Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • News & Views
  • Published:

The shuffling of a mortal coil

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).

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

References

  1. Weindruch, R. & Sohal, R.S. N. Engl. J. Med. 337 , 986–994 (1997).

    Article  CAS  Google Scholar 

  2. Johnson, F.B., Sinclair, D.A. & Guarente, L. Cell 96, 291– 302 (1999).

    Article  CAS  Google Scholar 

  3. Sinclair, D.A. & Guarente, L. Cell 91, 1033–1042 (1997).

    Article  CAS  Google Scholar 

  4. Yu, C.E. et al. Science, 373, 258–262 (1996).

    Article  Google Scholar 

  5. Defossez, P.A. et al. Mol. Cell (in press).

  6. Brewer, B.J. & Fangman, W.L. Cell 55, 637–643 (1988).

    Article  CAS  Google Scholar 

  7. Lin, Y.H. & Keil, R.L. Genetics 127, 31–38 (1991).

    CAS  PubMed  PubMed Central  Google Scholar 

  8. Kobayashi, T. & Horiuchi, T. Genes Cells 1, 465–474 (1996).

    Article  CAS  Google Scholar 

  9. Conrad-Webb, H. & Butow, R.A. Mol. Cell. Biol. 15, 2420–2428 ( 1995).

    Article  CAS  Google Scholar 

  10. Brewer, B.J., Lockshon, D.J. & Fangman, W.L. Cell 71, 267– 276 (1992).

    Article  CAS  Google Scholar 

  11. Kobayashi, T., Heck, D.J., Nomura, M. & Horiuchi, T. Genes Dev. 12, 3821–3830 (1998).

    Article  CAS  Google Scholar 

  12. Michel, B., Ehrlich, S.D. & Uzest, M. EMBO J. 16, 430– 438 (1997).

    Article  CAS  Google Scholar 

  13. Malkova, A., Ivanov, E.L. & Haber, J.E. Proc. Natl Acad. Sci. USA 93, 7131–7136 (1996).

    Article  CAS  Google Scholar 

  14. Morrow, D.M., Connelly, C. & Hieter, P. Genetics 147, 371– 382 (1997).

    CAS  PubMed  PubMed Central  Google Scholar 

  15. Gangloff, S. et al. Mol. Cell. Biol. 14, 8391– 8398 (1994).

    Article  CAS  Google Scholar 

  16. Rothstein, R. & Gangloff, S. Genome Res. 5, 421–426 (1995).

    Article  CAS  Google Scholar 

  17. Kim, R.A. & Wang, J.C. Cell 57, 975 –985 (1989).

    Article  CAS  Google Scholar 

  18. Nogi, Y., Yano, R. & Nomura, M. Proc. Natl Acad. Sci. USA 88, 3962 –3966 (1991).

    Article  CAS  Google Scholar 

  19. Zou, H. & Rothstein, R. Cell 90, 87–96 (1997).

    Article  CAS  Google Scholar 

  20. Gangloff, S., Zou, H. & Rothstein, R. EMBO J. 15, 1715– 1725 (1996).

    Article  CAS  Google Scholar 

Download references

Author information

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
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Serge Gangloff
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

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

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1038/8705

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing