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.

  • Letter
  • Published:

The spindle checkpoint rescues the meiotic segregation of chromosomes whose crossovers are far from the centromere

Abstract

Improper meiotic chromosome segregation causes conditions such as Down's syndrome1. Recombination promotes proper chromosome segregation in meiosis I; chromosomes without crossovers near the centromere are more likely to segregate to the same spindle pole (nondisjoin). Here we have used budding yeast to determine whether the spindle checkpoint promotes segregation of such chromosomes. In checkpoint-defective mad2Δ cells, properly segregating chromosomes have more crossovers near the centromere than their wild-type counterparts, and an artificial tether that holds chromosomes together suppresses nondisjunction as long as the tether is near the centromere. The tether partially rescues the segregation of chromosomes that lack crossovers.

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

Access options

Buy this article

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

Figure 1: Visualizing meiosis in yeast.
Figure 2: Chromosomes that disjoin properly in mad2Δ cells have more crossovers near the centromere as compared with wild-type cells.
Figure 3: The tetramerizing Lac repressor suppresses meiotic nondisjunction in mad2Δ cells.

Similar content being viewed by others

References

  1. Lamb, N.E., Sherman, S.L. & Hassold, T.J. Effect of meiotic recombination on the production of aneuploid gametes in humans. Cytogenet. Genome Res. 111, 250–255 (2005).

    Article  CAS  PubMed  Google Scholar 

  2. Gerton, J.L. & Hawley, R.S. Homologous chromosome interactions in meiosis: diversity amidst conservation. Nat. Rev. Genet. 6, 477–487 (2005).

    Article  CAS  PubMed  Google Scholar 

  3. Pinsky, B.A. & Biggins, S. The spindle checkpoint: tension versus attachment. Trends Cell Biol. 15, 486–493 (2005).

    Article  CAS  PubMed  Google Scholar 

  4. Nicklas, R.B. Chromosome micromanipulation. II. Induced reorientation and the experimental control of segregation in meiosis. Chromosoma 21, 17–50 (1967).

    Article  CAS  PubMed  Google Scholar 

  5. Shonn, M.A., Murray, A.L. & Murray, A.W. Spindle checkpoint component Mad2 contributes to biorientation of homologous chromosomes. Curr. Biol. 13, 1979–1984 (2003).

    Article  CAS  PubMed  Google Scholar 

  6. Cheslock, P.S., Kemp, B.J., Boumil, R.M. & Dawson, D.S. The roles of MAD1, MAD2 and MAD3 in meiotic progression and the segregation of nonexchange chromosomes. Nat. Genet. 37, 756–760 (2005).

    Article  CAS  PubMed  Google Scholar 

  7. Gilliland, W.D., Wayson, S.M. & Hawley, R.S. The meiotic defects of mutants in the Drosophila mps1 gene reveal a critical role of Mps1 in the segregation of achiasmate homologs. Curr. Biol. 15, 672–677 (2005).

    Article  CAS  PubMed  Google Scholar 

  8. Koehler, K.E. et al. Spontaneous X chromosome MI and MII nondisjunction events in Drosophila melanogaster oocytes have different recombinational histories. Nat. Genet. 14, 406–414 (1996).

    Article  CAS  PubMed  Google Scholar 

  9. Lamb, N.E. et al. Susceptible chiasmate configurations of chromosome 21 predispose to non-disjunction in both maternal meiosis I and meiosis II. Nat. Genet. 14, 400–405 (1996).

    Article  CAS  PubMed  Google Scholar 

  10. Mortimer, R.K., Schild, D., Contopoulou, C.R. & Kans, J.A. Genetic map of Saccharomyces cerevisiae, edition 10. Yeast 5, 321–403 (1989).

    Article  CAS  PubMed  Google Scholar 

  11. Kaback, D.B., Steensma, H.Y. & de Jonge, P. Enhanced meiotic recombination on the smallest chromosome of Saccharomyces cerevisiae. Proc. Natl. Acad. Sci. USA 86, 3694–3698 (1989).

    Article  CAS  PubMed  Google Scholar 

  12. Shonn, M.A., McCarroll, R. & Murray, A.W. Requirement of the spindle checkpoint for proper chromosome segregation in budding yeast meiosis. Science 289, 300–303 (2000).

    Article  CAS  PubMed  Google Scholar 

  13. Gu, Z. et al. Elevated evolutionary rates in the laboratory strain of Saccharomyces cerevisiae. Proc. Natl. Acad. Sci. USA 102, 1092–1097 (2005).

