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Genetics. Nov 1999; 153(3): 1153–1169.
PMCID: PMC1460827

Fission yeast mutants that alleviate transcriptional silencing in centromeric flanking repeats and disrupt chromosome segregation.


In the fission yeast Schizosaccharomyces pombe genes are transcriptionally silenced when placed within centromeres, within or close to the silent mating-type loci or adjacent to telomeres. Factors required to maintain mating-type silencing also affect centromeric silencing and chromosome segregation. We isolated mutations that alleviate repression of marker genes in the inverted repeats flanking the central core of centromere I. Mutations csp1 to 13 (centromere: suppressor of position effect) defined 12 loci. Ten of the csp mutants have no effect on mat2/3 or telomere silencing. All csp mutants allow some expression of genes in the centromeric flanking repeat, but expression in the central core is undetectable. Consistent with defective centromere structure and function, chromosome loss rates are elevated in all csp mutants. Mutants csp1 to 6 are temperature-sensitive lethal and csp3 and csp6 cells are defective in mitosis at 36 degrees. csp7 to 13 display a high incidence of lagging chromosomes on late anaphase spindles. Thus, by screening for mutations that disrupt silencing in the flanking region of a fission yeast centromere a novel collection of mutants affecting centromere architecture and chromosome segregation has been isolated.

