Regulation of sporulation in the yeast Saccharomyces cerevisiae.

Piekarska, Iga; Rytka, Joanna; Rempoła, Bożenna

doi:10.18388/abp.2010_2401

Cited by 19 publications

(22 citation statements)

References 1 publication

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“…Many significantly enriched GO terms were clustered into subsets of processes known to be regulated by Hst1 (and to a lesser extent Sir2) at the transcriptional level, and are expected to respond to NAM-induced inhibition of these sirtuins, e.g. sexual reproduction (sporulation) ( 62 , 63 ) and metabolism (‘de novo’ NAD biosynthetic process, sulfur amino acid, carboxylic acid, energy reserve metabolic processes) ( 17 , 18 ) (Table 3 ). GSEA also revealed that transcripts repressed in NAM-treated cells were significantly enriched in ribosome biogenesis, translation and tRNA modification (Supplementary Figure S1, Supplementary Table S4).…”

Section: Resultsmentioning

confidence: 99%

Chromosome-wide histone deacetylation by sirtuins prevents hyperactivation of DNA damage-induced signaling upon replicative stress

Simoneau¹,

Ricard²,

Weber³

et al. 2016

Nucleic Acids Res

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The Saccharomyces cerevisiae genome encodes five sirtuins (Sir2 and Hst1–4), which constitute a conserved family of NAD-dependent histone deacetylases. Cells lacking any individual sirtuin display mild growth and gene silencing defects. However, hst3Δ hst4Δ double mutants are exquisitely sensitive to genotoxins, and hst3Δ hst4Δ sir2Δ mutants are inviable. Our published data also indicate that pharmacological inhibition of sirtuins prevents growth of several fungal pathogens, although the biological basis is unclear. Here, we present genome-wide fitness assays conducted with nicotinamide (NAM), a pan-sirtuin inhibitor. Our data indicate that NAM treatment causes yeast to solicit specific DNA damage response pathways for survival, and that NAM-induced growth defects are mainly attributable to inhibition of Hst3 and Hst4 and consequent elevation of histone H3 lysine 56 acetylation (H3K56ac). Our results further reveal that in the presence of constitutive H3K56ac, the Slx4 scaffolding protein and PP4 phosphatase complex play essential roles in preventing hyperactivation of the DNA damage-response kinase Rad53 in response to spontaneous DNA damage caused by reactive oxygen species. Overall, our data support the concept that chromosome-wide histone deacetylation by sirtuins is critical to mitigate growth defects caused by endogenous genotoxins.

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Section: Resultsmentioning

confidence: 99%

Chromosome-wide histone deacetylation by sirtuins prevents hyperactivation of DNA damage-induced signaling upon replicative stress

Simoneau¹,

Ricard²,

Weber³

et al. 2016

Nucleic Acids Res

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“…To test whether the transcripts produced by T7 RNA polymerase were translated, we created diploid strains in which the only source of a1 messages was at HMR T7pro :: a1 . Sporulation requires a1 protein and can proceed with even small amounts present (reviewed in Piekarska et al 2010 ). Such strains were not able to sporulate (0 tetrads among thousands surveyed) in sporulation medium containing galactose and 10 mM nicotinamide to derepress HML and HMR .…”

Section: Resultsmentioning

confidence: 99%

On the Mechanism of Gene Silencing in Saccharomyces cerevisiae

Steakley

Rine

2015

G3 Genes|Genomes|Genetics

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Multiple mechanisms have been proposed for gene silencing in Saccharomyces cerevisiae, ranging from steric occlusion of DNA binding proteins from their recognition sequences in silenced chromatin to a specific block in the formation of the preinitiation complex to a block in transcriptional elongation. This study provided strong support for the steric occlusion mechanism by the discovery that RNA polymerase of bacteriophage T7 could be substantially blocked from transcribing from its cognate promoter when embedded in silenced chromatin. Moreover, unlike previous suggestions, we found no evidence for stalled RNA polymerase II within silenced chromatin. The effectiveness of the Sir protein–based silencing mechanism to block transcription activated by Gal4 at promoters in the domain of silenced chromatin was marginal, yet it improved when tested against mutant forms of the Gal4 protein, highlighting a role for specific activators in their sensitivity to gene silencing.

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“…A deficiency in glucose and nitrogen are known to induce meiosis followed G1 arrest of the mitotic cell cycle in diploid yeast cells 54 , 55 . When yeast cells starve for essential nutrients, sporulation and meiosis coupled with spore formation is induced 56 . However, absence of any nutritional deficiency in our experimental system indicates that G1 arrest and induction of meiosis are triggered by doxorubicin, which may cause a misperception in glucose sensing.…”

Section: Discussionmentioning

confidence: 99%

Doxorubicin induces an extensive transcriptional and metabolic rewiring in yeast cells

Taymaz-Nikerel

Karabekmez

Eraslan

et al. 2018

Sci Rep

125

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Doxorubicin is one of the most effective chemotherapy drugs used against solid tumors in the treatment of several cancer types. Two different mechanisms, (i) intercalation of doxorubicin into DNA and inhibition of topoisomerase II leading to changes in chromatin structure, (ii) generation of free radicals and oxidative damage to biomolecules, have been proposed to explain the mode of action of this drug in cancer cells. A genome-wide integrative systems biology approach used in the present study to investigate the long-term effect of doxorubicin in Saccharomyces cerevisiae cells indicated the up-regulation of genes involved in response to oxidative stress as well as in Rad53 checkpoint sensing and signaling pathway. Modular analysis of the active sub-network has also revealed the induction of the genes significantly associated with nucleosome assembly/disassembly and DNA repair in response to doxorubicin. Furthermore, an extensive re-wiring of the metabolism was observed. In addition to glycolysis, and sulfate assimilation, several pathways related to ribosome biogenesis/translation, amino acid biosynthesis, nucleotide biosynthesis, de novo IMP biosynthesis and one-carbon metabolism were significantly repressed. Pentose phosphate pathway, MAPK signaling pathway biological processes associated with meiosis and sporulation were found to be induced in response to long-term exposure to doxorubicin in yeast cells.

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Regulation of sporulation in the yeast Saccharomyces cerevisiae.

Cited by 19 publications

References 1 publication

Chromosome-wide histone deacetylation by sirtuins prevents hyperactivation of DNA damage-induced signaling upon replicative stress

Chromosome-wide histone deacetylation by sirtuins prevents hyperactivation of DNA damage-induced signaling upon replicative stress

On the Mechanism of Gene Silencing in Saccharomyces cerevisiae

Doxorubicin induces an extensive transcriptional and metabolic rewiring in yeast cells

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