Replicative age induces mitotic recombination in the ribosomal RNA gene cluster of Saccharomyces cerevisiae.

paper Cited Public

Authors: Lindstrom, Derek L; Leverich, Christina K; Henderson, Kiersten A; Gottschling, Daniel E
Year: 2011
Journal: PLoS genetics
PMID: 21436897
DOI: 10.1371/journal.pgen.1002015
PMCID: PMC3060066

Figure 1

Age-associated LOH events are a result of recombination within the rDNA array.A) Right y-axis: LOH rates at MET15 (open boxes) reported as total LOH events per cell division. Error bars indicate Standard Error of the Mean (SEM). Left y-axis: Percent viability of mother cells in the aging culture (grey line). B) Right y-axis: LOH rates at Chromosome IV (black line) reported as total LOH events per cell division. Error bars indicate SEM. Left y-axis: Percent viability of mother cells in the aging culture (closed circles). C) A schematic of marker placement on Chromosome XII used to determine homologous recombination break points. D) Table indicating the relative sizes of intervals between markers and the proportion of LOH events that originate within each interval.

LLM interpretation

This figure consists of two line graphs, a genetic schematic, and a data table analyzing loss of heterozygosity (LOH) during aging. Panels A and B show that as the percent viability of mother cells decreases over 100 hours, the LOH rate increases on Chromosome XII (open boxes) and remains relatively low/stable on Chromosome IV (black line). Panel C provides a schematic of marker placement on Chromosome XII, and Panel D is a table showing that the majority of LOH events (74% of intervals and 90% of crossovers) originate within the rDNA array.

Figure 2

LOH rates at MET15 in aging cells present a constant ratio of reciprocal/non-reciprocal events.A diagram of UCC5185 colony color markers located on Chromosome XII, with expected results of reciprocal and non-reciprocal LOH events. Non-reciprocal events can also lead to black/white half-sectored colonies. (Note: The normal chromosomal copies of ADE2 have been deleted.) B) LOH rates for UCC5185 at MET15 reported as total LOH events per cell division. Error bars indicate SEM. The sample size at each time point ranges from 21 to 28. LOH rates are significantly increased at 45, 70 and 95 hours, (unpaired t-test; P values are 0.0003, <0.0001, and <0.0001 respectively). C) LOH events from panel B segregated into reciprocal and non-reciprocal LOH rates. Error bars indicate SEM.

LLM interpretation

This figure consists of a diagram (A) and two line graphs (B and C) illustrating loss of heterozygosity (LOH) rates at the MET15 locus over time. Panel A diagrams the genetic mechanisms and resulting colony colors for reciprocal and non-reciprocal LOH events. Panels B and C show that total LOH rates and the rates of both reciprocal and non-reciprocal events increase over 95 hours, with total LOH rates significantly higher at 45, 70, and 95 hours (p < 0.001).

Figure 3

Age-associated LOH events depend on FOB1.Total LOH rates at MET15 from individual aging cultures of UCC526 (fob1Δ). Error bars indicate SEM.

LLM interpretation

This line graph compares the loss of heterozygosity (LOH) rate per $10^3$ divisions over 95 hours between wild-type and $fob1\Delta$ yeast cultures. The wild-type group shows a steady increase in LOH rate over time, reaching approximately 16 by 95 hours, while the $fob1\Delta$ group remains relatively flat and significantly lower, staying below 2. The x-axis represents time in hours and the y-axis represents the LOH rate, with error bars indicating the standard error of the mean (SEM).

Figure 4

An inducible allele of FOB1 reveals the accumulation of aging factors in the absence of Fob1.Total MET15 LOH rates in aging UCC8912 cells exposed to no doxycycline (FOB1 On; filled squares) or 20 µg/mL doxycycline (FOB1 Off; open squares). At 65 hours, a portion of the Fob1 Off culture was harvested and transferred to media with no doxycycline (FOB1 Off → On; triangles).

LLM interpretation

This line graph shows the total *MET15* loss of heterozygosity (LOH) rate per $10^3$ divisions over 70 hours for three conditions: *TET-FOB1* On (filled squares), *TET-FOB1* Off (open squares), and *TET-FOB1* Off $\rightarrow$ On (triangles). The *TET-FOB1* On group shows a steady increase in LOH rates over time, reaching approximately 20 by 70 hours, while the *TET-FOB1* Off group remains consistently low (below 5). Upon switching from Off to On at 65 hours, the LOH rate in the *TET-FOB1* Off $\rightarrow$ On group increases sharply to match the *TET-FOB1* On level by 70 hours.