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Selected References

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  • Allshire RC, Javerzat JP, Redhead NJ, Cranston G. Position effect variegation at fission yeast centromeres. Cell. 1994 Jan 14;76(1):157–169. [PubMed]
  • Allshire RC, Nimmo ER, Ekwall K, Javerzat JP, Cranston G. Mutations derepressing silent centromeric domains in fission yeast disrupt chromosome segregation. Genes Dev. 1995 Jan 15;9(2):218–233. [PubMed]
  • Baksa K, Morawietz H, Dombrádi V, Axton M, Taubert H, Szabó G, Török I, Udvardy A, Gyurkovics H, Ször B, et al. Mutations in the protein phosphatase 1 gene at 87B can differentially affect suppression of position-effect variegation and mitosis in Drosophila melanogaster. Genetics. 1993 Sep;135(1):117–125. [PMC free article] [PubMed]
  • Baum M, Ngan VK, Clarke L. The centromeric K-type repeat and the central core are together sufficient to establish a functional Schizosaccharomyces pombe centromere. Mol Biol Cell. 1994 Jul;5(7):747–761. [PMC free article] [PubMed]
  • Beach DH, Klar AJ. Rearrangements of the transposable mating-type cassettes of fission yeast. EMBO J. 1984 Mar;3(3):603–610. [PMC free article] [PubMed]
  • Bernard P, Hardwick K, Javerzat JP. Fission yeast bub1 is a mitotic centromere protein essential for the spindle checkpoint and the preservation of correct ploidy through mitosis. J Cell Biol. 1998 Dec 28;143(7):1775–1787. [PMC free article] [PubMed]
  • Hahnenberger KM, Baum MP, Polizzi CM, Carbon J, Clarke L. Construction of functional artificial minichromosomes in the fission yeast Schizosaccharomyces pombe. Proc Natl Acad Sci U S A. 1989 Jan;86(2):577–581. [PMC free article] [PubMed]
  • Boeke JD, LaCroute F, Fink GR. A positive selection for mutants lacking orotidine-5'-phosphate decarboxylase activity in yeast: 5-fluoro-orotic acid resistance. Mol Gen Genet. 1984;197(2):345–346. [PubMed]
  • Boeke JD, Trueheart J, Natsoulis G, Fink GR. 5-Fluoroorotic acid as a selective agent in yeast molecular genetics. Methods Enzymol. 1987;154:164–175. [PubMed]
  • Harrington JJ, Van Bokkelen G, Mays RW, Gustashaw K, Willard HF. Formation of de novo centromeres and construction of first-generation human artificial microchromosomes. Nat Genet. 1997 Apr;15(4):345–355. [PubMed]
  • Bridge AJ, Morphew M, Bartlett R, Hagan IM. The fission yeast SPB component Cut12 links bipolar spindle formation to mitotic control. Genes Dev. 1998 Apr 1;12(7):927–942. [PMC free article] [PubMed]
  • Brown KE, Barnett MA, Burgtorf C, Shaw P, Buckle VJ, Brown WR. Dissecting the centromere of the human Y chromosome with cloned telomeric DNA. Hum Mol Genet. 1994 Aug;3(8):1227–1237. [PubMed]
  • Ikeno M, Grimes B, Okazaki T, Nakano M, Saitoh K, Hoshino H, McGill NI, Cooke H, Masumoto H. Construction of YAC-based mammalian artificial chromosomes. Nat Biotechnol. 1998 May;16(5):431–439. [PubMed]
  • Cahill DP, Lengauer C, Yu J, Riggins GJ, Willson JK, Markowitz SD, Kinzler KW, Vogelstein B. Mutations of mitotic checkpoint genes in human cancers. Nature. 1998 Mar 19;392(6673):300–303. [PubMed]
  • Ivanova AV, Bonaduce MJ, Ivanov SV, Klar AJ. The chromo and SET domains of the Clr4 protein are essential for silencing in fission yeast. Nat Genet. 1998 Jun;19(2):192–195. [PubMed]
  • Cavalli G, Paro R. Chromo-domain proteins: linking chromatin structure to epigenetic regulation. Curr Opin Cell Biol. 1998 Jun;10(3):354–360. [PubMed]
  • Javerzat JP, McGurk G, Cranston G, Barreau C, Bernard P, Gordon C, Allshire R. Defects in components of the proteasome enhance transcriptional silencing at fission yeast centromeres and impair chromosome segregation. Mol Cell Biol. 1999 Jul;19(7):5155–5165. [PMC free article] [PubMed]
  • Chikashige Y, Kinoshita N, Nakaseko Y, Matsumoto T, Murakami S, Niwa O, Yanagida M. Composite motifs and repeat symmetry in S. pombe centromeres: direct analysis by integration of NotI restriction sites. Cell. 1989 Jun 2;57(5):739–751. [PubMed]
  • Karpen GH. Position-effect variegation and the new biology of heterochromatin. Curr Opin Genet Dev. 1994 Apr;4(2):281–291. [PubMed]
  • Karpen GH, Allshire RC. The case for epigenetic effects on centromere identity and function. Trends Genet. 1997 Dec;13(12):489–496. [PubMed]
  • Cléard F, Delattre M, Spierer P. SU(VAR)3-7, a Drosophila heterochromatin-associated protein and companion of HP1 in the genomic silencing of position-effect variegation. EMBO J. 1997 Sep 1;16(17):5280–5288. [PMC free article] [PubMed]
  • Kilmartin JV. Purification of yeast tubulin by self-assembly in vitro. Biochemistry. 1981 Jun 9;20(12):3629–3633. [PubMed]
  • Edwards RJ, Carr AM. Analysis of radiation-sensitive mutants of fission yeast. Methods Enzymol. 1997;283:471–494. [PubMed]
  • Laurenson P, Rine J. Silencers, silencing, and heritable transcriptional states. Microbiol Rev. 1992 Dec;56(4):543–560. [PMC free article] [PubMed]
  • Lengauer C, Kinzler KW, Vogelstein B. Genetic instability in colorectal cancers. Nature. 1997 Apr 10;386(6625):623–627. [PubMed]
