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2011 Fiscal Year Final Research Report

Role of kinetochore stretching in controlling the spindle-assembly checkpoint

Research Project

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Project/Area Number 21370082
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Molecular biology
Research Institution公益財団法人がん研究会 (2011)
Japanese Foundation For Cancer Research (2009-2010)

Principal Investigator

HIROTA Toru  公益財団法人がん研究会, がん研究所実験病理部, 部長 (50421368)

Co-Investigator(Renkei-kenkyūsha) 高垣 謙太郎  公益財団法人がん研究会, がん研究所・実験病理部, 博士研究員 (70419951)
内田 和彦  公益財団法人がん研究会, がん研究所・実験病理部, 博士研究員 (40380555)
進藤 軌久  公益財団法人がん研究会, がん研究所・実験病理部, 博士研究員 (00512253)
熊田 和貴  公益財団法人がん研究会, がん研究所・実験病理部, 博士研究員 (10370149)
Project Period (FY) 2009 – 2011
Keywords細胞分裂 / 染色体 / 動原体 / 微小管 / M期チェックポイント / 中期後期移行
Research Abstract

Faithful segregation of chromosomes relies on the spindle-assembly checkpoint(SAC), which delays anaphase onset until all kinetochores are attached to microtubules(MT). The SAC monitors MT attachment at kinetochores, but whether it also senses the presence of 'tension' has long been a matter of debate. We found that 'tension' applied across sister kinetochores, which stretches centromeres, is dispensable, but stretching of kinetochores is required for silencing the SAC(Uchida et al., 2009). It is therefore crucial to investigate if 'tension' underlies kinetochore stretching. We addressed this question experimentally by engineering the conditions that microtubules are attached to kinetochors but free from the pulling force. Under these conditions, we found that kinetochores underwent stretching upon MT attachment. These results suggest that intact kinetochore-pulling force is not required for kinetochore stretching, thus challenging the notion that SAC directly monitors the presence of tension.

  • Research Products

    (52 results)

All 2012 2011 2010 2009 Other

All Journal Article (9 results) (of which Peer Reviewed: 9 results) Presentation (37 results) Book (5 results) Remarks (1 results)

  • [Journal Article] The initial phase of chromosome condensation requires Cdk1-mediated phosphorylation of the CAP-D3 subunit of condensin II2011

    • Author(s)
      Abe, S., Nagasaka, K., Hirayama, Y., Kozuka-Hata, H., Oyama, M., Aoyagi, Y., Obuse, C., and Hirota, T
    • Journal Title

      Genes Dev

      Volume: 25 Pages: 863-874

    • Peer Reviewed
  • [Journal Article] CAMP(C13orf8, ZNF828) is a novel regulator of kinetochore-microtubule attachment2011

    • Author(s)
      Ito, G., Kanno, S., Uchida, K. S. K, Chiba, S., Sugino, S., Watanabe, K., Mizuno, K., Yasui, A., Hirota, T., and Tanaka, K
    • Journal Title

      EMBO J

      Volume: 30 Pages: 130-134

    • Peer Reviewed
  • [Journal Article] Differential control of Eg5 dependent centrosome separation by Plk1 and Cdk12011

    • Author(s)
      Smith, E., Hegarat, N., Vesely, C., Roseboom, I., Streicher, H., Straatman, K., Flynn, H., Skehel, M., Hirota, T., Kuriyama, R., Hochegger, H
    • Journal Title

      EMBO J

      Volume: 30 Pages: 2233-2245

    • Peer Reviewed
  • [Journal Article] A single starfish Aurora performs dual functions of Auroras A and B in human cells2010

    • Author(s)
      Abe, Y., Okumura, E., Hosoya, T., Hirota, T., and Kishimoto, T.
    • Journal Title

      J. Cell Sci

      Volume: 123 Pages: 3978-3988

    • Peer Reviewed
  • [Journal Article] Human POGZ modulates HP1 dissociation from mitotic chromosome arms through Aurora B activation2010

    • Author(s)
      Nozawa, R., Nagao, K., Masuda, H., Iwasaki, O., Hirota, T., Nozaki, N., Kimura, H., and Obuse, C.
    • Journal Title

      Nat. Cell Biol

      Volume: 12 Pages: 719-727

    • Peer Reviewed
  • [Journal Article] TRF1 mediates mitotic abnormalities induced by Aurora-A overexpression2010