    Article  CAS  PubMed  Google Scholar 

  14. Winzeler, E.A. et al. Genetic diversity in yeast assessed with whole-genome oligonucleotide arrays. Genetics 163, 79–89 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

  15. Cherry, J.M. et al. Genetic and physical maps of Saccharomyces cerevisiae. Nature 387, 67–73 (1997).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Kramer, H. et al. lac repressor forms loops with linear DNA carrying two suitably spaced lac operators. EMBO J. 6, 1481–1491 (1987).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Chen, J. & Matthews, K.S. Subunit dissociation affects DNA binding in a dimeric lac repressor produced by C-terminal deletion. Biochemistry 33, 8728–8735 (1994).

    Article  CAS  PubMed  Google Scholar 

  18. Straight, A.F., Belmont, A.S., Robinett, C.C. & Murray, A.W. GFP tagging of budding yeast chromosomes reveals that protein-protein interactions can mediate sister chromatid cohesion. Curr. Biol. 6, 1599–1608 (1996).

    Article  CAS  PubMed  Google Scholar 

  19. Maxfield Boumil, R., Kemp, B., Angelichio, M., Nilsson-Tillgren, T. & Dawson, D.S. Meiotic segregation of a homeologous chromosome pair. Mol. Genet. Genomics 268, 750–760 (2003).

    CAS  PubMed  Google Scholar 

  20. Keeney, S., Giroux, C.N. & Kleckner, N. Meiosis-specific DNA double-strand breaks are catalyzed by Spo11, a member of a widely conserved protein family. Cell 88, 375–384 (1997).

    Article  CAS  PubMed  Google Scholar 

  21. Bergerat, A. et al. An atypical topoisomerase II from Archaea with implications for meiotic recombination. Nature 386, 414–417 (1997).

    Article  CAS  PubMed  Google Scholar 

  22. Cha, R.S., Weiner, B.M., Keeney, S., Dekker, J. & Kleckner, N. Progression of meiotic DNA replication is modulated by interchromosomal interaction proteins, negatively by Spo11p and positively by Rec8p. Genes Dev. 14, 493–503 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  23. Diaz, R.L., Alcid, A.D., Berger, J.M. & Keeney, S. Identification of residues in yeast Spo11p critical for meiotic DNA double-strand break formation. Mol. Cell. Biol. 22, 1106–1115 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Weiner, B.M. & Kleckner, N. Chromosome pairing via multiple interstitial interactions before and during meiosis in yeast. Cell 77, 977–991 (1994).

    Article  CAS  PubMed  Google Scholar 

  25. Kemp, B., Boumil, R.M., Stewart, M.N. & Dawson, D.S. A role for centromere pairing in meiotic chromosome segregation. Genes Dev. 18, 1946–1951 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Tsubouchi, T. & Roeder, G.S. A synaptonemal complex protein promotes homology-independent centromere coupling. Science 308, 870–873 (2005).

    Article  CAS  PubMed  Google Scholar 

  27. Kiburz, B.M. et al. The core centromere and Sgo1 establish a 50-kb cohesin-protected domain around centromeres during meiosis I. Genes Dev. 19, 3017–3030 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Blat, Y. & Kleckner, N. Cohesins bind to preferential sites along yeast chromosome III, with differential regulation along arms versus the centric region. Cell 98, 249–259 (1999).

    Article  CAS  PubMed  Google Scholar 

  29. Rockmill, B., Voelkel-Meiman, K. & Roeder, G.S. Centromere-proximal crossovers are associated with precocious separation of sister chromatids during meiosis in Saccharomyces cerevisiae. Genetics 174, 1745–1754 (2006).

    Article  PubMed  PubMed Central  Google Scholar 

  30. Padmore, R., Cao, L. & Kleckner, N. Temporal comparison of recombination and synaptonemal complex formation during meiosis in S. cerevisiae. Cell 66, 1239–1256 (1991).

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We thank A. Amon, D. Dawson, M. Dorer, R.S. Hawley, J. Leu, T. Salmon, F. Solomon and members of the Murray laboratory for critical reading of the manuscript; D. Dawson, J. Leu, A. Segrè and D. Thompson for discussions; and S. Keeney (Memorial Sloan-Kettering Cancer Center) and D. Dawson (Oklahoma Medical Research Foundation) for strains. This work was supported by a US National Institutes of Health (NIH) National Research Service Award fellowship to S.L. and an NIH grant to A.W.M. (GM 055840).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Soni Lacefield.

Supplementary information

Supplementary Text and Figures

Supplementary Tables 1–2 (PDF 98 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Lacefield, S., Murray, A. The spindle checkpoint rescues the meiotic segregation of chromosomes whose crossovers are far from the centromere. Nat Genet 39, 1273–1277 (2007). https://doi.org/10.1038/ng2120

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/ng2120

This article is cited by

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