Shifts in rDNA levels act as a genome buffer promoting chromosome homeostasis

Deręgowska, Anna; Adamczyk, Jagoda; Kwiatkowska, Aleksandra; Gurgul, Artur; Skoneczny, Marek; Skoneczna, Adrianna; Szmatoła, Tomasz; Jasielczuk, Igor; Magda, Michal; Rawska, Ewa; Pabian, Sylwia; Panek, Anita D.; Kaplan, Jakub; Lewińska, Anna; Wnuk, Maciej

doi:10.1080/15384101.2015.1093705

Cited by 14 publications

(32 citation statements)

References 39 publications

(59 reference statements)

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“…Disparity mutagenesis is a promising tool for the creation of new types of eukaryotic mutants in various research fields and manufacturing industries. Additionally, the genomic analysis and GO enrichment analysis showed the relationship of the riboflavin production in MT strain with oxidative stress and the aging of cells, supporting the previous result that the accumulation of ROS and DNA damages appeared in other A.gossypii riboflavin-overproducing mutant [27].…”

Section: Discussionsupporting

confidence: 83%

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Genomic analysis of a riboflavin-overproducing Ashbya gossypii mutant isolated by disparity mutagenesis

Kato

Azegami

Yokomori

et al. 2020

Preprint

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Background: Ashbya gossypii naturally overproduces riboflavin and has been utilized for industrial riboflavin production. To improve riboflavin production, various approaches have been developed. In this study, to investigate the change in metabolism of a riboflavin-overproducing mutant, namely, the W122032 strain (MT strain) that was isolated by disparity mutagenesis, genomic analysis was carried out. Results: In the genomic analysis, 33 homozygous and 1377 heterozygous mutations in the coding sequences of the genome of MT strain were detected. Among these heterozygous mutations, the proportion of mutated reads in each gene was different, ranging from 21 to 75%. These results suggest that the MT strain may contain multiple nuclei containing different mutations. We tried to isolate haploid spores from the MT strain to prove its ploidy, but this strain did not sporulate under the conditions tested. Heterozygous mutations detected in genes which are important for sporulation likely contribute to the sporulation deficiency of the MT strain. Homozygous and heterozygous mutations were found in genes encoding enzymes involved in amino acid metabolism, the TCA cycle, purine and pyrimidine nucleotide metabolism and the DNA mismatch repair system. One homozygous mutation in AgILV2 gene encoding acetohydroxyacid synthase, which is also a flavoprotein in mitochondria, was found. Gene ontology (GO) enrichment analysis showed heterozygous mutations in all 22 DNA helicase genes and genes involved in oxidation-reduction process. Conclusion: This study suggests that oxidative stress and the aging of cells were involved in the riboflavin over-production in A. gossypii riboflavin over-producing mutant and provides new insights into riboflavin production in A. gossypii and the usefulness of disparity mutagenesis for the creation of new types of mutants for metabolic engineering.

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Section: Discussionsupporting

confidence: 83%

“…In yeasts, the number of rRNA gene repeats is normally maintained for genome stability and determination of life span [25,26]. Moreover, the rRNA gene controls chromosome homeostasis [27]. When the number of rRNA gene repeats increases, rRNA gene instability and aging phenotypes are observed.…”

Section: Genome Analysis Of Each Strain and Identification Of Mutatiomentioning

confidence: 99%

Genomic analysis of a riboflavin-overproducing Ashbya gossypii mutant isolated by disparity mutagenesis

Kato

Azegami

Yokomori

et al. 2020

Preprint

View full text Add to dashboard Cite

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“…Nop1 (ortholog of mammalian fibrillarin) and Nop2 (ortholog of mammalian p120), involved in pre-rRNA processing and ribosome biogenesis [ 67 , 68 ], are histone glutamine methyltransferase that modifies H2A at Q105 and rRNA m5C methyltransferase that methylates cytosine at position 2870 of 25S rRNA, respectively [ 69 , 70 ]. The effects of Nop1 and Nop2 proteins on nucleolus fragmentation have been documented [ 71 – 73 ]. Overexpression of NOP2 gene resulted in nucleolus fragmentation [ 71 ].…”

