RRC ID 31366
著者 Gonzalez M, He H, Dong Q, Sun S, Li F.
タイトル Ectopic centromere nucleation by CENP--a in fission yeast.
ジャーナル Genetics
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.
巻・号 198(4)
ページ 1433-46
公開日 2014-12-1
DOI 10.1534/genetics.114.171173
PII genetics.114.171173
PMID 25298518
PMC PMC4256763
MeSH Autoantigens / chemistry Autoantigens / genetics* Autoantigens / metabolism* Cell Nucleus / genetics Cell Nucleus / metabolism Centromere / genetics* Centromere / metabolism* Centromere Protein A Chromatin Assembly and Disassembly Chromosomal Proteins, Non-Histone / chemistry Chromosomal Proteins, Non-Histone / genetics* Chromosomal Proteins, Non-Histone / metabolism* Chromosome Segregation Gene Expression Genes, Reporter Heterochromatin / genetics Heterochromatin / metabolism Histones / genetics Histones / metabolism Kinetochores / metabolism Meiosis Mitosis Protein Interaction Domains and Motifs Proteolysis Schizosaccharomyces / genetics* Schizosaccharomyces / metabolism* Spindle Apparatus / metabolism Ubiquitin / metabolism
IF 4.015
引用数 26
WOS 分野 GENETICS & HEREDITY
リソース情報
酵母 S. bombe strains