title: The CENP-H-I complex is required for the efficient incorporation of newly synthesized CENP-A into centromeres.
abstract: In vertebrates, centromeres lack defined sequences and are thought to be propagated by epigenetic mechanisms involving the incorporation of specialized nucleosomes containing the histone H3 variant centromere protein (CENP)-A. However, the precise mechanisms that target CENP-A to centromeres remain poorly understood. Here, we isolated a multi-subunit complex, which includes the established inner kinetochore components CENP-H and CENP-I, and nine other proteins, from both human and chicken cells. Our analysis of these proteins demonstrates that the CENP-H-I complex can be divided into three functional sub-complexes, each of which is required for faithful chromosome segregation. Interestingly, newly expressed CENP-A is not efficiently incorporated into centromeres in knockout mutants of a subclass of CENP-H-I complex proteins, indicating that the CENP-H-I complex may function, in part, as a marker directing CENP-A deposition to centromeres.
authors.affiliation: Department of Molecular Genetics, National Institute of Genetics and The Graduate University for Advanced Studies, Mishima, Shizuoka 411-8540, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Okada
authors.forename: Iain M
authors.initials: IM
authors.lastname: Cheeseman
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Hori
authors.forename: Katsuya
authors.initials: K
authors.lastname: Okawa
authors.forename: Ian X
authors.initials: IX
authors.lastname: McLeod
authors.forename: John R
authors.initials: JR
authors.lastname: Yates
authors.forename: Arshad
authors.initials: A
authors.lastname: Desai
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Fukagawa
mesh_terms: D000818:Animals; D001324:Autoantigens / Q000096:biosynthesis* / Q000378:metabolism*; D002453:Cell Cycle; D002478:Cells, Cultured; D002503:Centromere / Q000737:chemistry / Q000378:metabolism*; D000076247:Centromere Protein A; D002645:Chickens; D002868:Chromosomal Proteins, Non-Histone / Q000096:biosynthesis* / Q000378:metabolism*; D020090:Chromosome Segregation / Q000235:genetics; D003598:Cytoskeletal Proteins; D004268:DNA-Binding Proteins / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D008954:Models, Biological; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D009687:Nuclear Proteins / Q000378:metabolism; D011485:Protein Binding; D021381:Protein Transport
chemical_list: D001324:Autoantigens; C000619700:CENPA protein, human; C121933:CENPH protein, human; C484297:CENPI protein, human; D000076247:Centromere Protein A; D002868:Chromosomal Proteins, Non-Histone; D003598:Cytoskeletal Proteins; D004268:DNA-Binding Proteins; C120529:NDC80 protein, human; D009687:Nuclear Proteins