Mitotic Phosphorylation of Histone H3 Is Governed by Ipl1/aurora Kinase and Glc7/PP1 Phosphatase in Budding Yeast and Nematodes

Phosphorylation of histone H3 at serine 10 occurs during mitosis and meiosis in a wide range of eukaryotes and has been shown to be required for proper chromosome transmission in Tetrahymena. Here we report that Ipl1/aurora kinase and its genetically interacting phosphatase, Glc7/PP1, are responsible for the balance of H3 phosphorylation during mitosis in Saccharomyces cerevisiae and Caenorhabditis elegans. In these models, both enzymes are required for H3 phosphorylation and chromosome segregation, although a causal link between the two processes has not been demonstrated. Deregulation of human aurora kinases has been implicated in oncogenesis as a consequence of chromosome missegregation. Our findings reveal an enzyme system that regulates chromosome dynamics and controls histone phosphorylation that is conserved among diverse eukaryotes.

[1]  G. Roeder,et al.  ZIP1 is a synaptonemal complex protein required for meiotic chromosome synapsis , 1993, Cell.

[2]  S. Taylor The in vitro phosphorylation of chromatin by the catalytic subunit of cAMP-dependent protein kinase. , 1982, The Journal of biological chemistry.

[3]  C. Allis,et al.  Histone H3 phosphorylation is required for the initiation, but not maintenance, of mammalian chromosome condensation. , 1998, Journal of cell science.

[4]  J. Schumacher,et al.  A highly conserved centrosomal kinase, AIR-1, is required for accurate cell cycle progression and segregation of developmental factors in Caenorhabditis elegans embryos. , 1998, Development.

[5]  Xuetong Shen,et al.  Linker histories are not essential and affect chromatin condensation in vivo , 1995, Cell.

[6]  R. E. Esposito,et al.  The role of the SPO11 gene in meiotic recombination in yeast. , 1985, Genetics.

[7]  Clarence S. M. Chan,et al.  Type 1 protein phosphatase acts in opposition to IpL1 protein kinase in regulating yeast chromosome segregation , 1994, Molecular and cellular biology.

[8]  D. Glover,et al.  Mutations in aurora prevent centrosome separation leading to the formation of monopolar spindles , 1995, Cell.

[9]  A. Bloecher,et al.  Alanine-scanning mutagenesis of protein phosphatase type 1 in the yeast Saccharomyces cerevisiae. , 1997, Genetics.

[10]  J. Bischoff,et al.  The Aurora/Ipl1p kinase family: regulators of chromosome segregation and cytokinesis. , 1999, Trends in cell biology.

[11]  S. Carr,et al.  Mass Spectrometry in Biology & Medicine , 2000, Humana Press.

[12]  Jian Kuang,et al.  Tumour amplified kinase STK15/BTAK induces centrosome amplification, aneuploidy and transformation , 1998, Nature Genetics.

[13]  M. Inagaki,et al.  Identification of a Novel Phosphorylation Site on Histone H3 Coupled with Mitotic Chromosome Condensation* , 1999, The Journal of Biological Chemistry.

[14]  Andrew W. Murray,et al.  The Cell Cycle , 1989 .

[15]  K. Tatchell,et al.  The mutant type 1 protein phosphatase encoded by glc7-1 from Saccharomyces cerevisiae fails to interact productively with the GAC1-encoded regulatory subunit , 1994, Molecular and cellular biology.

[16]  M. Smith Mutations that affect chromosomal proteins in yeast. , 1991, Methods in cell biology.

[17]  P. Nurse A Long Twentieth Century of the Cell Cycle and Beyond , 2000, Cell.

[18]  Brian Schryver,et al.  A homologue of Drosophila aurora kinase is oncogenic and amplified in human colorectal cancers , 1998, The EMBO journal.

[19]  E. Bradbury,et al.  Phosphorylation of very-lysine-rich histone in Physarum polycephalum. Correlation with chromosome condensation. , 1973, European journal of biochemistry.

[20]  M. Smith,et al.  Chapter 19 Mutations That Affect Chromosomal Proteins in Yeast , 1991 .

[21]  J. Lieb,et al.  MIX-1: An Essential Component of the C. elegans Mitotic Machinery Executes X Chromosome Dosage Compensation , 1998, Cell.

[22]  C. Mello,et al.  RNAi in C. elegans: Soaking in the Genome Sequence , 1998, Science.

