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The conserved kinetochore protein shugoshin protects centromeric cohesion during meiosis

Abstract

Meiosis comprises a pair of specialized nuclear divisions that produce haploid germ cells. To accomplish this, sister chromatids must segregate together during the first meiotic division (meiosis I), which requires that sister chromatid cohesion persists at centromeres. The factors that protect centromeric cohesion during meiosis I have remained elusive. Here we identify Sgo1 (shugoshin), a protector of the centromeric cohesin Rec8 in fission yeast. We also identify a homologue of Sgo1 in budding yeast. We provide evidence that shugoshin is widely conserved among eukaryotes. Moreover, we identify Sgo2, a paralogue of shugoshin in fission yeast, which is required for faithful mitotic chromosome segregation. Localization of Sgo1 and Sgo2 at centromeres requires the kinase Bub1, identifying shugoshin as a crucial target for the kinetochore function of Bub1. These findings provide insights into the evolution of meiosis and kinetochore regulation during mitosis and meiosis.

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Figure 1: Co-expression of Sgo1 and Rec8 causes failure of sister chromatid separation during mitosis.
Figure 2: Sgo1 is required to protect Rec8 and thereby cohesion at centromeres during anaphase of meiosis I.
Figure 3: Sgo1 localizes at pericentromeric regions during meiosis I.
Figure 4: Sgo2 has a crucial role in mitotic division at the kinetochore.
Figure 5: Analysis of budding yeast shugoshin ScSgo1.
Figure 6: Alignment of the amino-terminal coiled-coil regions and C-terminal basic regions of shugoshin-like proteins in various organisms.

References

  1. Nasmyth, K. Disseminating the genome: joining, resolving, and separating sister chromatids during mitosis and meiosis. Annu. Rev. Genet. 35, 673–745 (2001)

    CAS  Article  Google Scholar 

  2. Koshland, D. E. & Guacci, V. Sister chromatid cohesion: the beginning of a long and beautiful relationship. Curr. Opin. Cell Biol. 12, 297–301 (2000)

    CAS  Article  Google Scholar 

  3. Uhlmann, F. Chromosome cohesion and separation: from men and molecules. Curr. Biol. 13, R104–R114 (2003)

    CAS  Article  Google Scholar 

  4. Lee, J. Y. & Orr-Weaver, T. L. The molecular basis of sister-chromatid cohesion. Annu. Rev. Cell Dev. Biol. 17, 753–777 (2001)

    CAS  Article  Google Scholar 

  5. Hirano, T. The ABCs of SMC proteins: two-armed ATPases for chromosome condensation, cohesion, and repair. Genes Dev. 16, 399–414 (2002)

    CAS  Article  Google Scholar 

  6. Klein, F. 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)

    CAS  Article  Google Scholar 

  7. Parisi, S. et al. Rec8p, a meiotic recombination and sister chromatid cohesion phosphoprotein of the Rad21p family, conserved from fission yeast to humans. Mol. Cell. Biol. 19, 3515–3528 (1999)

    CAS  Article  Google Scholar 

  8. Watanabe, Y. & Nurse, P. Cohesin Rec8 is required for reductional chromosome segregation at meiosis. Nature 400, 461–464 (1999)

    ADS  CAS  Article  Google Scholar 

  9. Pasierbek, P. et al. A Caenorhabditis elegans cohesion protein with functions in meiotic chromosome pairing and disjunction. Genes Dev. 15, 1349–1360 (2001)

    CAS  Article  Google Scholar 

  10. Eijpe, M., Offenberg, H., Jessberger, R., Revenkova, E. & Heyting, C. Meiotic cohesin REC8 marks the axial elements of rat synaptonemal complexes before cohesins SMC1β and SMC3. J. Cell Biol. 160, 657–670 (2003)

    CAS  Article  Google Scholar 

  11. Stoop-Myer, C. & Amon, A. Meiosis: Rec8 is the reason for cohesion. Nature Cell Biol. 1, E125–E127 (1999)

    CAS  Article  Google Scholar 

  12. Buonomo, S. B. et al. Disjunction of homologous chromosomes in meiosis I depends on proteolytic cleavage of the meiotic cohesin Rec8 by separin. Cell 103, 387–398 (2000)