Figure 5

Double mutant analysis of fob1 and cohibin mutants.Scatter plots of total LOH rates at the MET15 locus in young cells with genotypes as indicated.

LLM interpretation

This figure is a scatter plot showing the total loss of heterozygosity (LOH) rates per $10^3$ divisions at the MET15 locus in young cells across five genotypes. The y-axis represents the LOH rate, while the x-axis lists the genotypes: Wild Type, *lrs4*, *lrs4 fob1*, *csm1*, and *csm1 fob1*. The *lrs4* and *lrs4 fob1* mutants exhibit the highest LOH rates, while the Wild Type shows the lowest, and *csm1* mutants show intermediate rates.

Figure 6

Declining Sir2 levels do not correlate with the onset of age-associated LOH events.A) Western blotting against Sir2 and Vma2 in total protein extracts prepared from cells aged for hours as indicated at top. Sir2 levels were normalized to Vma2 and quantified by densitometry, with wild type Sir2 levels in log cultures set to 1x Fold. Mean bud scar counts at 26 hours: WT = 15.5, SIR2OE = 18.0. B) Total LOH rates at MET15 of wild type UCC5185 (filled squares) compared to the SIR2OE strain UCC8910 (open squares). Error bars indicate SEM. C) Western blotting against Sir2 and Vma2 in total protein extracts prepared from aged cells. Genotype and hours of aging indicated at top. Mean bud scar counts at 26 hours: sas2Δ = 16.8, fob1Δ = 15.7.

LLM interpretation

This figure consists of two Western blots (A, C) and a line graph (B). Panel A shows a decline in Sir2 protein levels over time (2 to 50 hours) in both wild type and *SIR2OE* strains, while Panel C shows similar Sir2 declines in *sas2Δ* and *fob1Δ* strains, with Vma2 used as a loading control. Panel B displays the LOH rate per $10^3$ divisions over 95 hours, showing a similar upward trend for both wild type (filled squares) and *SIR2OE* (open squares) strains.

Figure 7

Characterization of LOH events in young sir2Δ cells.A) Scatter plots of total LOH rates at the MET15 locus in young cells with genotypes as indicated. B) Rates of total LOH events at MET15 in young cells for wild type (UCC5185) and sir2Δ (UCC8836) strains. Rates of reciprocal/non-reciprocal events were significantly different in the sir2Δ strain but not in wild type (Fisher's exact test by contingency tables, p values indicated above columns). C) Rates of total LOH events at MET15 in replicatively aging sir2Δ cultures. Right y-axis: LOH rates at MET15 (open boxes) reported as total LOH events per cell division. Error bars indicate SEM. Left y-axis: Percent viability of mother cells in the aging culture (grey line).

LLM interpretation

This figure consists of three panels characterizing loss of heterozygosity (LOH) rates at the *MET15* locus. Panel A uses scatter plots to show that LOH rates are significantly higher in *sir2Δ* cells compared to wild type and *sir2Δ fob1Δ* cells. Panel B uses a bar chart to show that *sir2Δ* cells have higher rates of both reciprocal (R) and non-reciprocal (NR) LOH events compared to wild type, with a significant difference between R and NR events in the *sir2Δ* strain (p < 0.0001). Panel C displays a line graph showing that as the percent viability of aging *sir2Δ* mother cells decreases over 80 hours, the LOH rate per $10^3$ divisions increases.

Figure 8

ERC accumulation in aging diploid cells.A) Southern blot of total genomic DNA isolated from aging populations and digested with BamHI and RecBCD. Genotypes and replicative age in hours indicated at top. ERC species indicated at right: ERC Concatamers- Con.; Dimers- Di.; Monomers- Mono. Mean bud scar counts at 26 hours: WT = 15.3 fob1Δ = 15.6, bud6Δ = 12.9. Lower panel: Southern blot of total genomic DNA isolated from aging cell populations, digested with BamHI and probed for NPR2. B) ERC levels normalized to NPR2 (panel A). For individual ERC species, wild type 5-hour lanes are set as 1x fold. Total ERCs were calculated as the sum of the integrated density of each ERC species, with the wild type 5-hour lane set as 1x fold. C) Total LOH rates at MET15 in aging cultures of the bud6Δ strain UCC8904. Error bars indicate SEM.

