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Genetics. Nov 2000; 156(3): 973–981.
PMCID: PMC1461345

CSE4 genetically interacts with the Saccharomyces cerevisiae centromere DNA elements CDE I and CDE II but not CDE III. Implications for the path of the centromere dna around a cse4p variant nucleosome.

Abstract

Each Saccharomyces cerevisiae chromosome contains a single centromere composed of three conserved DNA elements, CDE I, II, and III. The histone H3 variant, Cse4p, is an essential component of the S. cerevisiae centromere and is thought to replace H3 in specialized nucleosomes at the yeast centromere. To investigate the genetic interactions between Cse4p and centromere DNA, we measured the chromosome loss rates exhibited by cse4 cen3 double-mutant cells that express mutant Cse4 proteins and carry chromosomes containing mutant centromere DNA (cen3). When compared to loss rates for cells carrying the same cen3 DNA mutants but expressing wild-type Cse4p, we found that mutations throughout the Cse4p histone-fold domain caused surprisingly large increases in the loss of chromosomes carrying CDE I or CDE II mutant centromeres, but had no effect on chromosomes with CDE III mutant centromeres. Our genetic evidence is consistent with direct interactions between Cse4p and the CDE I-CDE II region of the centromere DNA. On the basis of these and other results from genetic, biochemical, and structural studies, we propose a model that best describes the path of the centromere DNA around a specialized Cse4p-nucleosome.

