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Shugoshin collaborates with protein phosphatase 2A to protect cohesin


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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Figure 1: PP2A associates and colocalizes with hSgo1.
Figure 2: PP2A is required for centromeric protection.
Figure 3: Interdependency of shugoshin and PP2A for localization.
Figure 4: Dephosphorylation of cohesin subunit SA.
Figure 5: S. pombe PP2A associating with Sgo1 is required for centromeric protection of Rec8-containing cohesin during meiosis I.
Figure 6: Individual ability of PP2A and shugoshin for centromeric protection.

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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 We also thank B. Akiyoshi for yeast two-hybrid screening of S. pombe Sgo1; K. Nasmyth for communicating unpublished results; J. M. Peters, E. Nishida, F. Ishikawa, Y. Nakatani, M. Sato and T. Toda for reagents; J. M. Peters, M. Ohsugi and M. Shimura for methods; and all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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Correspondence to Yoshinori Watanabe.

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Kitajima, T., Sakuno, T., Ishiguro, Ki. et al. Shugoshin collaborates with protein phosphatase 2A to protect cohesin. Nature 441, 46–52 (2006).

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