LLM interpretation

This figure consists of Southern blots (A), bar charts (B), and a line graph (C) analyzing ERC accumulation and LOH rates in aging yeast cells. Panel A shows DNA bands for ERC species (concatamers, dimers, monomers) and the NPR2 loading control across Wild Type, *fob1Δ*, and *bud6Δ* strains at 5, 26, and 50 hours. Panel B quantifies these species, showing that total ERCs and specific forms (like dimers) generally increase with age, with variations between genotypes. Panel C displays a line graph showing that the LOH rate per $10^3$ divisions in the *bud6Δ* strain increases steadily from 0 to 95 hours.

#	Section	Preview
20	Results — Disruption of cohesion increases LOH rates independent of Fob1	One mechanism by which LOH could increase in old cells is through an age-associated defect in sister…
21	Results — Disruption of cohesion increases LOH rates independent of Fob1	The effect of disrupting sister chromatid cohesion was examined by deleting the genes encoding the…
22	Results — A decline in Sir2 protein levels in aging cells does not correlate with increased LOH rates	The protein deacetylase Sir2 has been implicated in the yeast aging process and life span…
23	Results — A decline in Sir2 protein levels in aging cells does not correlate with increased LOH rates	It was recently shown that Sir2 protein levels decline in aging haploid cells [36]. To determine if…
24	Results — A decline in Sir2 protein levels in aging cells does not correlate with increased LOH rates	fallen 10-fold by 26 hours, and were further reduced by 50 hours. This same decline was also…
25	Results — Modulation of Sir2 protein levels in aging cells does not affect age-associated LOH	The observation that Sir2 protein levels decline precipitously 20 hours before rDNA recombination…
26	Results — Modulation of Sir2 protein levels in aging cells does not affect age-associated LOH	Next, we examined LOH rates at MET15 in the SIR2OE strain to determine if increased Sir2 levels…
27	Results — Modulation of Sir2 protein levels in aging cells does not affect age-associated LOH	To confirm this result, we attempted to stabilize Sir2 protein levels by a second method. In a…
28	Results — Modulation of Sir2 protein levels in aging cells does not affect age-associated LOH	Following the same logic behind our examination of cohesion, we characterized the pattern of LOH…
29	Results — Modulation of Sir2 protein levels in aging cells does not affect age-associated LOH	Lastly, we examined LOH rates in aging sir2Δ cells to determine if there is an age-associated…
30	Results — ERCs accumulate to high levels in fob1Δ cells	Intrachromosomal recombination between the rDNA repeats can produce extrachromosomal rDNA circles…
31	Results — ERCs accumulate to high levels in fob1Δ cells	In order to examine this issue, we found it necessary to further develop methods employed to examine…
32	Results — ERCs accumulate to high levels in fob1Δ cells	First, we compared ERC levels in wild type and fob1Δ cells. A modest increase in all three species…
33	Results — ERCs accumulate to high levels in fob1Δ cells	levels in fob1Δ cells were still ∼50% lower than wild type cells after aging replicatively for 50…
34	Results — Age-associated LOH is not suppressed by reduced ERC accumulation	While the fob1Δ strain permitted us to determine the utility of our ERC measurements with age, it…
35	Discussion — Age-associated genomic instability in respiration-competent cells	Previously we discovered an age-associated, genome-wide increase in LOH in yeast that results from…
36	Discussion — Age-associated genomic instability in respiration-competent cells	Using the MEP, we have discovered a distinct age-associated LOH phenotype in cells that retain…
37	Discussion — Age-associated genomic instability in respiration-competent cells	We observed a significant increase in both reciprocal and non-reciprocal recombination events, which…
38	Discussion — Loss of cohesion or Sir2 protein does not appear to lead to increased age-associated LOH rates	Taking advantage of the requirement for Fob1, we investigated potential mechanisms leading to the…
39	Discussion — Using the MEP for biochemical analysis of populations at their median RLS	Aging is typically accompanied by an exponentially increasing hazard rate of death – i.e. the…