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Selected References

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  • Baker RE, Masison DC. Isolation of the gene encoding the Saccharomyces cerevisiae centromere-binding protein CP1. Mol Cell Biol. 1990 Jun;10(6):2458–2467. [PMC free article] [PubMed]
  • Baker RE, Fitzgerald-Hayes M, O'Brien TC. Purification of the yeast centromere binding protein CP1 and a mutational analysis of its binding site. J Biol Chem. 1989 Jun 25;264(18):10843–10850. [PubMed]
  • Luger K, Mäder AW, Richmond RK, Sargent DF, Richmond TJ. Crystal structure of the nucleosome core particle at 2.8 A resolution. Nature. 1997 Sep 18;389(6648):251–260. [PubMed]
  • Baker RE, Harris K, Zhang K. Mutations synthetically lethal with cep1 target S. cerevisiae kinetochore components. Genetics. 1998 May;149(1):73–85. [PMC free article] [PubMed]
  • McGrew J, Diehl B, Fitzgerald-Hayes M. Single base-pair mutations in centromere element III cause aberrant chromosome segregation in Saccharomyces cerevisiae. Mol Cell Biol. 1986 Feb;6(2):530–538. [PMC free article] [PubMed]
  • Baxevanis AD, Arents G, Moudrianakis EN, Landsman D. A variety of DNA-binding and multimeric proteins contain the histone fold motif. Nucleic Acids Res. 1995 Jul 25;23(14):2685–2691. [PMC free article] [PubMed]
  • McGrew JT, Xiao ZX, Fitzgerald-Hayes M. Saccharomyces cerevisiae mutants defective in chromosome segregation. Yeast. 1989 Jul-Aug;5(4):271–284. [PubMed]
  • Bloom KS, Carbon J. Yeast centromere DNA is in a unique and highly ordered structure in chromosomes and small circular minichromosomes. Cell. 1982 Jun;29(2):305–317. [PubMed]
  • Meluh PB, Koshland D. Evidence that the MIF2 gene of Saccharomyces cerevisiae encodes a centromere protein with homology to the mammalian centromere protein CENP-C. Mol Biol Cell. 1995 Jul;6(7):793–807. [PMC free article] [PubMed]
  • Bram RJ, Kornberg RD. Isolation of a Saccharomyces cerevisiae centromere DNA-binding protein, its human homolog, and its possible role as a transcription factor. Mol Cell Biol. 1987 Jan;7(1):403–409. [PMC free article] [PubMed]
  • Meluh PB, Yang P, Glowczewski L, Koshland D, Smith MM. Cse4p is a component of the core centromere of Saccharomyces cerevisiae. Cell. 1998 Sep 4;94(5):607–613. [PubMed]
  • Murphy MR, Fowlkes DM, Fitzgerald-Hayes M. Analysis of centromere function in Saccharomyces cerevisiae using synthetic centromere mutants. Chromosoma. 1991 Dec;101(3):189–197. [PubMed]
  • Chen Y, Baker RE, Keith KC, Harris K, Stoler S, Fitzgerald-Hayes M. The N terminus of the centromere H3-like protein Cse4p performs an essential function distinct from that of the histone fold domain. Mol Cell Biol. 2000 Sep;20(18):7037–7048. [PMC free article] [PubMed]
  • Ortiz J, Stemmann O, Rank S, Lechner J. A putative protein complex consisting of Ctf19, Mcm21, and Okp1 represents a missing link in the budding yeast kinetochore. Genes Dev. 1999 May 1;13(9):1140–1155. [PMC free article] [PubMed]
  • Cumberledge S, Carbon J. Mutational analysis of meiotic and mitotic centromere function in Saccharomyces cerevisiae. Genetics. 1987 Oct;117(2):203–212. [PMC free article] [PubMed]
  • Palmer DK, O'Day K, Wener MH, Andrews BS, Margolis RL. A 17-kD centromere protein (CENP-A) copurifies with nucleosome core particles and with histones. J Cell Biol. 1987 Apr;104(4):805–815. [PMC free article] [PubMed]
  • Fitzgerald-Hayes M, Clarke L, Carbon J. Nucleotide sequence comparisons and functional analysis of yeast centromere DNAs. Cell. 1982 May;29(1):235–244. [PubMed]
  • Funk M, Hegemann JH, Philippsen P. Chromatin digestion with restriction endonucleases reveals 150-160 bp of protected DNA in the centromere of chromosome XIV in Saccharomyces cerevisiae. Mol Gen Genet. 1989 Oct;219(1-2):153–160. [PubMed]
  • Schulman I, Bloom KS. Centromeres: an integrated protein/DNA complex required for chromosome movement. Annu Rev Cell Biol. 1991;7:311–336. [PubMed]
  • Gaudet A, Fitzgerald-Hayes M. Alterations in the adenine-plus-thymine-rich region of CEN3 affect centromere function in Saccharomyces cerevisiae. Mol Cell Biol. 1987 Jan;7(1):68–75. [PMC free article] [PubMed]
  • Shelby RD, Vafa O, Sullivan KF. Assembly of CENP-A into centromeric chromatin requires a cooperative array of nucleosomal DNA contact sites. J Cell Biol. 1997 Feb 10;136(3):501–513. [PMC free article] [PubMed]
  • Hegemann JH, Shero JH, Cottarel G, Philippsen P, Hieter P. Mutational analysis of centromere DNA from chromosome VI of Saccharomyces cerevisiae. Mol Cell Biol. 1988 Jun;8(6):2523–2535. [PMC free article] [PubMed]
  • Smith MM, Yang P, Santisteban MS, Boone PW, Goldstein AT, Megee PC. A novel histone H4 mutant defective in nuclear division and mitotic chromosome transmission. Mol Cell Biol. 1996 Mar;16(3):1017–1026. [PMC free article] [PubMed]
  • Henikoff S, Ahmad K, Platero JS, van Steensel B. Heterochromatic deposition of centromeric histone H3-like proteins. Proc Natl Acad Sci U S A. 2000 Jan 18;97(2):716–721. [PMC free article] [PubMed]
  • Stoler S, Keith KC, Curnick KE, Fitzgerald-Hayes M. A mutation in CSE4, an essential gene encoding a novel chromatin-associated protein in yeast, causes chromosome nondisjunction and cell cycle arrest at mitosis. Genes Dev. 1995 Mar 1;9(5):573–586. [PubMed]
  • Huffaker TC, Hoyt MA, Botstein D. Genetic analysis of the yeast cytoskeleton. Annu Rev Genet. 1987;21:259–284. [PubMed]
  • Keith KC, Baker RE, Chen Y, Harris K, Stoler S, Fitzgerald-Hayes M. Analysis of primary structural determinants that distinguish the centromere-specific function of histone variant Cse4p from histone H3. Mol Cell Biol. 1999 Sep;19(9):6130–6139. [PMC free article] [PubMed]
  • Strunnikov AV, Kingsbury J, Koshland D. CEP3 encodes a centromere protein of Saccharomyces cerevisiae. J Cell Biol. 1995 Mar;128(5):749–760. [PMC free article] [PubMed]
  • Sullivan KF, Hechenberger M, Masri K. Human CENP-A contains a histone H3 related histone fold domain that is required for targeting to the centromere. J Cell Biol. 1994 Nov;127(3):581–592. [PMC free article] [PubMed]
  • Kent NA, Tsang JS, Crowther DJ, Mellor J. Chromatin structure modulation in Saccharomyces cerevisiae by centromere and promoter factor 1. Mol Cell Biol. 1994 Aug;14(8):5229–5241. [PMC free article] [PubMed]
  • Vafa O, Sullivan KF. Chromatin containing CENP-A and alpha-satellite DNA is a major component of the inner kinetochore plate. Curr Biol. 1997 Nov 1;7(11):897–900. [PubMed]

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