affording better performance or to be used in new applications. Stress tolerance of commercial Saccharomyces cerevisiae yeasts is, without doubt, a trait that needs improving. Such trait is, however, complex, and therefore only in-depth knowledge of their biochemical, physiological and genetic principles can help us to define improvement strategies and to identify the key factors for strain selection. We have determined the transcriptional response of commercial baker's yeast cells to both high-sucrose and lean dough by using DNA macroarrays and liquid dough (LD) model system. Cells from compressed yeast blocks display a reciprocal transcription program to that commonly reported for laboratory strains exposed to osmotic stress. This discrepancy likely reflects differences in strain background and/or experimental design. Quite remarkably, we also found that the transcriptional response of starved baker's yeast cells was qualitatively similar in the presence or absence of sucrose in the LD. Nevertheless, there was a set of differentially regulated genes, which might be relevant for cells to adapt to high osmolarity. Consistent with this, overexpression of CAF16 or ORC2, two transcriptional factor-encoding genes included in this group, had positive effects on leavening activity of baker's yeast. Moreover, these effects were more pronounced during freezing and frozen storage of high-sucrose LD. Engineering of differentially regulated genes opens the possibility to improve the physiological behavior of baker's yeast cells under stress conditions like those encountered in downstream applications.
    Microbial Cell Factories 07/2010; 9(1):56. DOI:10.1186/1475-2859-9-56 · 4.22 Impact Factor
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    • "Are the reported effects indeed mediated by ACS? First, we point out that the observed conversion cannot be a mere consequence of global derepression in the mutants. For example , the cdc6-1, cdc7-1, and ⌬sir2 mutations caused significant reduction in telomeric silencing (Ramachandran et al., 2006; Rehman et al., 2006) but did not alter the nature of ACS (Figure 2). Second, we can reasonably assume that the orc2-1 "
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    ABSTRACT: Subtelomeric genes are either fully active or completely repressed and can switch their state about once per 20 generations. This meta-stable telomeric position effect is mediated by strong repression signals emitted by the telomere and relayed/enhanced by weaker repressor elements called proto-silencers. In addition, subtelomeric regions contain sequences with chromatin partitioning and antisilencing activities referred to as subtelomeric antisilencing regions. Using extensive mutational analysis of subtelomeric elements, we show that ARS consensus sequence (ACS)-containing proto-silencers convert to antisilencers in several replication factor mutants. We point out the significance of the B1 auxiliary sequence next to ACS in mediating these effects. In contrast, an origin-derived ACS does not convert to antisilencer in mutants and its B1 element has little bearing on silencing. These results are specific for the analyzed ACS and in addition to the effects of each mutation (relative to wild type) on global silencing. Another line of experiments shows that Mcm5p possesses antisilencing activity and is recruited to telomeres in an ACS-dependent manner. Mcm5p persists at this location at the late stages of S phase. We propose that telomeric ACS are not static proto-silencers but conduct finely tuned silencing and antisilencing activities mediated by ACS-bound factors.
    Molecular biology of the cell 12/2008; 20(2):631-41. DOI:10.1091/mbc.E08-01-0099 · 4.47 Impact Factor
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    • "Others proposed that cell death induced by Htt aggregation mirrors the requirement of Htt for vesicular trafficking, a hypothesis that is reinforced by the recent discovery of a membrane targeting sequence at the very Nterminus and a palmitoylation site at cysteine 214 in Htt [15] [16]. An anti-apoptotic function has also been ascribed to Htt and apart from aggregation-induced indirect influences triggering oxidative stress and mitochondrial dysfunction, the protein may also exert a more direct effect since Htt with an expanded polyQ domain is unable to bind to HIP-1, a protein that contains a death box and can activate caspase-8 when released from Htt [17] [18] [19]. "
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    ABSTRACT: Budding yeast Saccharomyces cerevisiae has proven to be a valuable model organism for studying fundamental cellular processes across the eukaryotic kingdom including man. In this respect, complementation assays, in which the yeast protein is replaced by a homologous protein from another organism, have been very instructive. A newer trend is to use the yeast cell factory as a toolbox to understand cellular processes controlled by proteins for which the yeast lacks functional counterparts. An increasing number of studies have indicated that S. cerevisiae is a suitable model system to decipher molecular mechanisms involved in a variety of neurodegenerative disorders caused by aberrant protein folding. Here we review the current knowledge gained by the use of so-called humanized yeasts in the field of Huntington's, Parkinson's and Alzheimer's diseases.
    Biochimica et Biophysica Acta 08/2008; 1783(7):1381-95. DOI:10.1016/j.bbamcr.2008.01.020 · 4.66 Impact Factor
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