Letter | Published:

Fused sister kinetochores initiate the reductional division in meiosis I

Nature Cell Biology volume 11, pages 11031108 (2009) | Download Citation

Subjects

Abstract

During meiosis I the genome is reduced to the haploid content by a coordinated reductional division event. Homologous chromosomes align, recombine and segregate while the sister chromatids co-orient and move to the same pole1,2. Several data suggest that sister kinetochores co-orient early in metaphase I and that sister chromatid cohesion (which requires Rec8 and Shugoshin) supports monopolar orientation. Nevertheless, it is unclear how the sister kinetochores function as single unit during this period. A gene (monopolin)3 with a co-orienting role was identified in Saccharomyces cerevisiae; however, it does not have the same function in fission yeast4 and no similar genes have been found in other species. Here we pursue this issue using knockdown mutants of the core kinetochore protein MIS12 (minichromosome instability 12). MIS12 binds to base of the NDC80 complex, which in turn binds directly to microtubules5,6,7. In maize plants with systemically reduced levels of MIS12, a visible MIS12–NDC80 bridge between sister kinetochores at meiosis I is broken. Kinetochores separate and orient randomly in metaphase I, causing chromosomes to stall in anaphase due to normal cohesion, marked by Shugoshin, between the chromatids. The data establish that sister kinetochores in meiosis I are fused by a shared microtubule-binding face and that this direct linkage is required for reductional division.

Access optionsAccess options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

References

  1. 1.

    , & Un menage a quatre: the molecular biology of chromosome segregation in meiosis. Cell 112, 423–440 (2003).

  2. 2.

    & Emerging roles for centromeres in meiosis I chromosome segregation. Nature Rev. Genet. 9 (12), 899–910 (2008).

  3. 3.

    et al. Functional genomics identifies monopolin: a kinetochore protein required for segregation of homologs during meiosis I. Cell 103, 1155–1168 (2000).

  4. 4.

    et al. Kinetochore recruitment of two nucleolar proteins is required for homolog segregation in meiosis I. Dev. Cell 4, 535–548 (2003).

  5. 5.

    , , & Human centromere chromatin protein hMis12, essential for equal segregation, is independent of CENP-A loading pathway. J. Cell Biol. 160, 25–39 (2003).

  6. 6.

    , , , & The human Mis12 complex is required for kinetochore assembly and proper chromosome segregation. J. Cell Biol. 173, 9–17 (2006).

  7. 7.

    & Molecular architecture of the kinetochore-microtubule interface. Nature Rev. Mol. Cell Biol. 9, 33–46 (2008).

  8. 8.

    & The kinetochore protein Moa1 enables cohesion-mediated monopolar attachment at meiosis I. Cell 123, 803–817 (2005).

  9. 9.

    , & Kinetochore geometry defined by cohesion within the centromere. Nature 458, 852–858 (2009).

  10. 10.

    & Maize NDC80 is a constitutive feature of the central kinetochore. Chromosome Res. 15, 767–775 (2007).

  11. 11.

    et al. Centromeric retroelements and satellites interact with maize kinetochore protein CENH3. Plant Cell 14, 2825–2836 (2002).

  12. 12.

    , , , & A maize homolog of mammalian CENPC is a constitutive component of the inner kinetochore. Plant Cell 11, 1227–1238 (1999).

  13. 13.

    et al. Aurora controls sister kinetochore mono-orientation and homolog bi-orientation in meiosis-I. EMBO J. 26, 4475–4486 (2007).

  14. 14.

    , & The conserved kinetochore protein shugoshin protects centromeric cohesion during meiosis. Nature 427, 510–517 (2004).

  15. 15.

    et al. Two fission yeast homologs of Drosophila Mei-S332 are required for chromosome segregation during meiosis I and II. Curr. Biol. 14, 287–301 (2004).

  16. 16.

    , , & The Drosophila mei-S332 gene promotes sister-chromatid cohesion in meiosis following kinetochore differentiation. Genetics 130, 827–841 (1992).

  17. 17.

    et al. A REC8-dependent plant Shugoshin is required for maintenance of centromeric cohesion during meiosis and has no mitotic functions. Curr. Biol. 15, 948–954 (2005).

  18. 18.

    et al. Unified mode of centromeric protection by shugoshin in mammalian oocytes and somatic cells. Nature Cell Biol. 10, 42–52 (2008).

  19. 19.

    & Differentiation of the synaptonemal complex and the kinetochore in Locusta spermatocytes studied by whole mount electron microscopy. Chromosoma 44, 231–253 (1973).

  20. 20.

    & Chromosome segregation during meiosis: building an unambivalent bivalent. Curr. Top. Dev. Biol. 37, 263–299 (1998).

  21. 21.

    Meiotic chromosome organization and segregation in plants. Ann. Rev. Plant Phys. Plant Mol. Biol. 49, 371–395 (1998).

  22. 22.

    et al. Involvement of the cohesin Rad21 and SCP3 in monopolar attachment of sister kinetochores during mouse meiosis I. J. Cell Sci. 117, 1221–1234 (2004).

  23. 23.

    Synaptonemal complexes: Structure and function. Curr. Opin. Cell Biol. 8, 389–396 (1996).

  24. 24.

    & The reduction of chromosome number in meiosis is determined by properties built into the chromosomes. J. Cell Biol. 150, 1223–1232 (2000).

  25. 25.

    & Meiosis: Rec8 is the reason for cohesion. Nature Cell Biol. 1, E125–E127 (1999).

  26. 26.

    et al. A central role for cohesins in sister chromatid cohesion, formation of axial elements, and recombination during yeast meiosis. Cell 98, 91–103 (1999).

  27. 27.

    et al. Alleles of afd1 dissect REC8 functions during meiotic prophase I. J. Cell Sci. 119, 3306–3315 (2006).

  28. 28.

    Kinetochore structure and its role in chromosome orientation during the first meiotic division in male D. melanogaster. Cell 25, 591–602 (1981).

  29. 29.

    & To err (meiotically) is human: the genesis of human aneuploidy. Nature Rev. Genet. 2, 280–291 (2001).

  30. 30.

    , & Characterization of a Mis12 homologue in Arabidopsis thaliana. Chromosome Res. 13, 827–834 (2005).

  31. 31.

    , , , & Phosphoserines on maize centromeric histone H3 and histone H3 demarcate the centromere and pericentromere during chromosome segregation. Plant Cell 17, 572–583 (2005).

  32. 32.

    et al. Assessing the efficiency of RNA interference for maize functional genomics. Plant Physiol. 143, 1441–1451 (2007).

Download references

Acknowledgements

We thank X. Zhang for her support and help with RT-PCR and image analysis, H. Tang for help with statistics, R. Wang for providing Shugoshin antibodies, A. Luce for technical support and C. Topp and L. Kanizay for helpful comments. This study was supported by a grant from the National Science Foundation to R.K.D. (0421671).

Author information

Affiliations

  1. Department of Plant Biology, University of Georgia, Athens, GA 30602, USA.

    • Xuexian Li
    •  & R. Kelly Dawe
  2. Department of Genetics, University of Georgia, Athens, GA 30602, USA.

    • R. Kelly Dawe

Authors

  1. Search for Xuexian Li in:

  2. Search for R. Kelly Dawe in:

Contributions

X.L. performed experimental work and data analysis. R.K.D. focused on planning and interpretation.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to R. Kelly Dawe.

Supplementary information

PDF files

  1. 1.

    Supplementary Information

    Supplementary Information

About this article

Publication history

Received

Accepted

Published

DOI

https://doi.org/10.1038/ncb1923

Further reading