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A conserved Mis12 centromere complex is linked to heterochromatic HP1 and outer kinetochore protein Zwint-1

Nature Cell Biology volume 6, pages 1135–1141 (2004)Cite this article

Abstract

Defects in kinetochore proteins often lead to aneuploidy and cancer. Mis12–Mtw1 is a conserved, essential kinetochore protein family. Here, we show that a Mis12 core complex exists in Schizosaccharomyces pombe and human cells. Nine polypeptides bind to human hMis12; two of these, HEC1 and Zwint-1, are authentic kinetochore proteins. Four other human proteins of unknown function (c20orf172, DC8, PMF1 and KIAA1570) correspond to yeast Mis12–Mtw1 complex components and are shown to be required for chromosome segregation in HeLa cells using RNA interference (RNAi). Surprisingly, hMis12 also forms a stable complex with the centromeric heterochromatin components HP1α and HP1γ. Double HP1 RNAi abolishes kinetochore localization of hMis12 and DC8. Therefore, centromeric HP1 may be the base to anchor the hMis12 core complex that is enriched with coiled coils and extends to outer Zwint-1 during mitosis.

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Figure 1: S. pombe proteins that interact with spMis12.
Figure 2: Human hMis12-binding proteins are located in the kinetochore or heterochromatin.
Figure 3: Interactions of the hMis12-containing complex with HP1.
Figure 4: Single RNAi of c20orf172 and double RNAi of HP1α and HP1γ.

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Acknowledgements

We are grateful to Y.-I. Nabeshima and A. Imura for immunopurification with the anti-GFP antibody; K. Yoda for anti-CENP-C and anti-CENP-A antibodies; and H. Saya for a Hela cell line. This work was supported by grants (Specially Promoted COE Research to M.Y. and Scientific Research to C.O.) from the Ministry of Education, Culture, Sports, Science and Technology of Japan. T.K., Y.T. and G.G. acknowledge Fellowships from the Japan Science Promotion Society (JSPS).

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Author notes

  1. Gohta Goshima

    Present address: Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94107, USA

  2. Chikashi Obuse and Osamu Iwasaki: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Gene Mechanisms, Graduate School of Biostudies, Kyoto University, Yoshida-Honmachi, Sakyo-ku, 606-8501, Kyoto, Japan

    Chikashi Obuse, Osamu Iwasaki, Tomomi Kiyomitsu, Gohta Goshima, Yusuke Toyoda & Mitsuhiro Yanagida

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Correspondence to Mitsuhiro Yanagida.

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Obuse, C., Iwasaki, O., Kiyomitsu, T. et al. A conserved Mis12 centromere complex is linked to heterochromatic HP1 and outer kinetochore protein Zwint-1. Nat Cell Biol 6, 1135–1141 (2004). https://doi.org/10.1038/ncb1187

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