Global genomic instability caused by reduced expression of DNA polymerase ε in yeast [DZP2-derived isolates]
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PROVIDER: PRJNA768823 | ENA |
REPOSITORIES: ENA
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Project description:Yeast Saccharomyces cerevisiae has been widely used as a model system for studying genome instability. Here, a heterozygous diploid S. cerevisiae strain DZP2 was generated to determine the genomic alterations induced by DNA polymerase ε. The expression of POL2 was regulated by the GAL1 promoter. In combination of a custom SNP microarray, the patterns of chromosomal instability induced by low Pol ε could be explored at a whole genome level in DZP2. Using this system, we found hundreds-fold higher rate of genomic alterations, including aneuploidy, loss of heterozygosity (LOH), and chromosomal rearrangement. DNA polymerase ε (Pol ε) is one of the three replicative eukaryotic DNA polymerases. Pol ε deficiency leads to genomic instability and multiple human diseases. Here, we explored global genomic alterations in yeast strains with reduced expression of POL2, the gene that encodes the catalytic subunit of Pol ε. Using whole-genome SNP microarray and sequencing, we found that low levels of Pol ε elevated the rates of mitotic recombination and chromosomal aneuploidy by two orders of magnitude. Strikingly, low levels of Pol ε resulted in a contraction of the number of repeats in the rDNA cluster and reduced the length of telomeres. These short telomeres led to an elevated frequency of break-induced replication, resulting in terminal loss of heterozygosity. In addition, low levels of Pol ε increased the rate of single-base mutations by 13-fold by a Pol ζ-dependent pathway. Finally, the patterns of genomic alterations caused by low levels of Pol ε were different from those observed in strains with low levels of the other replicative DNA polymerases Pol α and Pol δ, providing further insights into the different roles of the B-family DNA polymerases in maintaining genomic stability.
2021-10-07 | GSE185365 | GEO
Project description:Yeast Saccharomyces cerevisiae has been widely used as a model system for studying genome instability. Here, a heterozygous diploid S. cerevisiae strain DZP2 was generated to determine the genomic alterations induced by DNA polymerase ε. The expression of POL2 was regulated by the GAL1 promoter. In combination of a custom SNP microarray, the patterns of chromosomal instability induced by low Pol ε could be explored at a whole genome level in DZP2. Using this system, we found hundreds-fold higher rate of genomic alterations, including aneuploidy, loss of heterozygosity (LOH), and chromosomal rearrangement. DNA polymerase ε (Pol ε) is one of the three replicative eukaryotic DNA polymerases. Pol ε deficiency leads to genomic instability and multiple human diseases. Here, we explored global genomic alterations in yeast strains with reduced expression of POL2, the gene that encodes the catalytic subunit of Pol ε. Using whole-genome SNP microarray and sequencing, we found that low levels of Pol ε elevated the rates of mitotic recombination and chromosomal aneuploidy by two orders of magnitude. Strikingly, low levels of Pol ε resulted in a contraction of the number of repeats in the rDNA cluster and reduced the length of telomeres. These short telomeres led to an elevated frequency of break-induced replication, resulting in terminal loss of heterozygosity. In addition, low levels of Pol ε increased the rate of single-base mutations by 13-fold by a Pol ζ-dependent pathway. Finally, the patterns of genomic alterations caused by low levels of Pol ε were different from those observed in strains with low levels of the other replicative DNA polymerases Pol α and Pol δ, providing further insights into the different roles of the B-family DNA polymerases in maintaining genomic stability.
2021-10-07 | GSE185364 | GEO
Project description:Global genomic instability caused by reduced expression of DNA polymerase ε in yeast
| PRJNA768812 | ENA
Project description:Global genomic instability caused by reduced expression of DNA polymerase ε in yeast [DZP2-derived sectored colonies]
| PRJNA768822 | ENA
Project description:This SuperSeries is composed of the SubSeries listed below.
