The shuffling of a mortal coil (original) (raw)

Nature Genetics volume 22, pages 4–6 (1999)Cite this article

The spectre of death—and perhaps of the riches to be gained by delaying it—has inspired many researchers to consider the mechanism(s) of ageing. While studies using mice, worms and fruit flies suggest that a restrictive diet contributes to life extension1, the molecular underpinnings of ageing remain elusive2,3. Work carried out by Leonard Guarente and colleagues has previously demonstrated that a decrease in lifespan of Saccharomyces cerevisiae correlates with the formation of extrachromosomal ribosomal DNA (rDNA) circles (ERCs). This observation is relevant to the human condition, as the same correlation is observed in yeast cells deficient in SGS1, the yeast orthologue of the gene mutated in people with Werner syndrome4 (who also show accelerated ageing).Box 1

The most recent contribution5 of Guarente, Defossez and colleagues concerns FOB1, which encodes a protein required for the unidirectional replication fork block6 (RFB) observed in the rDNA tandem array. They show that Fob1p is a nucleolar protein whose absence results in a dramatic decrease of ERCs in ageing cells. In fact, fob1 mutants have a significantly increased lifespan, supporting the view that the generation of ERCs correlates with ageing. Notably, mutations in FOB1 result in a decrease in the rate of recombination in rDNA(Refs 7,8).

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Authors and Affiliations

  1. Department of Genetics and Development, Columbia University, College of Physicians & Surgeons, New York, 10032, New York, USA
    Rodney Rothstein
  2. CEA de Fontenay-aux-roses, UMR 217 CNRS-CEA, 92265, Fontenay-aux-roses, France
    Serge Gangloff

Authors

  1. Rodney Rothstein
  2. Serge Gangloff

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Rothstein, R., Gangloff, S. The shuffling of a mortal coil.Nat Genet 22, 4–6 (1999). https://doi.org/10.1038/8705

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