Circular chromosome formation in a fission yeast mutant defective in two ATM homologues (original) (raw)

Nature Genetics volume 20, pages 203–206 (1998)Cite this article

Abstract

Telomeres, found at chromosomal ends, are essential for stable maintenance of linear chromosomes in eukaryotes. The ATM family of genes, including budding yeast TEL1 (Refs 1, 2 ), fission yeast rad3+ ( ref. 3 ) and human ATM (ref. 4 ), have been reported to be involved in telomere length regulation5,6,7 although the significance of the telomere phenotypes observed with the mutated genes remains elusive. We have cloned tel1+, another fission yeast ATM homologue, and found that a tel1rad3 double mutant lost all telomeric DNA sequences. Thus, the ATM homologues are essential in telomere maintenance. The mutant grew poorly and formed irregular-shaped colonies, probably due to chromosome instability, however, during prolonged culture of the double mutant, cells forming normal round-shaped colonies arose at a relatively high frequency. All three chromosomes in these derivative cells were circular and lacked telomeric sequences. To our knowledge, this is the first report of eukaryotic cells whose chromosomes are all circular. Upon meiosis, these derivative cells produced few viable spores. Therefore, the exclusively circular genome lacking telomeric sequences is proficient for mitotic growth, but does not permit meiosis.

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

Access options

Subscribe to this journal

Receive 12 print issues and online access

$259.00 per year

only $21.58 per issue

Buy this article

USD 39.95

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

Additional access options:

