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Natural polymorphism in BUL2 links cellular amino acid availability with chronological aging and telomere maintenance in yeast.

PLoS genetics | 2011

Aging and longevity are considered to be highly complex genetic traits. In order to gain insight into aging as a polygenic trait, we employed an outbred Saccharomyces cerevisiae model, generated by crossing a vineyard strain RM11 and a laboratory strain S288c, to identify quantitative trait loci that control chronological lifespan. Among the major loci that regulate chronological lifespan in this cross, one genetic linkage was found to be congruent with a previously mapped locus that controls telomere length variation. We found that a single nucleotide polymorphism in BUL2, encoding a component of an ubiquitin ligase complex involved in trafficking of amino acid permeases, controls chronological lifespan and telomere length as well as amino acid uptake. Cellular amino acid availability changes conferred by the BUL2 polymorphism alter telomere length by modulating activity of a transcription factor Gln3. Among the GLN3 transcriptional targets relevant to this phenotype, we identified Wtm1, whose upregulation promotes nuclear retention of ribonucleotide reductase (RNR) components and inhibits the assembly of the RNR enzyme complex during S-phase. Inhibition of RNR is one of the mechanisms by which Gln3 modulates telomere length. Identification of a polymorphism in BUL2 in this outbred yeast population revealed a link among cellular amino acid availability, chronological lifespan, and telomere length control.

Pubmed ID: 21901113 RIS Download

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Associated grants

  • Agency: NCI NIH HHS, United States
    Id: CA103728-03
  • Agency: NCI NIH HHS, United States
    Id: T32 CA009229
  • Agency: NIA NIH HHS, United States
    Id: 2P30AG013280-16
  • Agency: NCI NIH HHS, United States
    Id: CA129132
  • Agency: NCI NIH HHS, United States
    Id: P20 CA103728
  • Agency: NCI NIH HHS, United States
    Id: R01 CA129132
  • Agency: NCI NIH HHS, United States
    Id: T32 CA09229
  • Agency: NIA NIH HHS, United States
    Id: P30 AG013280

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RRID:SCR_001224

A contract research organization providing drug development and animal testing services. Under the name Covance Research Products Inc., based in Denver, Pennsylvania, the company also deals in the import, breeding and sale of laboratory animals. It breeds dogs, rabbits, guinea pigs, non-human primates, and pigs, and runs the largest non-human primate laboratory in Germany. (Wikipedia)

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