Fission Yeast Mutants That Alleviate Transcriptional Silencing in Centromeric Flanking Repeats and Disrupt Chromosome Segregation

Corresponding author: Robin C. Allshire, MRC Human Genetics Unit, Western General Hospital, Crewe Rd., Edinburgh EH4 2XU, Scotland., robin.allshire{at}hgu.mrc.ac.uk (E-mail)

Communicating editor: G. R. SMITH

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°. 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.

This article has been cited by other articles:

				D. V. Irvine, D. B. Goto, M. W. Vaughn, Y. Nakaseko, W. R. McCombie, M. Yanagida, and R. Martienssen Mapping epigenetic mutations in fission yeast using whole-genome next-generation sequencing Genome Res., June 1, 2009; 19(6): 1077 - 1083. [Abstract] [Full Text] [PDF]

				E. H. Bayne, M. Portoso, A. Kagansky, I. C. Kos-Braun, T. Urano, K. Ekwall, F. Alves, J. Rappsilber, and R. C. Allshire Splicing Factors Facilitate RNAi-Directed Silencing in Fission Yeast Science, October 24, 2008; 322(5901): 602 - 606. [Abstract] [Full Text] [PDF]

				A. Greenall, E. S. Williams, K. A. Martin, J. M. Palmer, J. Gray, C. Liu, and S. K. Whitehall Hip3 Interacts with the HIRA Proteins Hip1 and Slm9 and Is Required for Transcriptional Silencing and Accurate Chromosome Segregation J. Biol. Chem., March 31, 2006; 281(13): 8732 - 8739. [Abstract] [Full Text] [PDF]

				J. Huang and D. Moazed Sister chromatid cohesion in silent chromatin: each sister to her own ring Genes & Dev., January 15, 2006; 20(2): 132 - 137. [Full Text] [PDF]

				I. Djupedal, M. Portoso, H. Spahr, C. Bonilla, C. M. Gustafsson, R. C. Allshire, and K. Ekwall RNA Pol II subunit Rpb7 promotes centromeric transcription and RNAi-directed chromatin silencing Genes & Dev., October 1, 2005; 19(19): 2301 - 2306. [Abstract] [Full Text] [PDF]

				E. Bernstein and C. D. Allis RNA meets chromatin Genes & Dev., July 15, 2005; 19(14): 1635 - 1655. [Abstract] [Full Text] [PDF]

				J. Walfridsson, P. Bjerling, M. Thalen, E.-J. Yoo, S. D. Park, and K. Ekwall The CHD remodeling factor Hrp1 stimulates CENP-A loading to centromeres Nucleic Acids Res., May 20, 2005; 33(9): 2868 - 2879. [Abstract] [Full Text] [PDF]

				A. L Pidoux and R. C Allshire The role of heterochromatin in centromere function Phil Trans R Soc B, March 29, 2005; 360(1455): 569 - 579. [Abstract] [Full Text] [PDF]

				K. R. Hansen, G. Burns, J. Mata, T. A. Volpe, R. A. Martienssen, J. Bahler, and G. Thon Global Effects on Gene Expression in Fission Yeast by Silencing and RNA Interference Machineries Mol. Cell. Biol., January 15, 2005; 25(2): 590 - 601. [Abstract] [Full Text] [PDF]

				E. A. Shestakova, Z. Mansuroglu, H. Mokrani, N. Ghinea, and E. Bonnefoy Transcription factor YY1 associates with pericentromeric {gamma}-satellite DNA in cycling but not in quiescent (G0) cells Nucleic Acids Res., August 17, 2004; 32(14): 4390 - 4399. [Abstract] [Full Text] [PDF]

				C. Blackwell, K. A. Martin, A. Greenall, A. Pidoux, R. C. Allshire, and S. K. Whitehall The Schizosaccharomyces pombe HIRA-Like Protein Hip1 Is Required for the Periodic Expression of Histone Genes and Contributes to the Function of Complex Centromeres Mol. Cell. Biol., May 15, 2004; 24(10): 4309 - 4320. [Abstract] [Full Text] [PDF]

				V. Schramke and R. Allshire Hairpin RNAs and Retrotransposon LTRs Effect RNAi and Chromatin-Based Gene Silencing Science, August 22, 2003; 301(5636): 1069 - 1074. [Abstract] [Full Text] [PDF]

				A. L. Pidoux, W. Richardson, and R. C. Allshire Sim4: a novel fission yeast kinetochore protein required for centromeric silencing and chromosome segregation J. Cell Biol., April 28, 2003; 161(2): 295 - 307. [Abstract] [Full Text] [PDF]

