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Microtubules and Alp7–Alp14 (TACC–TOG) reposition chromosomes before meiotic segregation

Nature Cell Biology volume 15, pages 786796 (2013) | Download Citation

Abstract

Tethering kinetochores at spindle poles facilitates their efficient capture and segregation by microtubules at mitotic onset in yeast. During meiotic prophase of fission yeast, however, kinetochores are detached from the poles, which facilitates meiotic recombination but may cause a risk of chromosome mis-segregation during meiosis. How cells circumvent this dilemma remains unclear. Here we show that an extensive microtubule array assembles from the poles at meiosis I onset and retrieves scattered kinetochores towards the poles to prevent chromosome drift. Moreover, the microtubule-associated protein complex Alp7–Alp14 (the fission yeast orthologues of mammalian TACC–TOG) is phosphorylated by Polo kinase, which promotes its meiosis-specific association to the outer kinetochore complex Nuf2–Ndc80 of scattered kinetochores, thereby assisting in capturing remote kinetochores. Although TOG was recently characterized as a microtubule polymerase, Dis1 (the other TOG orthologue in fission yeast), together with the Dam1 complex, plays a role in microtubule shortening to pull kinetochores polewards. Thus, microtubules and their binding proteins uniquely reconstitute chromosome configuration during meiosis.

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Acknowledgements

We thank F. Uhlmann for support; Y. Hiraoka, J. Cooper, M. Toya, K. Tanaka and N. H. Tang for discussion; and S. Sazer (Baylor College of Medicine, USA), Y. Watanabe (University of Tokyo, Japan), Y. Hiraoka (Osaka University, Japan) and H. Murakami (Chuo University, Japan) for materials. N.O. is a research fellow of JSPS. This work was supported by a Grant-in-Aid for Scientific Research on Priority Areas ‘Cell Proliferation Control’ from MEXT, by Grants-in-Aid for Young Scientists (A) and for Scientific Research (B) from JSPS, by the Naito Foundation (to M.S.), by Grants-in-Aid for Specially Promoted Research and for Scientific Research (S) from JSPS (to M.Y.), and by Cancer Research UK (to T.T.). This work was also supported in part by the Global COE Program, MEXT, Japan.

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Affiliations

  1. Department of Biophysics and Biochemistry, Graduate School of Science, University of Tokyo, 7-3-1 Hongo, Tokyo 113-0032, Japan

    • Yasutaka Kakui
    • , Masamitsu Sato
    • , Naoyuki Okada
    •  & Masayuki Yamamoto
  2. Chromosome Segregation Laboratory, Cancer Research UK, London Research Institute, 44 Lincoln’s Inn Fields, London WC2A 3LY, UK

    • Yasutaka Kakui
  3. PRESTO, Japan Science and Technology Agency, 4-1-8 Honcho, Kawagurchi, Saitama 332-0012, Japan

    • Masamitsu Sato
  4. Laboratory of Cytoskeletal Logistics, Department of Life Science and Medical Bioscience, Graduate School of Advanced Science and Engineering, Waseda University, 2-2 Wakamatsucho, Shinjuku, Tokyo 162-8480, Japan

    • Masamitsu Sato
  5. Cell Regulation Laboratory, Cancer Research UK, London Research Institute, 44 Lincoln’s Inn Fields, London WC2A 3LY, UK

    • Takashi Toda
  6. Kazusa DNA Research Institute, 2-6-7 Kazusa-kamatari, Kisarazu, Chiba 292-0818, Japan

    • Masayuki Yamamoto

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Contributions

The experiments were designed by Y.K. with support from M.S. and performed by Y.K., except for Figs 1c,d, 2a, 4b,e and Supplementary Fig. S2b (by M.S.), and 6b (by N.O.). M.S. wrote the manuscript with support from Y.K., T.T. and M.Y.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Masamitsu Sato.

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https://doi.org/10.1038/ncb2782

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