    CAS  Article  Google Scholar 

  13. Kitajima, T. S., Miyazaki, Y., Yamamoto, M. & Watanabe, Y. Rec8 cleavage by separase is required for meiotic nuclear divisions in fission yeast. EMBO J. 22, 5643–5653 (2003)

    CAS  Article  Google Scholar 

  14. Shonn, M. A., McCarroll, R. & Murray, A. W. Spo13 protects meiotic cohesin at centromeres in meiosis I. Genes Dev. 16, 1659–1671 (2002)

    CAS  Article  Google Scholar 

  15. Lee, B. H., Amon, A. & Prinz, S. Spo13 regulates cohesin cleavage. Genes Dev. 16, 1672–1681 (2002)

    CAS  Article  Google Scholar 

  16. Blower, M. D. & Karpen, G. H. The role of Drosophila CID in kinetochore formation, cell-cycle progression and heterochromatin interactions. Nature Cell Biol. 3, 730–739 (2001)

    CAS  Article  Google Scholar 

  17. Kerrebrock, A. W., Moore, D. P., Wu, J. S. & Orr-Weaver, T. L. MEI-S332, a Drosophila protein required for sister-chromatid cohesion, can localize to meiotic centromere regions. Cell 83, 247–256 (1995)

    CAS  Article  Google Scholar 

  18. Kitajima, T. S., Yokobayashi, S., Yamamoto, M. & Watanabe, Y. Distinct cohesin complexes organize meiotic chromosome domains. Science 300, 1152–1155 (2003)

    ADS  CAS  Article  Google Scholar 

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

    CAS  Article  Google Scholar 

  20. Yokobayashi, S., Yamamoto, M. & Watanabe, Y. Cohesins determine the attachment manner of kinetochores to spindle microtubules at meiosis I in fission yeast. Mol. Cell. Biol. 23, 3965–3973 (2003)

    CAS  Article  Google Scholar 

  21. Yamamoto, A. & Hiraoka, Y. Monopolar spindle attachment of sister chromatids is ensured by two distinct mechanisms at the first meiotic division in fission yeast. EMBO J. 22, 2284–2296 (2003)

    CAS  Article  Google Scholar 

  22. Mata, J., Lyne, R., Burns, G. & Bähler, J. The transcriptional program of meiosis and sporulation in fission yeast. Nature Genet. 32, 143–147 (2002)

    CAS  Article  Google Scholar 

  23. Watanabe, Y., Yokobayashi, S., Yamamoto, M. & Nurse, P. Pre-meiotic S phase is linked to reductional chromosome segregation and recombination. Nature 409, 359–363 (2001)

    ADS  CAS  Article  Google Scholar 

  24. Saitoh, S., Takahashi, K. & Yanagida, M. Mis6, a fission yeast inner centromere protein, acts during G1/S and forms specialized chromatin required for equal segregation. Cell 90, 131–143 (1997)

    CAS  Article  Google Scholar 

  25. Ekwall, K. et al. The chromodomain protein Swi6: a key component at fission yeast centromeres. Science 269, 1429–1431 (1995)

    ADS  CAS  Article  Google Scholar 

  26. Bernard, P., Maure, J. F. & Javerzat, J. P. Fission yeast Bub1 is essential in setting up the meiotic pattern of chromosome segregation. Nature Cell Biol. 3, 522–526 (2001)

    CAS  Article  Google Scholar 

  27. Yamaguchi, S., Decottignies, A. & Nurse, P. Function of Cdc2p-dependent Bub1p phosphorylation and Bub1p kinase activity in the mitotic and meiotic spindle checkpoint. EMBO J. 22, 1075–1087 (2003)

    CAS  Article  Google Scholar 

  28. Bernard, P., Hardwick, K. & Javerzat, J. P. Fission yeast bub1 is a mitotic centromere protein essential for the spindle checkpoint and the preservation of correct ploidy through mitosis. J. Cell Biol. 143, 1775–1787 (1998)

    CAS  Article  Google Scholar 

  29. Henikoff, S., Pietrokovski, S. & Henikoff, J. G. Superior performance in protein homology detection with the Blocks Database servers. Nucleic Acids Res. 26, 309–312 (1998)

