Evidence map›Paper›PMID 21436897›Full record

ArticlePLoS genetics2011

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

Derek L Lindstrom, Christina K Leverich, Kiersten A Henderson, Daniel E Gottschling

Open access · goldAbstract read
In one paragraph

Article in PLoS genetics, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.

0numbers the graph read from it
0cells of the map it votes in
57citing papers in PubMed
4.7field-weighted citation impact, top 4% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

57 citing papers in PubMed, 102 citations in OpenAlex.

  1. Article
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  7. The long and short of rDNA and yeast replicative aging.Proceedings of the National Academy of Sciences of the United States of America · 2022
    Article
  8. rDNA array length is a major determinant of replicative lifespan in budding yeast.Proceedings of the National Academy of Sciences of the United States of America · 2022
    Article
  9. Review
  10. Breaking the aging epigenetic barrier.Frontiers in cell and developmental biology · 2022
    Review
  11. Review
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  13. Review
  14. Review
  15. Article
  16. Article
  17. Defining the impact of mutation accumulation on replicative lifespan in yeast using cancer-associated mutator phenotypes.Proceedings of the National Academy of Sciences of the United States of America · 2019
    Article
  18. Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

4 authors at 2 institutions in 2 countries.

Derek L LindstromDivision of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
Christina K Leverich
Kiersten A Henderson
Daniel E Gottschling
Fred Hutch Cancer Center · USCape Town HVTN Immunology Laboratory / Hutchinson Centre Research Institute of South Africa · ZA

Funding

Chromosome Metabolism and Cancer Training GrantT32CA009657 · NCI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI EISENMAN, ROBERT NEIL · 1991 to 2020
$7.6M
Mechanism of increase genomic instability in aging yeastR01AG023779 · NIA · FRED HUTCHINSON CANCER RESEARCH CENTER · PI PARKHURST, SUSAN M · 2004 to 2019
$4.2M
Dissecting the mechanism of increased genomic instability in aging yeastR37AG023779 · NIA · FRED HUTCHINSON CANCER RESEARCH CENTER · PI GOTTSCHLING, DANIEL E. · 2010 to 2015
$2.9M
NCI NIH HHS T32 CA009657NCI NIH HHS T32 CA09657NIA NIH HHS AG023779NIA NIH HHS R01 AG023779NIA NIH HHS R37 AG023779
6 · The paper itself

Abstract

Somatic mutations contribute to the development of age-associated disease. In earlier work, we found that, at high frequency, aging Saccharomyces cerevisiae diploid cells produce daughters without mitochondrial DNA, leading to loss of respiration competence and increased loss of heterozygosity (LOH) in the nuclear genome. Here we used the recently developed Mother Enrichment Program to ask whether aging cells that maintain the ability to produce respiration-competent daughters also experience increased genomic instability. We discovered that this population exhibits a distinct genomic instability phenotype that primarily affects the repeated ribosomal RNA gene array (rDNA array). As diploid cells passed their median replicative life span, recombination rates between rDNA arrays on homologous chromosomes progressively increased, resulting in mutational events that generated LOH at >300 contiguous open reading frames on the right arm of chromosome XII. We show that, while these recombination events were dependent on the replication fork block protein Fob1, the aging process that underlies this phenotype is Fob1-independent. Furthermore, we provide evidence that this aging process is not driven by mechanisms that modulate rDNA recombination in young cells, including loss of cohesion within the rDNA array or loss of Sir2 function. Instead, we suggest that the age-associated increase in rDNA recombination is a response to increasing DNA replication stress generated in aging cells.

Indexed as

Genes, rRNARecombination, GeneticChromosomes, FungalCysteine SynthaseDNA-Binding ProteinsDNA, RibosomalLoss of HeterozygosityMitosisSaccharomyces cerevisiaeSaccharomyces cerevisiae ProteinsSilent Information Regulator Proteins, Saccharomyces cerevisiaeSirtuin 2Cysteine SynthaseDNA-Binding ProteinsDNA, RibosomalFOB1 protein, S cerevisiaeMET17 protein, S cerevisiaeSaccharomyces cerevisiae ProteinsSilent Information Regulator Proteins, Saccharomyces cerevisiaeSIR2 protein, S cerevisiaeSirtuin 2

Identifiers

PMID21436897
PMCPMC3060066
OpenAlexW1970998722

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.