    • Author(s)
      Ohishi, T., Hirota, T., Tsuruo, T., Seimiya, H.
    • Journal Title

      Cancer Res

      Volume: 70 Pages: 2041-2052

    • Peer Reviewed
  • [Journal Article] Requirement of ATM for Rapid p53 Phosphorylation at Ser46 without Ser/Thr-Gln Sequences2010

    • Author(s)
      Kodama, M., Otsubo, C., Hirota, T., Yokota, J., Enari, M., Taya, Y
    • Journal Title

      Mol. Cell. Biol

      Volume: 30 Pages: 1620-1633

    • Peer Reviewed
  • [Journal Article] Kinetochore stretching inactivates the spindle assembly checkpoint2009

    • Author(s)
      Uchida, K. S. K., Takagaki, K., Kumada, K, Noda, T., and Hirota, T
    • Journal Title

      J. Cell Biol

      Volume: 184 Pages: 384-390

    • Peer Reviewed
  • [Journal Article] Chromosome segregation machinery and cancer2009

    • Author(s)
      Tanaka, K., and Hirota, T
    • Journal Title

      Cancer Sci

      Volume: 100 Pages: 1158-1165

    • Peer Reviewed
  • [Presentation] Separaseは染色体分離において一人二役を果たす2012

    • Author(s)
      進藤軌久、広田亨
    • Organizer
      第29回染色体ワークショップ
    • Place of Presentation
      秋保温泉
    • Year and Date
      20120125-27
  • [Presentation] Separaseの自己切断による染色体分配制御2012

    • Author(s)
      熊田和貴、広田亨
    • Organizer
      第29回染色体ワークショップ
    • Place of Presentation
      秋保温泉
    • Year and Date
      20120125-27
  • [Presentation] アナログ感受性変異体によるGreatwallキナーゼの機能解析2012

    • Author(s)
      阿部優介、広田亨
    • Organizer
      第29回染色体ワークショップ
    • Place of Presentation
      秋保温泉
    • Year and Date
      20120125-27
  • [Presentation] がん細胞における異数性の発生要因を考える2012

    • Author(s)
      広田亨
    • Organizer
      第28回新潟県立中央病院集談会・特別講演
    • Place of Presentation
      上越
    • Year and Date
      2012-03-02
  • [Presentation] Probing separase activity reveals its switch-like activation at the metaphase-to-anaphase transition2011

    • Author(s)
      Hirota, T
    • Organizer
      第30回日本分子生物学会.シンポジウム
    • Place of Presentation
      横浜
    • Year and Date
      20111213-16
  • [Presentation] Does the spindle-assembly checkpoint monitor the presence of tension2011

    • Author(s)
      Uchida, K. S. K., Hirota, T.
    • Organizer
      第30回日本分子生物学会・ワークショップ
    • Place of Presentation
      横浜
    • Year and Date
      20111213-16
  • [Presentation] Dual role of separase during the metaphase-to-anaphase transition ensures chromosome segregation in mammalian cells2011

    • Author(s)
      Shindo, N., Hirota, T.
    • Organizer
      Annual meeting of American Society of Cell Biology
    • Place of Presentation
      Denver
    • Year and Date
      20111203-09
  • [Presentation] Probing separase activity reveals its switch-like activation at the metaphase-to-anaphase transition2011

    • Author(s)
      Hirota, T
    • Organizer
      The MEXT Priority Research International Symposium Cell Division
    • Place of Presentation
      Hakone
    • Year and Date
      20110629-0701
  • [Presentation] Probing separase activity reveals its switch-like activation at the metaphase-to-anaphase transition2011

    • Author(s)
      Hirota, T
    • Organizer
      The 2^<nd> Dynamic Kinetochore Workshop
    • Place of Presentation
      Vienna
    • Year and Date
      20110615-18
  • [Presentation] がん細胞における異数性の発生要因を考える2011

    • Author(s)
      広田亨
    • Organizer
      第52回日本臨床細胞学会総会
    • Place of Presentation
      福岡
    • Year and Date
      20110520-22
  • [Presentation] How chromosome assembly is triggered in cells entering mitosis2011

