scholarly journals Replicative aging is associated with loss of genetic heterogeneity from extrachromosomal circular DNA in Saccharomyces cerevisiae

2020 ◽  
Vol 48 (14) ◽  
pp. 7883-7898 ◽  
Author(s):  
Iñigo Prada-Luengo ◽  
Henrik D Møller ◽  
Rasmus A Henriksen ◽  
Qian Gao ◽  
Camilla Eggert Larsen ◽  
...  
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Genetic Variation ◽  
Ribosomal Dna ◽  
Replicative Aging ◽  
Circular Dna ◽  
Circular Dnas ◽  
Low Glucose ◽  
Chromosomal Amplifications ◽  
Mother Cells ◽  
Massive Accumulation

Abstract Circular DNA can arise from all parts of eukaryotic chromosomes. In yeast, circular ribosomal DNA (rDNA) accumulates dramatically as cells age, however little is known about the accumulation of other chromosome-derived circles or the contribution of such circles to genetic variation in aged cells. We profiled circular DNA in Saccharomyces cerevisiae populations sampled when young and after extensive aging. Young cells possessed highly diverse circular DNA populations but 94% of the circular DNA were lost after ∼15 divisions, whereas rDNA circles underwent massive accumulation to >95% of circular DNA. Circles present in both young and old cells were characterized by replication origins including circles from unique regions of the genome and repetitive regions: rDNA and telomeric Y’ regions. We further observed that circles can have flexible inheritance patterns: [HXT6/7circle] normally segregates to mother cells but in low glucose is present in up to 50% of cells, the majority of which must have inherited this circle from their mother. Interestingly, [HXT6/7circle] cells are eventually replaced by cells carrying stable chromosomal HXT6 HXT6/7 HXT7 amplifications, suggesting circular DNAs are intermediates in chromosomal amplifications. In conclusion, the heterogeneity of circular DNA offers flexibility in adaptation, but this heterogeneity is remarkably diminished with age.

scholarly journals Replicative aging is associated with loss of genetic heterogeneity from extrachromosomal circular DNA in Saccharomyces cerevisiae

2020 ◽  
Author(s):  
Iñigo Prada-Luengo ◽  
Henrik D. Møller ◽  
Rasmus A. Henriksen ◽  
Qian Gao ◽  
Camilla E. Larsen ◽  
...  
Keyword(s):  
Genetic Heterogeneity ◽  
Glucose Transporter ◽  
Transporter Gene ◽  
Replicative Aging ◽  
Circular Dna ◽  
Chromosomal Origin ◽  
Adaptive Solution ◽  
Chromosomal Amplifications ◽  
Massive Accumulation ◽  
Eukaryotic Genomes

Circular DNA of chromosomal origin form from all parts of eukaryotic genomes. In yeast, circular rDNA accumulates as cells divide, contributing to replicative aging. However, little is known about how other chromosome-deri ved circles segregate and contribute to geneticvariation as cells age. We identified circular DNA across the genome of young S. cerevisiae populations and their aged descendants. Young cells had highly diverse circular DNA populations, but lost 94% of the different circular DNA after 20 divisions. Circles present in both young and old cells were characterized by replication origins and included circles from unique regions of the genome, rDNA circles and telomeric Y’ circles. The loss in genetic heterogeneity in aged cells was accompanied by massive accumulation of rDNA circles >95% of all circular DNA. We discovered circles had flexible inherence patterns. Glucose limited conditions selected for cells with glucose-transporter gene circles, [HXT6/7circle], and up to 50% of cells in a population carried them. [HXT6/7circle] cells were eventually substituted by cells carrying stable chromosomal HXT6 HXT6/7 HXT7 amplifications, suggesting circular DNA were intermediates in chromosomal amplifications. In conclusion, DNA circles can offer a flexible adaptive solution but cells lose genetic heterogeneity from circular DNA as they undergo replicative aging.

scholarly journals Mitochondrial genetics, circular DNA and the mechanism of thepetitemutation in yeast

1974 ◽  
Vol 24 (1) ◽  
pp. 43-57 ◽  
Author(s):  
G. D. Clark-Walker ◽  
George L. Gabor Miklos
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Structural Rearrangements ◽  
Dna Molecules ◽  
Mitochondrial Genetics ◽  
General Hypothesis ◽  
Mitochondrial Recombination ◽  
Circular Dna ◽  
Bacterial Plasmids ◽  
Circular Dnas

SUMMARYWe propose a general hypothesis involving properties of circular DNA which can explain such phenomena as thepetitemutation, suppressiveness, and the polarity observed in mitochondrial recombination in the yeastSaccharomyces cerevisiae. This hypothesis involves excision and insertion events between circular DNA molecules as well as structural rearrangements in the DNA generated by these events. The special properties of circular DNA have been considered in analysing recombination, and a number of results are obtained which are not intuitively apparent.This hypothesis can be applied to any situation involving circular DNA such as bacterial plasmids and cytoplasmic circular DNAs, where the opportunity exists for recombination and rearrangement events.

