title: Dictyostelium Sun-1 connects the centrosome to chromatin and ensures genome stability.
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.
authors.affiliation: Center for Biochemistry I, Medical Faculty, University of Cologne, Joseph-Stelzmann-Strasse 52, 50931 Cologne, Germany.
authors.forename: Huajiang
authors.initials: H
authors.lastname: Xiong
authors.forename: Francisco
authors.initials: F
authors.lastname: Rivero
authors.forename: Ursula
authors.initials: U
authors.lastname: Euteneuer
authors.forename: Subhanjan
authors.initials: S
authors.lastname: Mondal
authors.forename: Sebastian
authors.initials: S
authors.lastname: Mana-Capelli
authors.forename: Denis
authors.initials: D
authors.lastname: Larochelle
authors.forename: Annette
authors.initials: A
authors.lastname: Vogel
authors.forename: Berthold
authors.initials: B
authors.lastname: Gassen
authors.forename: Angelika A
authors.initials: AA
authors.lastname: Noegel
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D018385:Centrosome / Q000378:metabolism*; D002843:Chromatin / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D004023:Dictyostelium / Q000166:cytology / Q000235:genetics* / Q000378:metabolism; D042822:Genomic Instability; D008969:Molecular Sequence Data; D009685:Nuclear Envelope / Q000378:metabolism; D009687:Nuclear Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D020836:Protein Structure, Quaternary; D015800:Protozoan Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D002843:Chromatin; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D015800:Protozoan Proteins; D011993:Recombinant Fusion Proteins