Similar content being viewed by others

Accession codes

Accessions

GenBank/EMBL/DDBJ

References

  1. Greenwell, P.W. et al. TEL1, a gene involved in controlling telomere length in S. cerevisiae, is homologous to the human ataxia telangiectasia gene. Cell 82, 823–829 (1995).
    Article CAS Google Scholar
  2. Morrow, D.M., Tagle, D.A., Shiloh, Y., Collins, F.S. & Hieter, P. TEL1, an S. cerevisiae homolog of the human gene mutated in ataxia telangiectasia, is functionally related to the yeast checkpoint gene MEC1. Cell 82, 831–840 (1995).
    Article CAS Google Scholar
  3. Bentley, N.J. et al. TL>The Schizosaccharomyces pombe rad3 checkpoint gene. EMBO J. 15, 6641–6651 ( 1996).
    Article CAS Google Scholar
  4. Savitsky, K. et al. A single ataxia telangiectasia gene with a product similar to PI-3 kinase. Science 268, 1749– 1753 (1995).
    Article CAS Google Scholar
  5. Dahlén, M., Olsson, T., Kanter-Smoler, G., Ramne, A. & Sunnerhagen, P. Regulation of telomere length by checkpoint genes in Schizosaccharomyces pombe. Mol. Cell. Biol. 9, 611–621 ( 1998).
    Article Google Scholar
  6. Metcalfe, J.A. et al. Accelerated telomere shortening in ataxia telangiectasia. Nature Genet. 13, 350–353 (1996).
    Article CAS Google Scholar
  7. Lustig, A.J. & Petes, T.D. Identification of yeast mutants with altered telomere structure. Proc. Natl Acad. Sci. USA 83, 1398–1402 (1986).
    Article CAS Google Scholar
  8. Singer, M.S. & Gottschling, D.E. TLC1: Template RNA component of Saccharomyces cerevisiae telomerase. Science 266, 404–409 (1994).
    Article CAS Google Scholar
  9. Counter, C.M., Meyerson, M., Eaton, E.N.G. & Weinberg, R.A. The catalytic subunit of yeast telomerase. Proc. Natl Acad. Sci. USA 94, 9202–9207 ( 1997).
    Article CAS Google Scholar
  10. Lundblad, V. & Blackburn, E.H. An alternative pathway for yeast telomere maintenance rescues est1 – senescence. Cell 73, 347–360 ( 1993).
    Article CAS Google Scholar
  11. Sugawara, N. DNA sequences at the telomeres of the fission yeast S. pombe. Thesis, Harvard Univ. (1989).
  12. Mizukami, T. et al. A 13 kb resolution cosmid map of the 14 Mb fission yeast genome by nonrandom sequence-tagged site mapping. Cell 73, 121–132 (1993).
    Article CAS Google Scholar
  13. Hoheisel, J.D. et al. High resolution cosmid and P1 maps spanning the 14 Mb genome of the fission yeast S. pombe. Cell 73, 109–120 (1993).
    Article CAS Google Scholar
  14. Dingwall, A., Shapiro, L. & Ely, B. Analysis of bacterial genome organization and replication using pulsed-field gel electrophoresis. Methods 1, 160–168 (1990).
    Article CAS Google Scholar
  15. Mortimer, R.K., Game, J.C., Bell, M. & Contopoulou, C.R. Use of pulsed-field gel electrophoresis to study the chromosomes of Saccharomyces and other yeasts. Methods 1, 169– 179 (1990).
    Article CAS Google Scholar
  16. Hiraoka, Y., Toda, T. & Yanagida, M. The NDA3 gene of fission yeast encodes ß-tubulin: a cold-sensitive nda3 mutation reversibly blocks spindle formation and chromosome movement in mitosis. Cell 39, 349–358 (1984).
    Article CAS Google Scholar
  17. Niwa, O. & Yanagida, M. Triploid meiosis and aneuploidy in Schizosaccharomyces pombe: an unstable aneuploid disomic for chromosome III. Curr. Genet. 9, 463– 470 (1985).
    Article Google Scholar
  18. Fan, J.B., Rochet, M., Gaillardin, C. & Smith, C.L. Detection and characterization of a ring chromosome in the fission yeast Schizosaccharomyces pombe. Nucleic Acids Res. 20 , 5943–5945 (1992).
    Article CAS Google Scholar
  19. Haber, J.E., Thorburn, P.C. & Rogers, D. Meiotic and mitotic behavior of dicentric chromosomes in Saccharomyces cerevisiae. Genetics 106, 185–205 (1984).
    CAS PubMed PubMed Central Google Scholar
  20. Murakami, S., Yanagida, M. & Niwa, O. A large circular minichromosome of Schizosaccharomyces pombe requires a high dose of type II DNA topoisomerase for its stabilization . Mol. Gen. Genet. 246, 671– 679 (1995).
    Article CAS Google Scholar
  21. Therman, E. & Susman, M. Human Chromosomes (Springer-Verlag, New York, 1993).
    Book Google Scholar
  22. Pandita, T.K., Pathak, S. & Geard, C.R. Chromosome end associations, telomeres and telomerase activity in ataxia telangiectasia cells. Cytogenet. Cell Genet. 71, 86–93 ( 1995).
    Article CAS Google Scholar
  23. Chikashige, Y. et al. Telomere-led premeiotic chromosome movement in fission yeast . Science 264, 270–273 (1994).
    Article CAS Google Scholar
  24. Chikashige, Y. et al. Meiotic nuclear reorganization: switching the position of centromeres and telomeres in the fission yeast Schizosaccharomyces pombe . EMBO J. 16, 193–202 (1997).
    Article CAS Google Scholar
  25. Cooper, J.P., Watanabe, Y. & Nurse, P. Fission yeast Taz1 protein is required for meiotic telomere clustering and recombination. Nature 392, 828–831 (1998).
    Article CAS Google Scholar
  26. Nimmo, E.R., Pidoux, A.L., Perry, P.E. & Allshire, R.C. Defective meiosis in telomere-silencing mutants of Schizosaccharomyces pombe. Nature 392, 825– 828 (1998).
    Article CAS Google Scholar
  27. McClintock, B. The stability of broken ends of chromosomes in Zea Mays. Genetics 26, 234–282 ( 1941).
    CAS PubMed PubMed Central Google Scholar
  28. Alfa, C., Fantes, P., Hyams, J., McLeod, M. & Warbrick, E. Experiments with Fission Yeast, (Cold Spring Harbor Laboratory Press, Cold Spring Harbor, New York, 1993).
    Google Scholar

Download references

Acknowledgements

We thank E.A. Kamei, T. Shibata and L. Guarente for critical reading of and comments on the manuscript, N. Munakata for γ-ray irradiation experiments and O. Niwa for providing the nda3-KM311 mutant and for helpful discussion. The excellent secretarial work of M. Fukuda is acknowledged. This work was supported by a Grant-in-Aid for Cancer Research and a Grant-in-Aid for Scientific Research on Priority Areas from the Ministry of Education, Science, Sports and Culture of Japan, a Grant-in-Aid of Special Coordination Funds for Promoting Science and Technology from the Science and Technology Agency of Japan and a Grant-in-Aid from the Mitsubishi Foundation. T.N. was supported by a JSPS Research Fellowship for Young Scientists.

Author information

Authors and Affiliations

  1. Department of Life Science, Tokyo Institute of Technology, 4259 Nagatsuta, Midori-ku, 226-8501, Yokohama, Japan
    Taku Naito, Akira Matsuura & Fuyuki Ishikawa

Authors

  1. Taku Naito
  2. Akira Matsuura
  3. Fuyuki Ishikawa

Corresponding author

Correspondence toFuyuki Ishikawa.

Rights and permissions

About this article

Cite this article

Naito, T., Matsuura, A. & Ishikawa, F. Circular chromosome formation in a fission yeast mutant defective in two ATM homologues.Nat Genet 20, 203–206 (1998). https://doi.org/10.1038/2517

Download citation

This article is cited by