Section: Discussionmentioning

confidence: 99%

Adaptive response to chronic mild ethanol stress involves ROS, sirtuins and changes in chromosome dosage in wine yeasts

et al. 2016

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Industrial yeast strains of economic importance used in winemaking and beer production are genomically diverse and subjected to harsh environmental conditions during fermentation. In the present study, we investigated wine yeast adaptation to chronic mild alcohol stress when cells were cultured for 100 generations in the presence of non-cytotoxic ethanol concentration. Ethanol-induced reactive oxygen species (ROS) and superoxide signals promoted growth rate during passages that was accompanied by increased expression of sirtuin proteins, Sir1, Sir2 and Sir3, and DNA-binding transcription regulator Rap1. Genome-wide array-CGH analysis revealed that yeast genome was shaped during passages. The gains of chromosomes I, III and VI and significant changes in the gene copy number in nine functional gene categories involved in metabolic processes and stress responses were observed. Ethanol-mediated gains of YRF1 and CUP1 genes were the most accented. Ethanol also induced nucleolus fragmentation that confirms that nucleolus is a stress sensor in yeasts. Taken together, we postulate that wine yeasts of different origin may adapt to mild alcohol stress by shifts in intracellular redox state promoting growth capacity, upregulation of key regulators of longevity, namely sirtuins and changes in the dosage of genes involved in the telomere maintenance and ion detoxification.

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“…In yeasts, the number of rRNA gene repeats is normally maintained for genome stability and determination of life span [20,21]. Moreover, the rRNA gene controls chromosome homeostasis [22]. When the number of rRNA gene repeats increases, rRNA gene instability and aging phenotypes are observed.…”

Section: Resultsmentioning

confidence: 99%

Genomic analysis of a riboflavin-overproducing Ashbya gossypii mutant isolated by disparity mutagenesis

et al. 2020

View full text Add to dashboard Cite

Background: Ashbya gossypii naturally overproduces riboflavin and has been utilized for industrial riboflavin production. To improve riboflavin production, various approaches have been developed. In this study, to investigate the change in metabolism of a riboflavin-overproducing mutant, namely, the W122032 strain (MT strain) that was isolated by disparity mutagenesis, genomic analysis was carried out. Results: In the genomic analysis, 33 homozygous and 1377 heterozygous mutations in the coding sequences of the genome of MT strain were detected. Among these heterozygous mutations, the proportion of mutated reads in each gene was different, ranging from 21 to 75%. These results suggest that the MT strain may contain multiple nuclei containing different mutations. We tried to isolate haploid spores from the MT strain to prove its ploidy, but this strain did not sporulate under the conditions tested. Heterozygous mutations detected in genes which are important for sporulation likely contribute to the sporulation deficiency of the MT strain. Homozygous and heterozygous mutations were found in genes encoding enzymes involved in amino acid metabolism, the TCA cycle, purine and pyrimidine nucleotide metabolism and the DNA mismatch repair system. One homozygous mutation in AgILV2 gene encoding acetohydroxyacid synthase, which is also a flavoprotein in mitochondria, was found. Gene ontology (GO) enrichment analysis showed heterozygous mutations in all 22 DNA helicase genes and genes involved in oxidation-reduction process. Conclusion: This study suggests that oxidative stress and the aging of cells were involved in the riboflavin overproduction in A. gossypii riboflavin over-producing mutant and provides new insights into riboflavin production in A. gossypii and the usefulness of disparity mutagenesis for the creation of new types of mutants for metabolic engineering.

show abstract

Shifts in rDNA levels act as a genome buffer promoting chromosome homeostasis

Cited by 14 publications

References 39 publications

Genomic analysis of a riboflavin-overproducing Ashbya gossypii mutant isolated by disparity mutagenesis

Genomic analysis of a riboflavin-overproducing Ashbya gossypii mutant isolated by disparity mutagenesis

Adaptive response to chronic mild ethanol stress involves ROS, sirtuins and changes in chromosome dosage in wine yeasts

Genomic analysis of a riboflavin-overproducing Ashbya gossypii mutant isolated by disparity mutagenesis

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