Name	Type
35S rRNA local	drug
ADE2 local	gene
adenine local	drug
ADH1A	gene
aerobic glycolysis local	phenotype
age	phenotype
Age-associated genomic instability local	phenotype
age-associated increase in LOH local	phenotype
age-associated increase in mitotic recombination local	phenotype
age-associated LOH phenotype local	phenotype
Age-associated LOH phenotype local	phenotype
age-associated loss of heterozygosity local	phenotype
Age-associated loss of heterozygosity local	phenotype
aged mother cells local	cohort
aging	phenotype
aging cells local	cohort
aging mothers local	phenotype
ampicillin local	drug
average population local	cohort
BamHI	drug
BCA protein assay local	drug
black colony sector local	phenotype
BUD6 local	gene
bud6Δ local	variant
bud scars local	phenotype
calcofluor white local	drug
cancer	phenotype
cancer development	phenotype
cell cycle arrest	phenotype
cellular senescence	phenotype
colony color phenotype local	phenotype
common lab strain of Saccharomyces cerevisiae local	cohort
crisis state local	phenotype
CSM1 local	gene
csm1Δ local	variant
CUP1 local	gene
diploid cells local	cohort
diploid cells local	phenotype
DNA2 local	gene
DNA damage	phenotype
DNA polymerase α local	gene
DNA polymerase δ local	gene
DNA replication fork pausing local	phenotype
DNA replication forks local	drug
DNA replication stress local	phenotype
doxycycline	drug
DSBs local	drug
DSBs within rDNA local	phenotype
EDTA	drug
ERC local	drug
ERC local	phenotype
ERC accumulation local	phenotype
ERC levels local	phenotype
estradiol	drug
ethidium bromide	drug
eukaryotic cells local	cohort
extrachromosomal rDNA circles local	drug
fermentation local	phenotype
fob1 local	gene
Fob1 local	gene
FOB1 local	gene
fob1Δ local	cohort
fob1Δ local	variant
fob1Δ cells local	cohort
GCN4 local	gene
genomic instability	phenotype
Genotypic change local	phenotype
glycerol	drug
Growth defect on glucose media local	phenotype
half sectors local	phenotype
haploid cells local	cohort
haploid cells local	phenotype
hazard rate of death local	phenotype
HCl	drug
high mortality local	phenotype
histone	drug
histone H4 K16 local	variant
homologous recombination local	phenotype
Human cancers local	cohort
ImageJ	drug
KANMX local	gene
KANMX local	variant
lead nitrate local	drug
LEU2 local	gene
life span local	phenotype
LOH	phenotype
LOH event local	variant
LOH events local	phenotype
LOH phenotype local	phenotype
LOH rate local	phenotype
LOH rates local	phenotype
longest-lived fraction local	cohort
longest-lived survivors local	cohort
Loss of Heterozygosity (LOH) local	phenotype
Loss of heterozygosity (LOH) phenotype local	phenotype
Loss of heterozygosity rate local	phenotype
loss of mitochondrial DNA local	phenotype
Loss of respiration competence local	phenotype
LRS4 local	gene
lrs4Δ local	variant
median RLS local	phenotype
MEP local	cohort
MEP background local	cohort
MEP cultures local	cohort
MEP strain local	cohort
MET15 local	gene
MET15 LOH local	phenotype
MET15 LOH phenotype local	phenotype
MET15 LOH rates local	phenotype
MET15 loss of heterozygosity local	phenotype
methionine	drug
