title: Ectopic centromere nucleation by CENP--a in fission yeast.
abstract: The centromere is a specific chromosomal locus that organizes the assembly of the kinetochore. It plays a fundamental role in accurate chromosome segregation. In most eukaryotic organisms, each chromosome contains a single centromere the position and function of which are epigenetically specified. Occasionally, centromeres form at ectopic loci, which can be detrimental to the cell. However, the mechanisms that protect the cell against ectopic centromeres (neocentromeres) remain poorly understood. Centromere protein-A (CENP-A), a centromere-specific histone 3 (H3) variant, is found in all centromeres and is indispensable for centromere function. Here we report that the overexpression of CENP-A(Cnp1) in fission yeast results in the assembly of CENP-A(Cnp1) at noncentromeric chromatin during mitosis and meiosis. The noncentromeric CENP-A preferentially assembles near heterochromatin and is capable of recruiting kinetochore components. Consistent with this, cells overexpressing CENP-A(Cnp1) exhibit severe chromosome missegregation and spindle microtubule disorganization. In addition, pulse induction of CENP-A(Cnp1) overexpression reveals that ectopic CENP-A chromatin can persist for multiple generations. Intriguingly, ectopic assembly of CENP-A(cnp1) is suppressed by overexpression of histone H3 or H4. Finally, we demonstrate that deletion of the N-terminal domain of CENP-A(cnp1) results in an increase in the number of ectopic CENP-A sites and provide evidence that the N-terminal domain of CENP-A prevents CENP-A assembly at ectopic loci via the ubiquitin-dependent proteolysis. These studies expand our current understanding of how noncentromeric chromatin is protected from mistakenly assembling CENP-A.
authors.affiliation: Department of Biology, New York University, New York, New York 10003.
authors.forename: Marlyn
authors.initials: M
authors.lastname: Gonzalez
authors.affiliation: Department of Biology, New York University, New York, New York 10003.
authors.forename: Haijin
authors.initials: H
authors.lastname: He
authors.affiliation: Department of Biology, New York University, New York, New York 10003.
authors.forename: Qianhua
authors.initials: Q
authors.lastname: Dong
authors.affiliation: Department of Biology, New York University, New York, New York 10003.
authors.forename: Siyu
authors.initials: S
authors.lastname: Sun
authors.affiliation: Department of Biology, New York University, New York, New York 10003 fl43@nyu.edu.
authors.forename: Fei
authors.initials: F
authors.lastname: Li
mesh_terms: D001324:Autoantigens / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism; D002503:Centromere / Q000235:genetics* / Q000378:metabolism*; D000076247:Centromere Protein A; D042002:Chromatin Assembly and Disassembly; D002868:Chromosomal Proteins, Non-Histone / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D020090:Chromosome Segregation; D015870:Gene Expression; D017930:Genes, Reporter; D006570:Heterochromatin / Q000235:genetics / Q000378:metabolism; D006657:Histones / Q000235:genetics / Q000378:metabolism; D018386:Kinetochores / Q000378:metabolism; D008540:Meiosis; D008938:Mitosis; D054730:Protein Interaction Domains and Motifs; D059748:Proteolysis; D012568:Schizosaccharomyces / Q000235:genetics* / Q000378:metabolism*; D008941:Spindle Apparatus / Q000378:metabolism; D025801:Ubiquitin / Q000378:metabolism
chemical_list: D001324:Autoantigens; D000076247:Centromere Protein A; D002868:Chromosomal Proteins, Non-Histone; D006570:Heterochromatin; D006657:Histones; D025801:Ubiquitin
keywords: CENP-A; centromere; epigenetics; heterochromatin; neocentromere