    • Author(s)
      Hirota, T
    • Organizer
      6th UK-Japan Cell Cycle Meeting
    • Place of Presentation
      Windermere
    • Year and Date
      20110410-13
  • [Presentation] Cdk1によるCondensin IIのリン酸化が染色体凝縮を誘導する2011

    • Author(s)
      長坂浩太、阿部聡司、広田亨
    • Organizer
      第28回染色体ワークショップ
    • Place of Presentation
      山代温泉
    • Year and Date
      20110111-13
  • [Presentation] セパレースの可視化でわかってきたこと2011

    • Author(s)
      進藤軌久、広田亨
    • Organizer
      第28回染色体ワークショップ
    • Place of Presentation
      山代温泉
    • Year and Date
      20110111-13
  • [Presentation] 新規Mad2L2結合分子CAMPによるキネトコア-微小管結合の制御2011

    • Author(s)
      田中耕三、伊藤剛、安井明、広田亨
    • Organizer
      第28回染色体ワークショップ
    • Place of Presentation
      山代温泉
    • Year and Date
      20110111-13
  • [Presentation] How mitotic kinases control chromosome segregation2011

    • Author(s)
      Hirota, T.
    • Organizer
      熊本大学GCOE・リエゾンラボ研究会
    • Place of Presentation
      熊本
    • Year and Date
      2011-11-02
  • [Presentation] 染色体分離の正確性を保証するメカニズム2011

    • Author(s)
      広田亨
    • Organizer
      ケミカルバイオロジー勉強会・理化学研究所
    • Place of Presentation
      和光
    • Year and Date
      2011-10-26
  • [Presentation] Heterochromatin protein 1 is an essential component of the chromosomal passenger complex to prevent missegregation of chromosomes2011

    • Author(s)
      Hirota, T
    • Organizer
      平成23年度遺伝研研究会クロマチンダイナミクスの分子機構
    • Place of Presentation
      三島
    • Year and Date
      2011-10-20
  • [Presentation] The switch-like activation of separase ensures chromosome segregation2011

    • Author(s)
      Hirota, T
    • Organizer
      The GCOE International Workshop Mitosis
    • Place of Presentation
      Yokohama
    • Year and Date
      2011-07-04
  • [Presentation] 染色体分離の同期性を保証するメカニズム2011

    • Author(s)
      広田亨
    • Organizer
      北海道大学大学院・先端生命科学研究院・分子生物学特別セミナー
    • Place of Presentation
      札幌
    • Year and Date
      2011-06-24
  • [Presentation] How chromosome assembly is triggered in cells entering mitosis2011

    • Author(s)
      Hirota, T
    • Organizer
      Impromptu Seminar at the IMP
    • Place of Presentation
      Vienna
    • Year and Date
      2011-04-14
  • [Presentation] The initial phase of chromosome condensation requires Cdk1-mediated phosphorylation of the CAP-D3 subunit of condensin II2010

    • Author(s)
      長坂浩太、阿部聡司、広田亨
    • Organizer
      第33回日本分子生物学会年会
    • Place of Presentation
      横浜
    • Year and Date
      20101207-10
  • [Presentation] Charactrization of the Smc5/6 complex in human cells2010

    • Author(s)
      リナ・マルセロ・ガジェゴ・パエツ、坂東優篤、広田亨、白髭克彦
    • Organizer
      第33回日本分子生物学会年会
    • Place of Presentation
      横浜
    • Year and Date
      20101207-10
  • [Presentation] Aurora BはHP1αの動態制御を介し安定した染色体分配を保証する2010

    • Author(s)
      高垣謙太郎、内田和彦、広田亨
    • Organizer
      第69回日本癌学会学術総会
    • Place of Presentation
      大阪
    • Year and Date
      20100920-22
  • [Presentation] 新規Mad2L2結合分子CAMPによるキネトコア-微小管結合の制御2010

    • Author(s)
      田中耕三、伊藤剛、安井明、広田亨
    • Organizer
      第69回日本癌学会学術総会
    • Place of Presentation
      大阪
    • Year and Date
      20100920-22
  • [Presentation] Aurora BはHP1αの動態制御を介し安定した染色体分配を保証する2010

    • Author(s)
      高垣謙太郎、広田亨
    • Organizer
      第27回染色体ワークショップ
    • Place of Presentation
      御殿場
    • Year and Date
      20100120-22
  • [Presentation] ヒト細胞における染色体分離開始とセパレース活性化のタイミング2010