mitochondrial function	phenotype
mitotic recombination	phenotype
MOPS	drug
mother cells local	phenotype
Mother Enrichment Program local	drug
mother population local	cohort
mtDNA	drug
mutator phenotype local	phenotype
NaOH	drug
Natural isolates of S. cerevisiae local	cohort
newborn daughter cells local	phenotype
NHC-Biotin local	drug
Non-reciprocal LOH local	phenotype
Non-reciprocal LOH events local	phenotype
non-reciprocal LOH pathway local	phenotype
NPR2 local	gene
NTS1 local	drug
old wild type cells local	cohort
oligonucleotide sequences local	drug
oxidative phosphorylation	phenotype
Partial uniparental disomy local	phenotype
Percoll Plus	drug
pGCN4 local	drug
Phosphorus-32 local	drug
pKAN-TETO2 local	drug
PKC1 local	gene
plasmids	drug
pLMI-tetR'S local	drug
pRS306 local	drug
pRS314-SIR2 local	drug
pRS400 local	drug
pRS401 local	drug
pRS402 local	drug
pUI-tTA-ADH1term-URA3 local	drug
rDNA local	drug
rDNA local	gene
rDNA array local	drug
rDNA array stability local	phenotype
rDNA recombination local	drug
rDNA recombination local	phenotype
rDNA repeats local	drug
rDNA stability local	phenotype
RecBCD local	drug
RecBCD exonuclease local	drug
Reciprocal LOH local	phenotype
Reciprocal LOH events local	phenotype
red colony sector local	phenotype
replicative age local	phenotype
replicative aging local	phenotype
replicative lifespan local	phenotype
Replicative Life Span local	phenotype
replicative life span (RLS) local	phenotype
respiration local	phenotype
respiration competence local	phenotype
Respiration-competent colony local	phenotype
Respiratory function local	phenotype
RFB sites local	drug
RLS local	phenotype
RNAlater local	drug
RRM3 local	gene
S288C local	cohort
S288C strain local	cohort
SAS2 local	gene
sas2Δ local	variant
SDS	drug
silent chromatin local	drug
Sir2	gene
SIR2hemi diploid local	cohort
SIR2OE local	cohort
SIR2OE strain local	cohort
sir2Δ local	variant
sir2Δ cells local	cohort
SSN6 local	gene
streptavidin beads local	drug
Supersignal West Pico local	drug
TCA local	drug
TET-FOB1 strain local	cohort
Tetracycline local	drug
TRP1 local	gene
tTA local	gene
tumor suppressor gene local	gene
UCC5179 local	cohort
UCC5181 local	cohort
UCC5185 local	cohort
UCC524 local	cohort
UCC7598-1 genomic DNA local	drug
UCC7629-1 genomic DNA local	drug
UCC809 local	cohort
UCC8832 local	cohort
UCC8839 local	cohort
UCC8840 local	cohort
UCC8844 local	cohort
UCC8908 local	cohort
UCC8909 local	cohort
UCC8910 local	cohort
UCC8913 local	cohort
UCC8914 local	cohort
UCC8915 local	cohort
UCC8917 local	cohort
UCC8918 local	cohort
unequal sister chromatid exchange (USCE) local	phenotype
UPD local	phenotype
UPD genotypes local	phenotype
URA3 local	gene
urea	drug
USCE local	phenotype
viability local	phenotype
VMA2 local	gene
VP16 local	drug
wild type cells local	cohort
wild type population local	cohort
wild type strain local	cohort
WT	cohort
YC media local	drug
yeast	cohort
yeast aging local	phenotype
yeast cells local	cohort
yeast strains local	cohort
YEPD local	drug
YEP+glycerol local	drug
young cells local	cohort
young cells local	phenotype
Young cells local	cohort