2021-10-07 | GSE185366 | GEO
Project description:The female reproductive tract (FRT) is vulnerable to sexually transmitted infections and therefore a well-tuned immune surveillance system is crucial for maintaining a healthy FRT. However, our understanding of the factors that impact viral infection of the FRT and the host response are not well understood. In this work, we investigate the role of a hormonally regulated type I interferon, IFN epsilon, in control of Zika virus (ZIKV) infection of the FRT. We demonstrate that IFN epsilon has anti-ZIKV properties using a combination of IFN epsilon KO mice, blockade of endogenous IFN epsilon by neutralising Abs and rescue of IFN epsilon KO mice by recombinant IFN epsilon administered directly to the FRT.
2023-02-14 | GSE223635 | GEO
Project description:Salmonella Typhimurium is one of the major foodborne pathogens due to its biofilm formation on food contact surfaces. A polymer of positively charged lysine, ε-Polylysine has been demonstrated to inhibit biofilm formation of both Gram-positive and -negative bacteria. To elucidate the mechanism for inhibition of biofilm formation by ε-Polylysine, transcriptional profiles were compared between the cells before and after treatment with ε-Polylysine in Salmonella Typhimurium. A genome-wide DNA microarray analysis was performed after cultivation in 0.1% bacto soytone in the presence of 0.001% ε-Polylysine at 30°C for 2 h. Genes involved in curli and cellulose production, quorum sensing, and flagellar motility were down-regulated, whereas genes associated with colanic acid synthesis were up-regulated. The data from microarray was validated by RT-qPCR. Furthermore, production of colanic acid in S. Typhimurium decreased in the presence of ε-Polylysine. The outcome of this study provides a basic understanding of the anti-biofilm mechanisms of ε-Polylysine and may contributes to develop new disinfectant to control biofilm during food manufacturing and storage.
2019-11-14 | GSE140300 | GEO
Project description:What is the impact of DNA pol epsilon deficiency on gene expression as well as on the expression of ncRNA, gene silencing? To further investigate the effects of DPB2 over-expression, the transcriptome of DPB2OE lines 1 and 3 was compared to that of wild-type plants by RNA sequencing. Plantlets were grown in vitro on half strength MS for 9 days and used for total RNA extraction. mRNA seq on wild-type Col-0, two DPB2 overexpression lines and one abo4-1 mutant knock out.
2016-07-22 | E-GEOD-71002 | biostudies-arrayexpress
Project description:This experiment is part of a larger study examining the anti-tumour properties of interferon epsilon in ovarian cancer. The objective of this experiment was to examine the direct activity of interferon epsilon on the mouse ovarian cancer cell line, ID8, and compare it to equivalent unit concentrations of interferon beta. The goal was to determine whether interferon epsilon and interferon beta induce different patterns of gene expression in ID8 cells.
2023-03-28 | GSE201345 | GEO
Project description:The multiple mutations comprising the epsilon variant demonstrates the independent convergent evolution of SARS-CoV-2 with its spike protein mutation L452R also present in the delta variant. Cells infected with live viral samples of the epsilon viral variant compared to non-epsilon variant displayed increased sensitivity to neutralization antibodies (NAb) suggesting an intact humoral response (P< 1.0 e-4). The ability for SARS-CoV2 to become more infectious but less virulent is supported mechanistically in the downregulation of viral processing pathways seen by multiomic analyses. Importantly, this paired transcriptomics and proteomic profiling of cellular response to live virus revealed an altered leukocyte response and metabolic mRNA processing in cells upon live viral infection of the epsilon variant. To ascertain host response to SARS-CoV-2 infection, primary COVID-19 positive nasopharyngeal samples were transcriptomically profiled a differential innate immune response (P<2.0 e-12) but, a relatively unaltered T cell response in the patients carrying the epsilon variant (P< 2.0 e-3). In fact, patients infected with SARS-CoV-2 and those vaccinated with the BNT162b2 vaccine have comparable CD4+/CD8+ T-cell immune responses to the B.1.429 variant (P<5 e-2). The epsilon variant alters viral processing response in infected cells, and the host innate immune response in COVID-19 positive nasopharyngeal swabs, but generates a protective host T cell response molecular signature in both vaccinated and unvaccinated patients.
2022-05-06 | PXD027995 | Pride