    • Author(s)
      進藤軌久、広田亨
    • Organizer
      第27回染色体ワークショップ
    • Place of Presentation
      御殿場
    • Year and Date
      20100120-22
  • [Presentation] Visualization of separase activity defines the activation timing at the metaphase-to-anaphase transition2010

    • Author(s)
      Shindo, N., Hirota, T.
    • Organizer
      Annual meeting of American Society of Cell Biology
    • Place of Presentation
      Philadelphia
    • Year and Date
      2010-12-11
  • [Presentation] How chromosomes are assembled in cells entering mitosis2010

    • Author(s)
      Hirota, T.
    • Organizer
      The MEXT Priority Research International Symposium Mitosis
    • Place of Presentation
      Tokyo
    • Year and Date
      2010-11-08
  • [Presentation] 染色体分離の瞬間を規定するメカニズム2010

    • Author(s)
      広田亨
    • Organizer
      かずさDNA研究所・セミナー
    • Place of Presentation
      木更津
    • Year and Date
      2010-09-17
  • [Presentation] ヒト細胞における染色体の分配機構2010

    • Author(s)
      広田亨
    • Organizer
      国立がん研究センター研究所・セミナー
    • Place of Presentation
      東京
    • Year and Date
      2010-05-28
  • [Presentation] Toward targeting chromosome segregation machinery for cancer therapeutics2010

    • Author(s)
      Hirota, T
    • Organizer
      8th Annual meeting of Japanese Society of Medical Oncology
    • Place of Presentation
      Tokyo
    • Year and Date
      2010-03-29
  • [Presentation] Kinetochore stretching promotes the metaphase-to-anaphase transition2009

    • Author(s)
      Hirota, T. Uchida K. S. K
    • Organizer
      FASEB Meeting Mitosis : Spindle assembly and function
    • Place of Presentation
      Lucca
    • Year and Date
      20090830-0904
  • [Presentation] Kinetochore stretching promotes the metaphase-to-anaphase transition2009

    • Author(s)
      Hirota, T
    • Organizer
      61st Annual Meeting of the Japanese Society for Cell Biology
    • Place of Presentation
      Nagoya
    • Year and Date
      20090602-04
  • [Presentation] How mammalian cells trigger chromosome segregation at the correct time2009

    • Author(s)
      Hirota, T
    • Organizer
      Seminar at European Molecular Biology Laboratories
    • Place of Presentation
      Heidelberg
    • Year and Date
      2009-11-23
  • [Presentation] ヒト細胞における染色体分離の制御2009

    • Author(s)
      広田亨
    • Organizer
      東京大学医科学研究所. GCOE特別セミナー
    • Place of Presentation
      東京
    • Year and Date
      2009-11-08
  • [Presentation] How chromosomes segregation is triggered in human cells2009

    • Author(s)
      Hirota, T
    • Organizer
      Seminar at Eidgenossische Technische Hochschule Zurich
    • Place of Presentation
      Zurich
    • Year and Date
      2009-08-28
  • [Presentation] Chromosome segregation machinery2009

    • Author(s)
      Hirota, T., Kishimoto, T. Organizer
    • Organizer
      The MEXT Priority Research International Workshop
    • Place of Presentation
      Tokyo
    • Year and Date
      2009-06-05
  • [Book] Mitosis and Meiosis : Molecular Control of Chromosome Separation. Review Encyclopedia of Life Sciences2011

    • Author(s)
      Nagasaka, K., Gallego-Paez, L. M., Hirota, T
  • [Book] Separase. Review. Handbook of Proteolytic Enzymes 3rd Edition2011

    • Author(s)
      Kumada, K., Hirota, T
  • [Book] 紡錘体形成チェックポイント2010

    • Author(s)
      広田亨
    • Total Pages
      862-867
    • Publisher
      細胞工学
  • [Book] 紡錘体形成チェックポイント2010

    • Author(s)
      広田亨
    • Total Pages
      94-101
    • Publisher
      東京、共立出版
  • [Book] ヒストンのリン酸化によるクロマチンの制御2009

    • Author(s)
      広田亨、進藤軌久
    • Total Pages
      1353-1358
    • Publisher
      実験医学
  • [Remarks]

    • URL

      http://www.jfcr.or.jp/tci/exppathol/index.html

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Published: 2013-07-31  

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