title: Licensing of Centromeric Chromatin Assembly through the Mis18α-Mis18β Heterotetramer.
abstract: Centromeres are specialized chromatin domains specified by the centromere-specific CENP-A nucleosome. The stable inheritance of vertebrate centromeres is an epigenetic process requiring deposition of new CENP-A nucleosomes by HJURP. We show HJURP is recruited to centromeres through a direct interaction between the HJURP centromere targeting domain and the Mis18α-β C-terminal coiled-coil domains. We demonstrate Mis18α and Mis18β form a heterotetramer through their C-terminal coiled-coil domains. Mis18α-β heterotetramer formation is required for Mis18BP1 binding and centromere recognition. S. pombe contains a single Mis18 isoform that forms a homotetramer, showing tetrameric Mis18 is conserved from fission yeast to humans. HJURP binding disrupts the Mis18α-β heterotetramer and removes Mis18α from centromeres. We propose stable binding of Mis18 to centromeres in telophase licenses them for CENP-A deposition. Binding of HJURP deposits CENP-A at centromeres and facilitates the removal of Mis18, restricting CENP-A deposition to a single event per cell cycle.
authors.affiliation: Department of Biochemistry and Molecular Genetics, University of Virginia Medical School, Charlottesville, VA 22908, USA.
authors.forename: Isaac K
authors.initials: IK
authors.lastname: Nardi
authors.affiliation: Department of Biochemistry and Molecular Genetics, University of Virginia Medical School, Charlottesville, VA 22908, USA.
authors.forename: Ewelina
authors.initials: E
authors.lastname: Zasadzińska
authors.affiliation: Department of Biochemistry and Molecular Genetics, University of Virginia Medical School, Charlottesville, VA 22908, USA.
authors.forename: Madison E
authors.initials: ME
authors.lastname: Stellfox
authors.affiliation: Department of Biochemistry and Molecular Genetics, University of Virginia Medical School, Charlottesville, VA 22908, USA.
authors.forename: Christina M
authors.initials: CM
authors.lastname: Knippler
authors.affiliation: Department of Biochemistry and Molecular Genetics, University of Virginia Medical School, Charlottesville, VA 22908, USA; Department of Biochemistry and Molecular Genetics, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA; Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, 320 E. Superior Street, Chicago, IL 60611, USA. Electronic address: dfoltz@northwestern.edu.
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Foltz
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000595:Amino Acid Sequence; D001324:Autoantigens / Q000235:genetics / Q000378:metabolism; D018797:Cell Cycle Proteins; D045744:Cell Line, Tumor; D002503:Centromere / Q000378:metabolism*; D000076247:Centromere Protein A; D042002:Chromatin Assembly and Disassembly; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008969:Molecular Sequence Data; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D055503:Protein Multimerization; D015398:Signal Transduction; D013692:Telophase; D014162:Transfection
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D001324:Autoantigens; C000619700:CENPA protein, human; D018797:Cell Cycle Proteins; D000076247:Centromere Protein A; D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; C524371:HJURP protein, human; C502942:MIS18A protein, human; C517146:OIP5 protein, human
keywords: centromere; chromatin; mitosis; nucleosome