[23]  M. Inagaki,et al.  Mitosis-specific histone H3 phosphorylation in vitro in nucleosome structures. , 1990, European journal of biochemistry.

[24]  D. Botstein,et al.  Isolation and characterization of chromosome-gain and increase-in-ploidy mutants in yeast. , 1993, Genetics.

[25]  M. Dorée,et al.  The Xenopus protein kinase pEg2 associates with the centrosome in a cell cycle-dependent manner, binds to the spindle microtubules and is involved in bipolar mitotic spindle assembly. , 1998, Journal of cell science.

[26]  C. Prigent,et al.  Aurora/Ipl1p-related kinases, a new oncogenic family of mitotic serine-threonine kinases. , 1999, Journal of cell science.

[27]  S. Shenolikar,et al.  Protein serine/threonine phosphatases--new avenues for cell regulation. , 1994, Annual review of cell biology.

[28]  C. Allis,et al.  Requirement of Rsk-2 for epidermal growth factor-activated phosphorylation of histone H3. , 1999, Science.

[29]  J. Shabanowitz,et al.  Sequencing the Primordial Soup , 2000 .

[30]  T. Hirano Chromosome cohesion, condensation, and separation. , 2000, Annual review of biochemistry.

[31]  S. Kotani,et al.  Cell Cycle-dependent Expression and Spindle Pole Localization of a Novel Human Protein Kinase, Aik, Related to Aurora of Drosophila and Yeast Ipl1* , 1997, The Journal of Biological Chemistry.

[32]  D. Edmondson,et al.  Repression domain of the yeast global repressor Tup1 interacts directly with histones H3 and H4. , 1996, Genes & development.

[33]  D. Glover,et al.  One of the protein phosphatase 1 isoenzymes in Drosophila is essential for mitosis , 1990, Cell.

[34]  F. Sherman Getting started with yeast. , 1991, Methods in enzymology.

[35]  U. Wintersberger,et al.  Modification of histones during the mitotic and meiotic cycle of yeast , 1982, FEBS letters.

[36]  T. Schedl,et al.  GLD-1, a cytoplasmic protein essential for oocyte differentiation, shows stage- and sex-specific expression during Caenorhabditis elegans germline development. , 1996, Developmental biology.

[37]  M. Stark,et al.  Yeast Protein Serine/Threonine Phosphatases: Multiple Roles and Diverse Regulation , 1996, Yeast.

[38]  L. Mahadevan,et al.  MAP kinase-mediated signalling to nucleosomes and immediate-early gene induction. , 1999, Seminars in cell & developmental biology.

[39]  H. Katayama,et al.  Multinuclearity and increased ploidy caused by overexpression of the aurora- and Ipl1-like midbody-associated protein mitotic kinase in human cancer cells. , 1998, Cancer research.

[40]  W Hörz,et al.  Nuclease hypersensitive regions with adjacent positioned nucleosomes mark the gene boundaries of the PHO5/PHO3 locus in yeast. , 1986, The EMBO journal.

[41]  M. Dresser,et al.  Meiotic chromosome behavior in spread preparations of yeast , 1988, The Journal of cell biology.

[42]  L. R. Gurley,et al.  CELL CYCLE-SPECIFIC CHANGES IN HISTONE PHOSPHORYLATION ASSOCIATED WITH CELL PROLIFERATION AND CHROMOSOME CONDENSATION , 1974, The Journal of cell biology.

[43]  P. Cohen,et al.  An improved procedure for identifying and quantitating protein phosphatases in mammalian tissues , 1989, FEBS letters.

[44]  J. Schumacher,et al.  AIR-2: An Aurora/Ipl1-related Protein Kinase Associated with Chromosomes and Midbody Microtubules Is Required for Polar Body Extrusion and Cytokinesis in Caenorhabditis elegans Embryos , 1998, The Journal of cell biology.

[45]  A. Fire,et al.  Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans , 1998, Nature.

[46]  A. Hyman,et al.  Regulation of Saccharomyces cerevisiae kinetochores by the type 1 phosphatase Glc7p. , 1999, Genes & development.

[47]  J. Kimble,et al.  Genetic regulation of entry into meiosis in Caenorhabditis elegans. , 1998, Development.

[48]  R. A. Swank,et al.  Chromosome condensation induced by fostriecin does not require p34cdc2 kinase activity and histone H1 hyperphosphorylation, but is associated with enhanced histone H2A and H3 phosphorylation. , 1995, The EMBO journal.