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In this knowledge base

Title	Year	PMID
Detectable clonal mosaicism from birth to old age and its relationship to cancer.	2012	22561516

External

Title	Authors	Journal	Year	Link
Age-dependent topoisomerase I depletion alters recruitment of rDNA silencing complexes.	Power LN et al.	—	2026	→
Replication fork blocking deficiency leads to a reduction of rDNA copy number in budding yeast.	Murai T et al.	—	2024	→
Contribution of Spontaneous Mutations to Quantitative and Molecular Variation at the Highly Repetitive rDNA Locus in Yeast.	Sharp NP et al.	—	2023	→
Senescence in yeast is associated with amplified linear fragments of chromosome XII rather than ribosomal DNA circle accumulation.	Zylstra A et al.	—	2023	→
Spt4 promotes cellular senescence by activating non-coding RNA transcription in ribosomal RNA gene clusters.	Yokoyama M et al.	—	2023	→
The increase in cell death rates in caloric restricted cells of the yeast helicase mutant rrm3 is Sir complex dependent.	Ivessa AS et al.	—	2023	→
Age-dependent aggregation of ribosomal RNA-binding proteins links deterioration in chromatin stability with challenges to proteostasis.	Paxman J et al.	—	2022	→
Breaking the aging epigenetic barrier.	Sikder S et al.	—	2022	→
rDNA array length is a major determinant of replicative lifespan in budding yeast.	Hotz M et al.	—	2022	→
The long and short of rDNA and yeast replicative aging.	Smith JS	—	2022	→
The role of NAD and NAD precursors on longevity and lifespan modulation in the budding yeast, Saccharomyces cerevisiae.	Odoh CK et al.	—	2022	→
Understanding the Impact of Industrial Stress Conditions on Replicative Aging in <i>Saccharomyces cerevisiae</i>.	Eigenfeld M et al.	—	2021	→
Cell organelles and yeast longevity: an intertwined regulation.	Banerjee R et al.	—	2020	→
Nicotinamide, Nicotinamide Riboside and Nicotinic Acid-Emerging Roles in Replicative and Chronological Aging in Yeast.	Orlandi I et al.	—	2020	→
Replicative aging is associated with loss of genetic heterogeneity from extrachromosomal circular DNA in<i>Saccharomyces cerevisiae</i>	Prada-Luengo I et al.	—	2020	—
Replicative aging is associated with loss of genetic heterogeneity from extrachromosomal circular DNA in Saccharomyces cerevisiae.	Prada-Luengo I et al.	—	2020	→
Stress and ageing in yeast.	Dawes IW et al.	—	2020	→
Defining the impact of mutation accumulation on replicative lifespan in yeast using cancer-associated mutator phenotypes.	Lee MB et al.	—	2019	→
Depletion of Limiting rDNA Structural Complexes Triggers Chromosomal Instability and Replicative Aging of <i>Saccharomyces cerevisiae</i>.	Fine RD et al.	—	2019	→
DNA damage checkpoint activation impairs chromatin homeostasis and promotes mitotic catastrophe during aging.	Crane MM et al.	—	2019	→
Yeast at the Forefront of Research on Ageing and Age-Related Diseases.	Sampaio-Marques B et al.	—	2019	→
A new experimental platform facilitates assessment of the transcriptional and chromatin landscapes of aging yeast.	Hendrickson DG et al.	—	2018	→
Daughters of the budding yeast from old mothers have shorter replicative lifespans but not total lifespans. Are DNA damage and rDNA instability the factors that determine longevity?	Molon M et al.	—	2018	→
Deregulation of the G1/S-phase transition is the proximal cause of mortality in old yeast mother cells.	Neurohr GE et al.	—	2018	→
Genomic Copy-Number Loss Is Rescued by Self-Limiting Production of DNA Circles.	Mansisidor A et al.	—	2018	→
Impaired cohesion and homologous recombination during replicative aging in budding yeast.	Pal S et al.	—	2018	→
The paths of mortality: how understanding the biology of aging can help explain systems behavior of single cells.	Crane MM et al.	—	2018	→
The yeast replicative aging model.	He C et al.	—	2018	→
Yeast lifespan variation correlates with cell growth and SIR2 expression.	Smith JT et al.	—	2018	→
Aggregation of the Whi3 protein, not loss of heterochromatin, causes sterility in old yeast cells.	Schlissel G et al.	—	2017	→
Antimutagenic, Antirecombinogenic, and Antitumor Effect of Amygdalin in a Yeast Cell-Based Test and Mammalian Cell Lines.	Todorova A et al.	—	2017	→
Heat stress promotes longevity in budding yeast by relaxing the confinement of age-promoting factors in the mother cell.	Baldi S et al.	—	2017	→
Identification of Genes in <i>Saccharomyces cerevisiae</i> that Are Haploinsufficient for Overcoming Amino Acid Starvation.	Bae NS et al.	—	2017	→
Increased genome instability is not accompanied by sensitivity to DNA damaging agents in aged yeast cells.	Novarina D et al.	—	2017	→
Multigenerational silencing dynamics control cell aging.	Li Y et al.	—	2017	→