scholarly journals Extrachromosomal circular DNA is common in yeast

2015 ◽  
Vol 112 (24) ◽  
pp. E3114-E3122 ◽  
Author(s):  
Henrik D. Møller ◽  
Lance Parsons ◽  
Tue S. Jørgensen ◽  
David Botstein ◽  
Birgitte Regenberg
Keyword(s):  
Genetic Variation ◽  
Repetitive Sequences ◽  
Ribosomal Genes ◽  
Purification Method ◽  
Circular Dna ◽  
Consensus Sequences ◽  
Highly Sensitive ◽  
Circular Dnas ◽  
Genomic Regions ◽  
Genome Scale

Examples of extrachromosomal circular DNAs (eccDNAs) are found in many organisms, but their impact on genetic variation at the genome scale has not been investigated. We mapped 1,756 eccDNAs in the Saccharomyces cerevisiae genome using Circle-Seq, a highly sensitive eccDNA purification method. Yeast eccDNAs ranged from an arbitrary lower limit of 1 kb up to 38 kb and covered 23% of the genome, representing thousands of genes. EccDNA arose both from genomic regions with repetitive sequences ≥15 bases long and from regions with short or no repetitive sequences. Some eccDNAs were identified in several yeast populations. These eccDNAs contained ribosomal genes, transposon remnants, and tandemly repeated genes (HXT6/7, ENA1/2/5, and CUP1-1/-2) that were generally enriched on eccDNAs. EccDNAs seemed to be replicated and 80% contained consensus sequences for autonomous replication origins that could explain their maintenance. Our data suggest that eccDNAs are common in S. cerevisiae, where they might contribute substantially to genetic variation and evolution.

scholarly journals A Role for the Actin Cytoskeleton of Saccharomyces cerevisiae in Bipolar Bud-Site Selection

1997 ◽  
Vol 136 (1) ◽  
pp. 111-123 ◽  
Author(s):  
Shirley Yang ◽  
Kathryn R. Ayscough ◽  
David G. Drubin
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Actin Cytoskeleton ◽  
Site Selection ◽  
Mitotic Checkpoint ◽  
Cell Cortex ◽  
Spatial Cues ◽  
Genes Encoding ◽  
Mother And Daughter ◽  
Mother Cells ◽  
Bud Site

Saccharomyces cerevisiae cells select bud sites according to one of two predetermined patterns. MATa and MATα cells bud in an axial pattern, and MATa/α cells bud in a bipolar pattern. These budding patterns are thought to depend on the placement of spatial cues at specific sites in the cell cortex. Because cytoskeletal elements play a role in organizing the cytoplasm and establishing distinct plasma membrane domains, they are well suited for positioning bud-site selection cues. Indeed, the septin-containing neck filaments are crucial for establishing the axial budding pattern characteristic of MATa and MATα cells. In this study, we determined the budding patterns of cells carrying mutations in the actin gene or in genes encoding actin-associated proteins: MATa/α cells were defective in the bipolar budding pattern, but MATa and MATα cells still exhibit a normal axial budding pattern. We also observed that MATa/α actin cytoskeleton mutant daughter cells correctly position their first bud at the distal pole of the cell, but mother cells position their buds randomly. The actin cytoskeleton therefore functions in generation of the bipolar budding pattern and is required specifically for proper selection of bud sites in mother MATa/α cells. These observations and the results of double mutant studies support the conclusion that different rules govern bud-site selection in mother and daughter MATa/α cells. A defective bipolar budding pattern did not preclude an sla2-6 mutant from undergoing pseudohyphal growth, highlighting the central role of daughter cell bud-site selection cues in the formation of pseudohyphae. Finally, by examining the budding patterns of mad2-1 mitotic checkpoint mutants treated with benomyl to depolymerize their microtubules, we confirmed and extended previous evidence indicating that microtubules do not function in axial or bipolar bud-site selection.

scholarly journals Actualización en caracterización molecular de levaduras de interés industrial

2016 ◽  
Vol 18 (2) ◽  
pp. 129 ◽  
Author(s):  
Jorge Alberto Vásquez C ◽  
Mauricio Ramirez Castrillón ◽  
Zulma Isabel Monsalve F
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Ribosomal Dna

Las levaduras, además de ser un modelo de la investigación biomédica, tienen diversas aplicaciones en la industria alimentaria, en agricultura y la producción de etanol combustible. Dado que la calidad y la cantidad del producto dependen de la dinámica y la frecuencia de los microorganismos presentes en la fermentación, el uso de herramientas de caracterización molecular se ha incrementado y popularizado en las industrias que emplean levaduras. Estas técnicas se basan en la amplificación o análisis por enzimas de restricción de una porción del ADN genómico de levadura y se clasifican de acuerdo a su capacidad de resolución taxonómica para discriminar a nivel inter o intra-específica. La primera parte de la revisión incluye pruebas interespecíficas tales como, análisis de restricción o RFLP para las regiones ITS2, ITS1-5.8, D1 / D2 de los genes 26S ribosomal DNA. La segunda parte incluye, pruebas de uso común para caracterización nivel de cepa, tales como: la amplificación aleatoria del ADN polimórfico (RAPD), análisis cromosómico por electroforesis en gel de campo pulsado (PFGE), análisis de restricción del ADN mitocondrial (ADNmt- RFLP) análisis por mini / micro satélites y la huella genética de ADN por amplificación de regiones interdelta de los transposones Ty. Esta revisión describe y discute los detalles técnicos de los métodos más utilizados para la caracterización molecular de las levaduras y algunos ejemplos de sus aplicaciones en el contexto industrial.Palabras clave: Levaduras, caracterización molecular, identificación intraespecífica especies, Saccharomyces cerevisiae.