    CAS  Article  Google Scholar 

  30. Bailey, T. L. & Gribskov, M. Combining evidence using p-values: application to sequence homology searches. Bioinformatics 14, 48–54 (1998)

    CAS  Article  Google Scholar 

  31. Tang, T. T., Bickel, S. E., Young, L. M. & Orr-Weaver, T. L. Maintenance of sister-chromatid cohesion at the centromere by the Drosophila MEI-S322 protein. Genes Dev. 12, 3843–3856 (1998)

    CAS  Article  Google Scholar 

  32. Kumada, K. et al. Cut1 is loaded onto the spindle by binding to Cut2 and promotes anaphase spindle movement upon Cut2 proteolysis. Curr. Biol. 8, 633–641 (1998)

    CAS  Article  Google Scholar 

  33. LeBlanc, H. N., Tang, T. T., Wu, J. S. & Orr-Weaver, T. L. The mitotic centromeric protein MEI-S332 and its role in sister-chromatid cohesion. Chromosoma 108, 401–411 (1999)

    CAS  Article  Google Scholar 

  34. Bernard, P. et al. Requirement of heterochromatin for cohesion at centromeres. Science 294, 2539–2542 (2001)

    ADS  CAS  Article  Google Scholar 

  35. Nonaka, N. et al. Recruitment of cohesin to heterochromatic regions by Swi6/HP1 in fission yeast. Nature Cell Biol. 4, 89–93 (2002)

    CAS  Article  Google Scholar 

  36. Cahill, D. P. et al. Mutations of mitotic checkpoint genes in human cancers. Nature 392, 300–303 (1998)

    ADS  CAS  Article  Google Scholar 

  37. Scanlan, M. J. et al. Humoral immunity to human breast cancer: antigen definition and quantitative analysis of mRNA expression. Cancer Immun. 1, 4 (2001)

    CAS  PubMed  Google Scholar 

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

    CAS  Article  Google Scholar 

  39. Bähler, J. et al. Heterologous modules for efficient and versatile PCR-based gene targeting in Schizosaccharomyces pombe. Yeast 14, 943–951 (1998)

    Article  Google Scholar 

  40. Rao, H., Uhlmann, F., Nasmyth, K. & Varshavsky, A. Degradation of a cohesin subunit by the N-end rule pathway is essential for chromosome stability. Nature 410, 955–959 (2001)

    ADS  CAS  Article  Google Scholar 

  41. Longtine, M. S. et al. Additional modules for versatile and economical PCR-based gene deletion and modification in Saccharomyces cerevisiae. Yeast 14, 953–961 (1998)

    CAS  Article  Google Scholar 

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

    CAS  Article  Google Scholar 

  43. Glynn, J. M., Lustig, R. J., Berlin, A. & Chang, F. Role of bud6p and tea1p in the interaction between actin and microtubules for the establishment of cell polarity in fission yeast. Curr. Biol. 11, 836–845 (2001)

    CAS  Article  Google Scholar 

  44. Lupas, A., Van Dyke, M. & Stock, J. Predicting coiled coils from protein sequences. Science 252, 1162–1164 (1991)

    ADS  CAS  Article  Google Scholar 

Download references

Acknowledgements

We thank J. P. Cooper for critical reading of the manuscript; S. Hauf, M. Ohsugi and R. Watanabe for suggestions; J. P. Javerzat, F. Chang, T. Toda, M. Yanagida and P. Nurse for strains and plasmids of fission yeast; and F. Klein, K. P. Rabitsch, K. Nasmyth, M. Longtine, A. Shinohara and T. Maeda for strains and methods of budding yeast. We appreciate the support of M. Yamamoto and all members of his laboratory for their help. This work was supported in part by grants from the Ministry of Education, Science and Culture of Japan.

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Correspondence to Yoshinori Watanabe.

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Kitajima, T., Kawashima, S. & Watanabe, Y. The conserved kinetochore protein shugoshin protects centromeric cohesion during meiosis. Nature 427, 510–517 (2004). https://doi.org/10.1038/nature02312

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