Somatic recombination in adult tissues: What is there to learn?	Siudeja K et al.	—	2017	→
Absence of Non-histone Protein Complexes at Natural Chromosomal Pause Sites Results in Reduced Replication Pausing in Aging Yeast Cells.	Cabral M et al.	—	2016	→
Grabbing the genome by the NADs.	Matheson TD et al.	—	2016	→
Growth conditions that increase or decrease lifespan in Saccharomyces cerevisiae lead to corresponding decreases or increases in rates of interstitial deletions and non-reciprocal translocations.	Maxwell PH	—	2016	→
rDNA Copy Number Variants Are Frequent Passenger Mutations in Saccharomyces cerevisiae Deletion Collections and de Novo Transformants.	Kwan EX et al.	—	2016	→
Reproductive potential and instability of the rDNA region of the Saccharomyces cerevisiae yeast: Common or separate mechanisms of regulation?	Zadrag-Tecza R et al.	—	2016	→
The Nuts and Bolts of Transcriptionally Silent Chromatin in Saccharomyces cerevisiae.	Gartenberg MR et al.	—	2016	→
Evidence that mutation accumulation does not cause aging in Saccharomyces cerevisiae.	Kaya A et al.	—	2015	→
Preferential retrotransposition in aging yeast mother cells is correlated with increased genome instability.	Patterson MN et al.	—	2015	→
A sphingolipid-dependent diffusion barrier confines ER stress to the yeast mother cell.	Clay L et al.	—	2014	→
Budding yeast as a model organism to study the effects of age.	Denoth Lippuner A et al.	—	2014	→
Combining magnetic sorting of mother cells and fluctuation tests to analyze genome instability during mitotic cell aging in Saccharomyces cerevisiae.	Patterson MN et al.	—	2014	→
Mitochondria in ageing: there is metabolism beyond the ROS.	Breitenbach M et al.	—	2014	→
Nucleosome loss leads to global transcriptional up-regulation and genomic instability during yeast aging.	Hu Z et al.	—	2014	→
Quasi-programmed aging of budding yeast: a trade-off between programmed processes of cell proliferation, differentiation, stress response, survival and death defines yeast lifespan.	Arlia-Ciommo A et al.	—	2014	→
Ribosomal DNA and cellular senescence: new evidence supporting the connection between rDNA and aging.	Ganley AR et al.	—	2014	→
Role of SAGA in the asymmetric segregation of DNA circles during yeast ageing.	Denoth-Lippuner A et al.	—	2014	→
A genomic view of mosaicism and human disease.	Biesecker LG et al.	—	2013	→
Aging yeast cells undergo a sharp entry into senescence unrelated to the loss of mitochondrial membrane potential.	Fehrmann S et al.	—	2013	→
A growing role for hypertrophy in senescence.	Wright J et al.	—	2013	→
A natural polymorphism in rDNA replication origins links origin activation with calorie restriction and lifespan.	Kwan EX et al.	—	2013	→
Causes of genome instability.	Aguilera A et al.	—	2013	→
Cellular senescence in yeast is regulated by rDNA noncoding transcription.	Saka K et al.	—	2013	→
End-of-life cell cycle arrest contributes to stochasticity of yeast replicative aging.	Delaney JR et al.	—	2013	→
New approaches to an age-old problem.	Clay L et al.	—	2013	→
The cell biology of open and closed mitosis.	Boettcher B et al.	—	2013	→
An early age increase in vacuolar pH limits mitochondrial function and lifespan in yeast.	Hughes AL et al.	—	2012	→
Detectable clonal mosaicism from birth to old age and its relationship to cancer.	Laurie CC et al.	—	2012	→
DNA damage and DNA replication stress in yeast models of aging.	Burhans WC et al.	—	2012	→
Epigenetic modification of the repair donor regulates targeted gene correction.	Humbert O et al.	—	2012	→
Functional analyses of human DNA repair proteins important for aging and genomic stability using yeast genetics.	Aggarwal M et al.	—	2012	→
Mitotic exit and separation of mother and daughter cells.	Weiss EL	—	2012	→
Natural genetic variation in yeast longevity.	Stumpferl SW et al.	—	2012	→
Organelle segregation during mitosis: lessons from asymmetrically dividing cells.	Ouellet J et al.	—	2012	→
Osh6 overexpression extends the lifespan of yeast by increasing vacuole fusion.	Gebre S et al.	—	2012	→
Peroxiredoxins, gerontogenes linking aging to genome instability and cancer.	Nyström T et al.	—	2012	→
Replicative and chronological aging in Saccharomyces cerevisiae.	Longo VD et al.	—	2012	→
Gamete formation resets the aging clock in yeast.	Ünal E et al.	—	2011	→
Retrotransposition is associated with genome instability during chronological aging.	Maxwell PH et al.	—	2011	→
Running on empty: does mitochondrial DNA mutation limit replicative lifespan in yeast?: Mutations that increase the division rate of cells lacking mitochondrial DNA also extend replicative lifespan in Saccharomyces cerevisiae.	Dunn CD	—	2011	→