Dictyostelium Sun-1 Connects the Centrosome to Chromatin and Ensures Genome Stability

Authors

  • Huajiang Xiong,

    1. Center for Biochemistry I, Medical Faculty, University of Cologne, Joseph-Stelzmann-Strasse 52, 50931 Cologne, Germany
    2. Center for Molecular Medicine Cologne (CMMC), University of Cologne, Joseph-Stelzmann-Strasse 52, 50931 Cologne, Germany
    3. Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Joseph-Stelzmann-Strasse 52, 50931 Cologne, Germany
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  • Francisco Rivero,

    1. Center for Biochemistry I, Medical Faculty, University of Cologne, Joseph-Stelzmann-Strasse 52, 50931 Cologne, Germany
    2. Center for Molecular Medicine Cologne (CMMC), University of Cologne, Joseph-Stelzmann-Strasse 52, 50931 Cologne, Germany
    3. Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Joseph-Stelzmann-Strasse 52, 50931 Cologne, Germany
    4. Current address: The Hull York Medical School, University of Hull, HU6 7RX Hull, UK
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  • Ursula Euteneuer,

    1. Institute for Cell Biology and Munich Center for Integrated Protein Science (CIPSM), University of Munich, Schillerstrasse 42, 80336 Munich, Germany
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  • Subhanjan Mondal,

    1. Center for Biochemistry I, Medical Faculty, University of Cologne, Joseph-Stelzmann-Strasse 52, 50931 Cologne, Germany
    2. Center for Molecular Medicine Cologne (CMMC), University of Cologne, Joseph-Stelzmann-Strasse 52, 50931 Cologne, Germany
    3. Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Joseph-Stelzmann-Strasse 52, 50931 Cologne, Germany
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  • Sebastian Mana-Capelli,

    1. Department of Biology, Clark University, 950 Main Street, Worcester, MA 01610, USA
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  • Denis Larochelle,

    1. Department of Biology, Clark University, 950 Main Street, Worcester, MA 01610, USA
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  • Annette Vogel,

    1. Institute for Cell Biology and Munich Center for Integrated Protein Science (CIPSM), University of Munich, Schillerstrasse 42, 80336 Munich, Germany
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  • Berthold Gassen,

    1. Center for Biochemistry I, Medical Faculty, University of Cologne, Joseph-Stelzmann-Strasse 52, 50931 Cologne, Germany
    2. Center for Molecular Medicine Cologne (CMMC), University of Cologne, Joseph-Stelzmann-Strasse 52, 50931 Cologne, Germany
    3. Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Joseph-Stelzmann-Strasse 52, 50931 Cologne, Germany
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  • Angelika A. Noegel

    Corresponding author
    1. Center for Biochemistry I, Medical Faculty, University of Cologne, Joseph-Stelzmann-Strasse 52, 50931 Cologne, Germany
    2. Center for Molecular Medicine Cologne (CMMC), University of Cologne, Joseph-Stelzmann-Strasse 52, 50931 Cologne, Germany
    3. Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Joseph-Stelzmann-Strasse 52, 50931 Cologne, Germany
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*Angelika A. Noegel, noegel@uni-koeln.de

Abstract

The centrosome-nucleus attachment is a prerequisite for faithful chromosome segregation during mitosis. We addressed the function of the nuclear envelope (NE) protein Sun-1 in centrosome-nucleus connection and the maintenance of genome stability in Dictyostelium discoideum. We provide evidence that Sun-1 requires direct chromatin binding for its inner nuclear membrane targeting. Truncation of the cryptic N-terminal chromatin-binding domain of Sun-1 induces dramatic separation of the inner from the outer nuclear membrane and deformations in nuclear morphology, which are also observed using a Sun-1 RNAi construct. Thus, chromatin binding of Sun-1 defines the integrity of the nuclear architecture. In addition to its role as a NE scaffold, we find that abrogation of the chromatin binding of Sun-1 dissociates the centrosome-nucleus connection, demonstrating that Sun-1 provides an essential link between the chromatin and the centrosome. Moreover, loss of the centrosome-nucleus connection causes severe centrosome hyperamplification and defective spindle formation, which enhances aneuploidy and cell death significantly. We highlight an important new aspect for Sun-1 in coupling the centrosome and nuclear division during mitosis to ensure faithful chromosome segregation.

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