[49]  S. Gout,et al.  Core histone N‐termini play an essential role in mitotic chromosome condensation , 2000, The EMBO journal.

[50]  K. Kemphues,et al.  par-1, a gene required for establishing polarity in C. elegans embryos, encodes a putative Ser/Thr kinase that is asymmetrically distributed , 1995, Cell.

[51]  T. Schedl,et al.  gld-1, a tumor suppressor gene required for oocyte development in Caenorhabditis elegans. , 1995, Genetics.

[52]  E. Villa-Moruzzi,et al.  Differential Subcellular Localization of Protein Phosphatase-1 α, γ1, and δ Isoforms during Both Interphase and Mitosis in Mammalian Cells , 1998, The Journal of cell biology.

[53]  M. Boxem,et al.  The Caenorhabditis elegans gene ncc-1 encodes a cdc2-related kinase required for M phase in meiotic and mitotic cell divisions, but not for S phase. , 1999, Development.

[54]  C. Allis,et al.  Mitosis-specific phosphorylation of histone H3 initiates primarily within pericentromeric heterochromatin during G2 and spreads in an ordered fashion coincident with mitotic chromosome condensation , 1997, Chromosoma.

[55]  K. Arndt,et al.  The SIT4 protein phosphatase is required in late G1 for progression into S phase. , 1991, Cold Spring Harbor symposia on quantitative biology.

[56]  K. Struhl Histone acetylation and transcriptional regulatory mechanisms. , 1998, Genes & development.

[57]  J. Hodgkin,et al.  Stu-71air-2 is a C. elegans aurora homologue essential for chromosome segregation during embryonic and post-embryonic development , 1999, Mechanisms of Development.

[58]  R. Lin,et al.  POP-1 and Anterior–Posterior Fate Decisions in C. elegans Embryos , 1998, Cell.

[59]  N. Munakata [Genetics of Caenorhabditis elegans]. , 1989, Tanpakushitsu kakusan koso. Protein, nucleic acid, enzyme.

[60]  Clarence S. M. Chan,et al.  Sli15 Associates with the Ipl1 Protein Kinase to Promote Proper Chromosome Segregation in Saccharomyces cerevisiae , 1999, The Journal of cell biology.

[61]  S. Chu,et al.  Gametogenesis in yeast is regulated by a transcriptional cascade dependent on Ndt80. , 1998, Molecular cell.

[62]  C. Allis,et al.  Phosphorylation of histone H3 at serine 10 is correlated with chromosome condensation during mitosis and meiosis in Tetrahymena. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[63]  A. Bloecher,et al.  Genetic interactions between GLC7, PPZ1 and PPZ2 in saccharomyces cerevisiae. , 2000, Genetics.

[64]  T. Toda,et al.  The fission yeast dis2 + gene required for chromosome disjoining encodes one of two putative type 1 protein phosphatases , 1989, Cell.

[65]  J. Doonan,et al.  The bimG gene of Aspergillus nidulans, required for completion of anaphase, encodes a homolog of mammalian phosphoprotein phosphatase 1 , 1989, Cell.

[66]  M. Tatsuka,et al.  AIM‐1: a mammalian midbody‐associated protein required for cytokinesis , 1998, The EMBO journal.

[67]  T. Kishimoto,et al.  Chromosome condensation in Xenopus mitotic extracts without histone H1. , 1993, Science.

[68]  C. Allis,et al.  Phosphorylation of linker histone is associated with transcriptional activation in a normally silent nucleus , 1996, The Journal of cell biology.

[69]  D. Botstein,et al.  The transcriptional program of sporulation in budding yeast. , 1998, Science.

[70]  Clarence S. M. Chan,et al.  A Novel Mammalian, Mitotic Spindle–associated Kinase Is Related to Yeast and Fly Chromosome Segregation Regulators , 1997, The Journal of cell biology.

[71]  C. Allis,et al.  Phosphorylation of Histone H3 Is Required for Proper Chromosome Condensation and Segregation , 1999, Cell.

[72]  A. Bloecher,et al.  Defects in Saccharomyces cerevisiae protein phosphatase type I activate the spindle/kinetochore checkpoint. , 1999, Genes & development.

[73]  A. Murray,et al.  The conserved protein kinase Ipl1 regulates microtubule binding to kinetochores in budding yeast. , 1999, Genes & development.

[74]  D. K. Bishop RecA homologs Dmc1 and Rad51 interact to form multiple nuclear complexes prior to meiotic chromosome synapsis , 1994, Cell.