				R. K. Dawe RNA Interference, Transposons, and the Centromere PLANT CELL, February 1, 2003; 15(2): 297 - 301. [Full Text] [PDF]

				P. Provost, R. A. Silverstein, D. Dishart, J. Walfridsson, I. Djupedal, B. Kniola, A. Wright, B. Samuelsson, O. Radmark, and K. Ekwall Dicer is required for chromosome segregation and gene silencing in fission yeast cells PNAS, December 24, 2002; 99(26): 16648 - 16653. [Abstract] [Full Text] [PDF]

				T. A. Volpe, C. Kidner, I. M. Hall, G. Teng, S. I. S. Grewal, and R. A. Martienssen Regulation of Heterochromatic Silencing and Histone H3 Lysine-9 Methylation by RNAi Science, September 13, 2002; 297(5588): 1833 - 1837. [Abstract] [Full Text] [PDF]

				I. Sig Nielsen, O. Nielsen, J. M. Murray, and G. Thon The Fission Yeast Ubiquitin-Conjugating Enzymes UbcP3, Ubc15, and Rhp6 Affect Transcriptional Silencing of the Mating-Type Region Eukaryot. Cell, August 1, 2002; 1(4): 613 - 625. [Abstract] [Full Text] [PDF]

				H. Nakagawa, J.-K. Lee, J. Hurwitz, R. C. Allshire, J.-i. Nakayama, S. I.S. Grewal, K. Tanaka, and Y. Murakami Fission yeast CENP-B homologs nucleate centromeric heterochromatin by promoting heterochromatin-specific histone tail modifications Genes & Dev., July 15, 2002; 16(14): 1766 - 1778. [Abstract] [Full Text] [PDF]

				D. Sandhu, D. Sidhu, and K. S. Gill Identification of Expressed Sequence Markers for a Major Gene-Rich Region of Wheat Chromosome Group 1 Using RNA Fingerprinting-Differential Display Crop Sci., July 1, 2002; 42(4): 1285 - 1290. [Abstract] [Full Text] [PDF]

				Y. Huang Transcriptional silencing in Saccharomyces cerevisiae and Schizosaccharomyces pombe Nucleic Acids Res., April 1, 2002; 30(7): 1465 - 1482. [Abstract] [Full Text] [PDF]

				K. M. Donaldson, A. Lui, and G. H. Karpen Modifiers of Terminal Deficiency-Associated Position Effect Variegation in Drosophila Genetics, March 1, 2002; 160(3): 995 - 1009. [Abstract] [Full Text] [PDF]

				S. Rajagopalan and M. K. Balasubramanian Schizosaccharomyces pombe Bir1p, a Nuclear Protein That Localizes to Kinetochores and the Spindle Midzone, Is Essential for Chromosome Condensation and Spindle Elongation During Mitosis Genetics, February 1, 2002; 160(2): 445 - 456. [Abstract] [Full Text] [PDF]

				J. A. Sharp, A. A. Franco, M. A. Osley, and P. D. Kaufman Chromatin assembly factor I and Hir proteins contribute to building functional kinetochores in S. cerevisiae Genes & Dev., January 1, 2002; 16(1): 85 - 100. [Abstract] [Full Text] [PDF]

				B. Kniola, E. O'Toole, J. R. McIntosh, B. Mellone, R. Allshire, S. Mengarelli, K. Hultenby, and K. Ekwall The Domain Structure of Centromeres Is Conserved from Fission Yeast to Humans Mol. Biol. Cell, September 1, 2001; 12(9): 2767 - 2775. [Abstract] [Full Text] [PDF]

				S. Henikoff, K. Ahmad, and H. S. Malik The Centromere Paradox: Stable Inheritance with Rapidly Evolving DNA Science, August 10, 2001; 293(5532): 1098 - 1102. [Abstract] [Full Text] [PDF]

				K. A. Maggert and G. H. Karpen The Activation of a Neocentromere in Drosophila Requires Proximity to an Endogenous Centromere Genetics, August 1, 2001; 158(4): 1615 - 1628. [Abstract] [Full Text] [PDF]

				A. Pidoux, S Uzawa, P. Perry, W. Cande, and R. Allshire Live analysis of lagging chromosomes during anaphase and their effect on spindle elongation rate in fission yeast J. Cell Sci., January 12, 2000; 113(23): 4177 - 4191. [Abstract] [PDF]