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:

Cell cycle

Checkpoint on the nuclear frontier

Nature volume 397, pages 104–105 (1999)Cite this article

Space is set to be the next frontier in cell-cycle research. Until now, the focus has been on how the cell cycle is regulated in time, by the synthesis and destruction of regulatory proteins such as the cyclins. But this is a one-dimensional view, and there is increasing evidence that the cell cycle is controlled by localizing specific regulators to the right place at the right time. An example of this is reported by Paul Russell and colleagues1 on page 172 of this issue. They show that, in the fission yeast Schizosaccharomyces pombe, the Cdc25 phosphatase — an essential regulator of mitosis — is exported from the nucleus in response to DNA damage. Export separates Cdc25 from its substrate, the cyclin B/Cdc2 kinase, thereby stopping cells from entering mitosis. Moreover, Cdc25 is exported from the nucleus by association with a protein called Rad24, which acts as an attachable nuclear-export sequence.

To maintain the integrity of the genome, DNA must be fully replicated and undamaged before mitosis can begin. So, the initiation of mitosis is carefully regulated, and the essential elements have been conserved through evolution2. The main target of this regulation is cyclin B/Cdc2. During interphase, this complex is kept inactive by the wee1 kinase, which phosphorylates Cdc2 on a conserved tyrosine residue (Y15) in the ATP-binding site. To initiate mitosis, the phosphate is then removed by Cdc25. DNA damage prevents cells from entering mitosis by enhancing phosphorylation of Y15, so keeping the cyclin B/Cdc2 turned off. This arrests the cells in the G2 phase at the ‘DNA-damage checkpoint’ (reviewed in ref. 3).

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

Figure 1: Regulation of mitosis in the fission yeast Schizosaccharomyces pombe.

References

  1. Lopez-Girona, A., Furnari, B., Mondesert, O. & Russell, P. Nature 397, 172–175 (1999).

    Article  ADS  CAS  Google Scholar 

  2. Nurse, P. Nature 344, 503–508 (1990).

    Article  ADS  CAS  Google Scholar 

  3. Elledge, S. J. Science 274, 1664–1672 (1996).

    Google Scholar 

  4. Muslin, A. J., Tanner, J. W., Allen, P. M. & Shaw, A. S. Cell 84, 889–897 (1996).

    Google Scholar 

  5. Furnari, B., Rhind, N. & Russell, P. Science 277, 1495–1497 (1997).

    Google Scholar 

  6. Peng, C. Y.et al. Science 277, 1501–1505 (1997).

    Google Scholar 

  7. Sanchez, Y.et al. Science 277, 1497–1501 (1997).

    Google Scholar 

  8. Hermeking, H.et al. Mol. Cell 1, 3–11 (1997).

    Google Scholar 

  9. Nurse, P. Cell 91, 865–867 (1997).

    Google Scholar 

  10. Hagting, A., Karlsson, C., Clute, P., Jackman, M. & Pines, J. EMBO J. 17, 4127–4138 (1998).

    Google Scholar 

  11. Toyoshima, F., Moriguchi, T., Wada, A., Fukuda, M. & Nishida, E. EMBO J. 17, 2728–2735 (1998).

    Google Scholar 

  12. Yang, J.et al. Genes Dev. 12, 2131–2143 (1998).

    Google Scholar 

  13. Petersen, B. O., Lukas, J., Sorensen, C. S., Bartek, J. & Helin, K. EMBO J. (in the press).

  14. Diehl, J. A., Zindy, F. & Sherr, C. J. Genes Dev. 11, 957–972 (1997).

    Google Scholar 

  15. Roth, J., Dobbelstein, M., Freedman, D. A., Shenk, T. & Levine, A. EMBO J. 17, 554–564 (1998).

    Google Scholar 

  16. Loeb, J. D.et al. Proc. Natl Acad. Sci. USA 92, 7647–7651 (1995).

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. the Wellcome/CRC Institute, Tennis Court Road, Cambridge, CB2 1QR, UK

    Jonathon Pines

Authors
  1. Jonathon Pines
    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

Pines, J. Checkpoint on the nuclear frontier. Nature 397, 104–105 (1999). https://doi.org/10.1038/16344

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1038/16344

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