scholarly journals Loss of Ubp3 increases silencing, decreases unequal recombination in rDNA, and shortens the replicative life span in Saccharomyces cerevisiae

2014 ◽  
Vol 25 (12) ◽  
pp. 1916-1924 ◽  
Author(s):  
David Öling ◽  
Rehan Masoom ◽  
Kristian Kvint
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Rna Polymerase ◽  
Life Span ◽  
Rna Polymerase Ii ◽  
Ribosomal Dna ◽  
Genetic Evidence ◽  
Wild Type ◽  
Replicative Life Span ◽  
Unequal Recombination

Ubp3 is a conserved ubiquitin protease that acts as an antisilencing factor in MAT and telomeric regions. Here we show that ubp3∆ mutants also display increased silencing in ribosomal DNA (rDNA). Consistent with this, RNA polymerase II occupancy is lower in cells lacking Ubp3 than in wild-type cells in all heterochromatic regions. Moreover, in a ubp3∆ mutant, unequal recombination in rDNA is highly suppressed. We present genetic evidence that this effect on rDNA recombination, but not silencing, is entirely dependent on the silencing factor Sir2. Further, ubp3∆ sir2∆ mutants age prematurely at the same rate as sir2∆ mutants. Thus our data suggest that recombination negatively influences replicative life span more so than silencing. However, in ubp3∆ mutants, recombination is not a prerequisite for aging, since cells lacking Ubp3 have a shorter life span than isogenic wild-type cells. We discuss the data in view of different models on how silencing and unequal recombination affect replicative life span and the role of Ubp3 in these processes.

scholarly journals The Swi/Snf Chromatin Remodeling Complex Is Required for Ribosomal DNA and Telomeric Silencing in Saccharomyces cerevisiae

2004 ◽  
Vol 24 (18) ◽  
pp. 8227-8235 ◽  
Author(s):  
Vardit Dror ◽  
Fred Winston
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Rna Polymerase ◽  
Rna Polymerase Ii ◽  
Chromatin Remodeling ◽  
Ribosomal Dna ◽  
Transcriptional Activation ◽  
Rdna Locus ◽  
Detectable Effect ◽  
Chromatin Remodeling Complex ◽  
Two Factors

ABSTRACT The Swi/Snf chromatin remodeling complex has been previously demonstrated to be required for transcriptional activation and repression of a subset of genes in Saccharomyces cerevisiae. In this work we demonstrate that Swi/Snf is also required for repression of RNA polymerase II-dependent transcription in the ribosomal DNA (rDNA) locus (rDNA silencing). This repression appears to be independent of both Sir2 and Set1, two factors known to be required for rDNA silencing. In contrast to many other rDNA silencing mutants that have elevated levels of rDNA recombination, snf2Δ mutants have a significantly decreased level of rDNA recombination. Additional studies have demonstrated that Swi/Snf is also required for silencing of genes near telomeres while having no detectable effect on silencing of HML or HMR.

scholarly journals Daughter cells of Saccharomyces cerevisiae from old mothers display a reduced life span.

1994 ◽  
Vol 127 (6) ◽  
pp. 1985-1993 ◽  
Author(s):  
B K Kennedy ◽  
N R Austriaco ◽  
L Guarente
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Life Span ◽  
Daughter Cell ◽  
Young Mothers ◽  
Young Mother ◽  
Yeast Saccharomyces Cerevisiae ◽  
Daughter Cells ◽  
Per Se ◽  
Mother Cells ◽  
Maximum Occurrence

The yeast Saccharomyces cerevisiae typically divides asymmetrically to give a large mother cell and a smaller daughter cell. As mother cells become old, they enlarge and produce daughter cells that are larger than daughters derived from young mother cells. We found that occasional daughter cells were indistinguishable in size from their mothers, giving rise to a symmetric division. The frequency of symmetric divisions became greater as mother cells aged and reached a maximum occurrence of 30% in mothers undergoing their last cell division. Symmetric divisions occurred similarly in rad9 and ste12 mutants. Strikingly, daughters from old mothers, whether they arose from symmetric divisions or not, displayed reduced life spans relative to daughters from young mothers. Because daughters from old mothers were larger than daughters from young mothers, we investigated whether an increased size per se shortened life span and found that it did not. These findings are consistent with a model for aging that invokes a senescence substance which accumulates in old mother cells and is inherited by their daughters.

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