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Molecular basis of centromeric chromatin required for equal chromosome segregation

Research Project

Project/Area Number 14380334
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Cell biology
Research InstitutionKurume University

Principal Investigator

TAKAHASHI Kohta  Kurume University, Institute of Life Science, Professor, 分子生命科学研究所, 教授 (40303804)

Project Period (FY) 2002 – 2004
Project Status Completed (Fiscal Year 2004)
Budget Amount *help
¥14,700,000 (Direct Cost: ¥14,700,000)
Fiscal Year 2004: ¥5,000,000 (Direct Cost: ¥5,000,000)
Fiscal Year 2003: ¥5,000,000 (Direct Cost: ¥5,000,000)
Fiscal Year 2002: ¥4,700,000 (Direct Cost: ¥4,700,000)
KeywordsChromosome / Centromere / CENP-A / Fission yeast / Nucleosome
Research Abstract

CENP-A is a centromere-specific histone H3 variant, essential for faithful chromosome segregation. We genetically identified two factors, Mis6 and Ams2, each of which is required for the correct centromere localisation of Cnp1, the fission yeast homologue of CENP-A. In this project, we elucidated following molecular features of Mis6, Ams2 and Cnp1.
1.As a multicopy suppressor for mis6-302 mutant, we identified Sim4/Mix1 which forms a stable complex with Mis6. We showed that the Mis6-Sim4 subcomplex is required for mitotic localization of Mad2, but not Bub1, spindle checkpoint protein at centromeres. Furthermore, we demonstrated that Nuf2 is required for maintaining the Mis6-complex on the kinetochore during mitosis. The Mis6-complex physically interacts with Mad2 under the condition that the Mad2-dependent checkpoint is activated. Ectopically expressed Mis6^<1-265> fragment localizes along the mitotic spindle, highlighting the potential binding ability of Mis6 to the spindle microtubule … More s. We propose that the Mis6-complex, in collaboration with the Nuf2-complex, monitors the spindle-kinetochore attachment state and act as a platform for Mad2 to accumulate at unattached kinetochores.
2.We demonstrated that there are at least two distinct phases of Cnp1 loading during the cell cycle. A GATA-type transcription factor, Ams2, promotes transcriptional activation of histone genes during S phase and aids in efficient loading of Cnp1 into duplicated centromeres. In Ams2-null cells, Cnp1 fails to localise to centromeres following the passage of S phase ; however, it accumulates again gradually via a backup reloading pathway, which occurs during G2, the gap phase between DNA replication and nuclear division in mitosis. Shortening of G2 length in Ams2-null cells results in marked reduction of Cnp1 accumulation at centromeres, leading to mitotic cell death with chromosome missegregation. The flexibility of Cnp1 loading may account for the plasticity of centromere formation when the authentic centromere is damaged. Less

Report

(4 results)
  • 2004 Annual Research Report   Final Research Report Summary
  • 2003 Annual Research Report
  • 2002 Annual Research Report
  • Research Products

    (26 results)

All 2005 2004 2003 2002 Other

All Journal Article (20 results) Book (3 results) Publications (3 results)

  • [Journal Article] Spindle checkpoint signaling requires the Mis6 kinetochore subcomplex, which interacts with Mad2 and mitotic spindles.2005

    • Author(s)
      Saitoh S
    • Journal Title

      Molecular Biology of the Cell in press

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Two distinct pathways responsible for the loading of CENP-A to centromeres in the fission yeast cell cycle.2005

    • Author(s)
      Takahashi K
    • Journal Title

      Philosophical Transactions of the Royal Society B 360

      Pages: 595-607

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] BAF53/Arp4 homolog Alp5 in fission yeast is required for histone H4 acetylation, kinetochore-spindle attachment, and gene silencing at centromere.2005

    • Author(s)
      Minoda A
    • Journal Title

      Molecular Biology of the Cell 16

      Pages: 316-327

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Two distinct pathways responsible for the loading of CENP-A to centromeres in the fission yeast cell cycle.2005

    • Author(s)
      Takahashi K, Takayama Y, Masuda F, Kobayashi Y, Saitoh S
    • Journal Title

      Philosophical Transactions of the Royal Society B 360

      Pages: 595-607

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] BAF53/Arp4 homolog Alp5 in fission yeast is required for histone H4 acetylation, kinetochore-spindle attachment, and gene silencing at centromere.2005

    • Author(s)
      Minoda A, Saitoh S, Takahashi K, Toda T.
    • Journal Title

      Molecular Biology of the Cell 16

      Pages: 316-327

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Two distinct pathways responsible for the loading of CENP-A to centromeres in the fission yeast cell cycle.2005

    • Author(s)
      Kohta Takahashi
    • Journal Title

      Philos.Trans.R.Soc.Lond.B.Biol.Sci. in press

    • Related Report
      2004 Annual Research Report
  • [Journal Article] BAF53/Arp4 homolog Alp5 in fission yeast is required for histone H4 acetylation, kinetochore-spindle attachment, and gene silencing at centromere.2005

