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Shugoshin collaborates with protein phosphatase 2A to protect cohesin

Nature volume 441, pages 4652 (04 May 2006) | Download Citation

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Abstract

Sister chromatid cohesion, mediated by a complex called cohesin, is crucial—particularly at centromeres—for proper chromosome segregation in mitosis and meiosis. In animal mitotic cells, phosphorylation of cohesin promotes its dissociation from chromosomes, but centromeric cohesin is protected by shugoshin until kinetochores are properly captured by the spindle microtubules. However, the mechanism of shugoshin-dependent protection of cohesin is unknown. Here we find a specific subtype of serine/threonine protein phosphatase 2A (PP2A) associating with human shugoshin. PP2A colocalizes with shugoshin at centromeres and is required for centromeric protection. Purified shugoshin complex has an ability to reverse the phosphorylation of cohesin in vitro, suggesting that dephosphorylation of cohesin is the mechanism of protection at centromeres. Meiotic shugoshin of fission yeast also associates with PP2A, with both proteins collaboratively protecting Rec8-containing cohesin at centromeres. Thus, we have revealed a conserved mechanism of centromeric protection of eukaryotic chromosomes in mitosis and meiosis.

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Acknowledgements

We thank S. Hauf for critically reading the manuscript. We also thank B. Akiyoshi for yeast two-hybrid screening of S. pombe Sgo1; K. Nasmyth for communicating unpublished results; J. M. Peters, E. Nishida, F. Ishikawa, Y. Nakatani, M. Sato and T. Toda for reagents; J. M. Peters, M. Ohsugi and M. Shimura for methods; and all members in our laboratory for their valuable discussion and help. K.I. was supported by a JSPS fellowship. This work was supported in part by the New Energy and Industrial Technology Development Organization (to T.N.), and by the Toray Science Foundation, Uehara Memorial 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.). Author Contributions Experiments in Figs 13 were mainly performed by T.S.K., Fig. 4 by K.I., and Figs 5 and 6 by T.S. and S.A.K. Mass spectrometry of hSgo1 immunoprecipitates was performed by S.I. and T.N. Experimental design, interpretation of data, and the preparation of the manuscript were mainly conducted by T.S.K., T.S., K.I. and Y.W.

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Affiliations

  1. Laboratory of Chromosome Dynamics, Institute of Molecular and Cellular Biosciences,

    • Tomoya S. Kitajima
    • , Takeshi Sakuno
    • , Kei-ichiro Ishiguro
    • , Shigehiro A. Kawashima
    •  & Yoshinori Watanabe
  2. Graduate Program in Biophysics and Biochemistry, University of Tokyo, and

    • Shigehiro A. Kawashima
    •  & Yoshinori Watanabe
  3. SORST, Japan Science and Technology Agency, Yayoi, Tokyo 113-0032, Japan

    • Takeshi Sakuno
    •  & Yoshinori Watanabe
  4. National Institute of Advanced Industrial Science and Technology, Biological Information Research Center, Aomi, Tokyo 135-0064, Japan

    • Shun-ichiro Iemura
    •  & Tohru Natsume

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Reprints and permissions information is available at npg.nature.com/reprintsandpermissions. The authors declare no competing financial interests.

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Correspondence to Yoshinori Watanabe.

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    This file contains Supplementary Table 1, Supplementary Figures 1–9, Supplementary Methods and additional references.

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https://doi.org/10.1038/nature04663

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