  • Lorentz A, Ostermann K, Fleck O, Schmidt H. Switching gene swi6, involved in repression of silent mating-type loci in fission yeast, encodes a homologue of chromatin-associated proteins from Drosophila and mammals. Gene. 1994 May 27;143(1):139–143. [PubMed]
  • Ekwall K, Ruusala T. Mutations in rik1, clr2, clr3 and clr4 genes asymmetrically derepress the silent mating-type loci in fission yeast. Genetics. 1994 Jan;136(1):53–64. [PMC free article] [PubMed]
  • Ekwall K, Javerzat JP, Lorentz A, Schmidt H, Cranston G, Allshire R. The chromodomain protein Swi6: a key component at fission yeast centromeres. Science. 1995 Sep 8;269(5229):1429–1431. [PubMed]
  • Ekwall K, Nimmo ER, Javerzat JP, Borgstrøm B, Egel R, Cranston G, Allshire R. Mutations in the fission yeast silencing factors clr4+ and rik1+ disrupt the localisation of the chromo domain protein Swi6p and impair centromere function. J Cell Sci. 1996 Nov;109(Pt 11):2637–2648. [PubMed]
  • Murakami S, Matsumoto T, Niwa O, Yanagida M. Structure of the fission yeast centromere cen3: direct analysis of the reiterated inverted region. Chromosoma. 1991 Dec;101(4):214–221. [PubMed]
  • Ekwall K, Olsson T, Turner BM, Cranston G, Allshire RC. Transient inhibition of histone deacetylation alters the structural and functional imprint at fission yeast centromeres. Cell. 1997 Dec 26;91(7):1021–1032. [PubMed]
  • Murphy TD, Karpen GH. Localization of centromere function in a Drosophila minichromosome. Cell. 1995 Aug 25;82(4):599–609. [PMC free article] [PubMed]
  • Grewal SI, Klar AJ. Chromosomal inheritance of epigenetic states in fission yeast during mitosis and meiosis. Cell. 1996 Jul 12;86(1):95–101. [PubMed]
  • Grewal SI, Bonaduce MJ, Klar AJ. Histone deacetylase homologs regulate epigenetic inheritance of transcriptional silencing and chromosome segregation in fission yeast. Genetics. 1998 Oct;150(2):563–576. [PMC free article] [PubMed]
  • Nimmo ER, Pidoux AL, Perry PE, Allshire RC. Defective meiosis in telomere-silencing mutants of Schizosaccharomyces pombe. Nature. 1998 Apr 23;392(6678):825–828. [PubMed]
  • Grimes B, Cooke H. Engineering mammalian chromosomes. Hum Mol Genet. 1998;7(10):1635–1640. [PubMed]
  • Niwa O, Matsumoto T, Chikashige Y, Yanagida M. Characterization of Schizosaccharomyces pombe minichromosome deletion derivatives and a functional allocation of their centromere. EMBO J. 1989 Oct;8(10):3045–3052. [PMC free article] [PubMed]
  • Hagan I, Yanagida M. Novel potential mitotic motor protein encoded by the fission yeast cut7+ gene. Nature. 1990 Oct 11;347(6293):563–566. [PubMed]
  • Platero JS, Hartnett T, Eissenberg JC. Functional analysis of the chromo domain of HP1. EMBO J. 1995 Aug 15;14(16):3977–3986. [PMC free article] [PubMed]
  • Hagan I, Yanagida M. Kinesin-related cut7 protein associates with mitotic and meiotic spindles in fission yeast. Nature. 1992 Mar 5;356(6364):74–76. [PubMed]
  • Pluta AF, Mackay AM, Ainsztein AM, Goldberg IG, Earnshaw WC. The centromere: hub of chromosomal activities. Science. 1995 Dec 8;270(5242):1591–1594. [PubMed]
  • Takahashi K, Yamada H, Yanagida M. Fission yeast minichromosome loss mutants mis cause lethal aneuploidy and replication abnormality. Mol Biol Cell. 1994 Oct;5(10):1145–1158. [PMC free article] [PubMed]
  • Reuter G, Wolff I. Isolation of dominant suppressor mutations for position-effect variegation in Drosophila melanogaster. Mol Gen Genet. 1981;182(3):516–519. [PubMed]
  • Thon G, Friis T. Epigenetic inheritance of transcriptional silencing and switching competence in fission yeast. Genetics. 1997 Mar;145(3):685–696. [PMC free article] [PubMed]
  • Saitoh S, Takahashi K, Yanagida M. Mis6, a fission yeast inner centromere protein, acts during G1/S and forms specialized chromatin required for equal segregation. Cell. 1997 Jul 11;90(1):131–143. [PubMed]
  • Thon G, Klar AJ. The clr1 locus regulates the expression of the cryptic mating-type loci of fission yeast. Genetics. 1992 Jun;131(2):287–296. [PMC free article] [PubMed]
  • Spencer F, Gerring SL, Connelly C, Hieter P. Mitotic chromosome transmission fidelity mutants in Saccharomyces cerevisiae. Genetics. 1990 Feb;124(2):237–249. [PMC free article] [PubMed]
  • Steiner NC, Clarke L. A novel epigenetic effect can alter centromere function in fission yeast. Cell. 1994 Dec 2;79(5):865–874. [PubMed]
  • Woods A, Sherwin T, Sasse R, MacRae TH, Baines AJ, Gull K. Definition of individual components within the cytoskeleton of Trypanosoma brucei by a library of monoclonal antibodies. J Cell Sci. 1989 Jul;93(Pt 3):491–500. [PubMed]
  • Steiner NC, Hahnenberger KM, Clarke L. Centromeres of the fission yeast Schizosaccharomyces pombe are highly variable genetic loci. Mol Cell Biol. 1993 Aug;13(8):4578–4587. [PMC free article] [PubMed]
  • Wines DR, Henikoff S. Somatic instability of a Drosophila chromosome. Genetics. 1992 Jul;131(3):683–691. [PMC free article] [PubMed]
  • Takahashi K, Murakami S, Chikashige Y, Funabiki H, Niwa O, Yanagida M. A low copy number central sequence with strict symmetry and unusual chromatin structure in fission yeast centromere. Mol Biol Cell. 1992 Jul;3(7):819–835. [PMC free article] [PubMed]

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