    • Author(s)
      Aki Minoda
    • Journal Title

      Mol Biol Cell 16・1

      Pages: 316-327

    • Related Report
      2004 Annual Research Report
  • [Journal Article] An interactive gene network for securin-separase, condensin, cohesin, Dis1/Mtc1 and histones constructed by mass transformation.2004

    • Author(s)
      Yuasa T
    • Journal Title

      Genes to Cells 9

      Pages: 1069-1082

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Mis16 and Mis18 are required for CENP-A loading and histone deacetylation at centromeres.2004

    • Author(s)
      Hayashi T
    • Journal Title

      Cell 118

      Pages: 715-729

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] An interactive gene network for securin-separase, condensin, cohesin, Dis1/Mtc1 and histones constructed by mass transformation.2004

    • Author(s)
      Yuasa T, Hayashi T, Ikai N, Katayama T, Aoki K, Obara T, Toyoda Y, Maruyama T, Kitagawa D, Takahashi K, Nagao K, Nakaseko Y, Yanagida M.
    • Journal Title

      Genes to Cells 9

      Pages: 1069-1082

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Mis16 and Mis18 are required for CENP-A loading and histone deacetylation at centromeres.2004

    • Author(s)
      Hayashi T, Fujita Y, Iwasaki O, Adachi Y, Takahashi K, Yanagida M.
    • Journal Title

      Cell 118

      Pages: 715-729

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] An interactive gene network for securin-separase, condensin, cohesin, Dis1/Mtc1 and histones constructed by mass transformation.2004

    • Author(s)
      Tatsuro Yuasa
    • Journal Title

      Genes Cells 9・11

      Pages: 1069-1082

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Mis16 and Mis18 are required for CENP-A loading and histone deacetylation at centromeres.2004

    • Author(s)
      Takeshi Hayashi
    • Journal Title

      Cell 118・6

      Pages: 715-729

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Does a GATA factor make a bed for centromeric nucleosomes?2003

    • Author(s)
      Chen ES
    • Journal Title

      Cell Cycle 12

      Pages: 277-278

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] A cell cycle-regulated GATA factor promotes centromeric localization of CENP-A in fission yeast.2003

    • Author(s)
      Chen ES
    • Journal Title

      Molecular Cell 11

      Pages: 175-187

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Does a GATA factor make a bed for centromeric nucleosomes?2003

    • Author(s)
      Chen ES, Yanagida M, Takahashi K.
    • Journal Title

      Cell Cycle 12

      Pages: 277-278

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] A cell cycle-regulated GATA factor promotes centromeric localization of CENP-A in fission yeast.2003

    • Author(s)
      Chen ES, Saitoh S, Yanagida M, Takahashi K.
    • Journal Title

      Molecular Cell 11

      Pages: 175-187

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Requirement of chromatid cohesion proteins rad21/scc1 and mis4/scc2 for normal spindle-kinetochore interaction in fission yeast.2002

    • Author(s)
      Toyoda Y
    • Journal Title

      Curr Biology 12

      Pages: 347-358

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Requirement of chromatid cohesion proteins rad21/scc1 and mis4/scc2 for normal spindle-kinetochore interaction in fission yeast.2002

    • Author(s)
      Toyoda Y, Furuya K, Goshima G, Nagao K, Takahashi K, Yanagida M.
    • Journal Title

      Curr Biology 12

      Pages: 347-358

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Spindle checkpoint signaling requires the Mis6 kinetochore subcomplex, which interacts with Mad2 and mitotic spindles.

    • Author(s)
      Saitoh S, Ishii K, Kobayashi Y, Takahashi K
    • Journal Title

      Molecular Biology of the Cell (in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Book] Chromosome cohesion and segregation. In The Molecular Biology in Fission Yeast (Egel R., Ed.)2004

    • Author(s)
      Takahashi K
    • Total Pages
      450
    • Publisher
      Springer-Verlag Inc.
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Book] Chromosome cohesion and segregation. The Molecular Biology in Fission Yeast (Egel R., Ed.)2004

    • Author(s)
      Takahashi K, Yanagida M.
    • Publisher
      Springer-Verlag Inc.
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Book] Chromosome cohesion and segregation. in "The molecular biology in fission yeast"2003

    • Author(s)
      Kohta Takahashi
    • Total Pages
      450
    • Publisher
      Egel R.,Ed.,Springer-Verlag
    • Related Report
      2004 Annual Research Report
  • [Publications] Ee Sin Chen: "Does a GATA factor make the bed for centromeric nucleosomes?"Cell Cycle. 2巻・4号. 277-278 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Ee Sin Chen: "A cell cycle-regulated GATA factor promotes centromeric localization of CENP-A in fission yeast"Molecular Cell. 11(1). 175-187 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Yusuke Toyoda: "Requirement of chromatid cohesion proteins rad21/sccl and mis4/scc2 for normal spindle-kinetochore interaction in fission yeast"Current Biology. 12(5). 347-358 (2002)

    • Related Report
      2002 Annual Research Report

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Published: 2002-04-01   Modified: 2016-04-21  

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