title: Epigenetic inactivation and subsequent heterochromatinization of a centromere stabilize dicentric chromosomes.
abstract: BACKGROUND
  The kinetochore is a multiprotein complex that forms on a chromosomal locus designated as the centromere, which links the chromosome to the spindle during mitosis and meiosis. Most eukaryotes, with the exception of holocentric species, have a single distinct centromere per chromosome, and the presence of multiple centromeres on a single chromosome is predicted to cause breakage and/or loss of that chromosome. However, some stably maintained non-Robertsonian translocated chromosomes have been reported, suggesting that the excessive centromeres are inactivated by an as yet undetermined mechanism.
  
  
  RESULTS
  We have developed systems to generate dicentric chromosomes containing two centromeres by fusing two chromosomes in fission yeast. Although the majority of cells harboring the artificial dicentric chromosome are arrested with elongated cell morphology in a manner dependent on the DNA structure checkpoint genes, a portion of the cells survive by converting the dicentric chromosome into a stable functional monocentric chromosome; either centromere was inactivated epigenetically or by DNA rearrangement. Mutations compromising kinetochore formation increased the frequency of epigenetic centromere inactivation. The inactivated centromere is occupied by heterochromatin and frequently reactivated in heterochromatin- or histone deacetylase-deficient mutants.
  
  
  CONCLUSIONS
  Chromosomes with multiple centromeres are stabilized by epigenetic centromere inactivation, which is initiated by kinetochore disassembly. Consequent heterochromatinization and histone deacetylation expanding from pericentric repeats to the central domain prevent reactivation of the inactivated centromere.
authors.affiliation: Division of Cell Biology, Institute of Life Science, Kurume University, Hyakunen-kohen 1-1, Kurume, Fukuoka 839-0864, Japan. satou_hiroshi@kurume-u.ac.jp
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Sato
authors.forename: Fumie
authors.initials: F
authors.lastname: Masuda
authors.forename: Yuko
authors.initials: Y
authors.lastname: Takayama
authors.forename: Kohta
authors.initials: K
authors.lastname: Takahashi
authors.forename: Shigeaki
authors.initials: S
authors.lastname: Saitoh
mesh_terms: D000107:Acetylation; D059447:Cell Cycle Checkpoints / Q000235:genetics; D002503:Centromere; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000378:metabolism; D018244:Chromosomes, Artificial, Yeast; D015825:Chromosomes, Fungal; D004271:DNA, Fungal / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D044127:Epigenesis, Genetic; D006570:Heterochromatin / Q000235:genetics*; D006657:Histones / Q000378:metabolism; D007399:Interphase / Q000235:genetics; D018386:Kinetochores / Q000378:metabolism; D009154:Mutation; D012568:Schizosaccharomyces / Q000166:cytology / Q000235:genetics*; D029702:Schizosaccharomyces pombe Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D002868:Chromosomal Proteins, Non-Histone; C410349:Cnp1 protein, S pombe; D004271:DNA, Fungal; D006570:Heterochromatin; D006657:Histones; D029702:Schizosaccharomyces pombe Proteins; C526400:sir2 protein, S pombe