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Unified mode of centromeric protection by shugoshin in mammalian oocytes and somatic cells

Nature Cell Biology volume 10, pages 42–52 (2008)Cite this article

Abstract

Reductional chromosome segregation in germ cells, where sister chromatids are pulled to the same pole, accompanies the protection of cohesin at centromeres from separase cleavage. Here, we show that mammalian shugoshin Sgo2 is expressed in germ cells and is solely responsible for the centromeric localization of PP2A and the protection of cohesin Rec8 in oocytes, proving conservation of the mechanism from yeast to mammals. However, this role of Sgo2 contrasts with its mitotic role in protecting centromeric cohesin only from prophase dissociation, but never from anaphase cleavage. We demonstrate that, in somatic cells, shugoshin colocalizes with cohesin in prophase or prometaphase, but their localizations become separate when centromeres are pulled oppositely at metaphase. Remarkably, if tension is artificially removed from the centromeres at the metaphase–anaphase transition, cohesin at the centromeres can be protected from separase cleavage even in somatic cells, as in germ cells. These results argue for a unified view of centromeric protection by shugoshin in mitosis and meiosis.

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Figure 1: Sgo2 is highly expressed in germ cells.
Figure 2: Sgo2, but not Sgo1, is required for the protection of centromeric cohesion in oocytes.
Figure 3: Inter-centromeric localization of Sgo2 and Rec8 at metaphase I and metaphase II in oocytes.
Figure 4: Sgo2 relocates towards kinetochores during metaphase II.
Figure 5: Shugoshins relocate towards kinetochores during mitotic metaphase.
Figure 6: The tension on bi-oriented mitotic chromosomes displaces shugoshins from cohesin sites within the centromeres.
Figure 7: Cohesin can be protected at the centromeres from separase cleavage, even in somatic cells if tension does not act on the centromeres.
Figure 8: Schematic representation of a unified view of centromeric protection of cohesin in mitosis and meiosis.

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Acknowledgements

We thank: S. Hauf for critical reading of the manuscript; T. Hirota for personal communication; S. S. Taylor for the anti-mBub1 antibody; H. Suzuki for the anti-hSgo1 13G1 antibody; T. Hirano for the anti-Wapl antibody; and J.-M. Peters for Myc–Rad21-expressing HeLa cells. This work was supported in part by: a Grant-in-Aid for Scientific Research from the Japan Society for the Promotion of Science to J.L. and T.S.K.; by 21st Century COE Programs to J.L., T. Miyano and M.M.; by Ground-based Research Program for Space Utilization from Japan Space Forum to K.Y. and T. Morita; and by the Toray Science Foundation and a Grant-in-Aid for Specially Promoted Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan to Y.W.

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  1. Jibak Lee and Tomoya S. Kitajima: These authors contributed equally to this work.

Authors and Affiliations

  1. Laboratory of Reproductive Biology and Biotechnology, Graduate School of Science and Technology, Kobe University, Kobe, 657-8501, Japan

    Jibak Lee, Takashi Miyano & Masashi Miyake

  2. Laboratory of Chromosome Dynamics, Institute of Molecular and Cellular Biosciences, University of Tokyo, Yayoi, 113-0032, Tokyo, Japan

    Tomoya S. Kitajima, Yuji Tanno & Yoshinori Watanabe

  3. Department of Molecular Genetics, Graduate School of Medicine, Osaka City University, Asahimachi, Abeno, 545-8585, Osaka, Japan

    Kayo Yoshida & Takashi Morita

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Correspondence to Yoshinori Watanabe.

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Lee, J., Kitajima, T., Tanno, Y. et al. Unified mode of centromeric protection by shugoshin in mammalian oocytes and somatic cells. Nat Cell Biol 10, 42–52 (2008). https://doi.org/10.1038/ncb1667

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