The molecular mechanism of the establishment of functional inner centromere

• Project/Area Number: 26440093
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Cell biology
• Research Institution: The University of Tokyo
• Principal Investigator: Tanno Yuji 東京大学, 分子細胞生物学研究所, 助教 (20583123)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2014: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 染色体分配 / セントロメア / 分裂期 / インナーセントロメア / がん

Outline of Final Research Achievements

Frequent chromosome mis-segregation, known as whole chromosomal instability, is the major trait of cancer cells. Previous studies have suggested that chromosomal instability initiates and progresses tumor formation. However, the molecular mechanism of chromosomal instability is to be elucidated. In this project, we clarified that the destabilization of the inner centromere structure, which is formed in between sister kinetochores in mitosis, could be the major cause of chromosomal instability. We also reported that Haspin, a mitotic kinase which establishes inner centromere, localizes at inner centromere through direct interaction with a cohesin-associated protein PDS5. These finding clarified a part of the molecular mechanisms and the physiological significances of the functional inner centromere formation.

Research Products

• [Journal Article] Pds5 Regulates Sister-Chromatid Cohesion and Chromosome Bi-orientation through a Conserved Protein Interaction Module. (2017)
  • Author(s): Goto Y, Yamagishi Y, Shintomi-Kawamura M, Abe M, Tanno Y, Watanabe Y.
  • Journal Title: Current Biology Volume: 印刷中 Issue: 7 Pages: 1005-1012
  • DOI: 10.1016/j.cub.2017.02.066
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Meikin-associated polo-like kinase specifies Bub1 distribution in meiosis I (2017)
  • Author(s): Seira Miyazaki, Jihye Kim, Yuya Yamagishi, Tadashi Ishiguro, Yuki Okada, Yuji Tanno, Takeshi Sakuno and Yoshinori Watanabe
  • Journal Title: Genes to Cells Volume: 印刷中 Issue: 6 Pages: 552-567
  • DOI: 10.1111/gtc.12496
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] The inner centromere-shugoshin network prevents chromosomal instability (2015)
  • Author(s): Tanno Y, Susumu H, Kawamura M, Sugimura H, Honda T, Watanabe Y.
  • Journal Title: Science Volume: 349 Issue: 6253 Pages: 1237-1240
  • DOI: 10.1126/science.aaa2655
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Meikin is a conserved regulator of meiosis-I-specific kinetochore function (2015)
  • Author(s): Kim, J., Ishiguro, K., Nambu, A., Akiyoshi, B., Yokobayashi, S., Kagami, A., Ishiguro, T., Pendas, A.M., Takeda, N., Sakakibara, Y., Kitajima, T.S., Tanno, Y., Sakuno, T., and Watanabe, Y.
  • Journal Title: Nature Volume: 517 Issue: 7535 Pages: 466-471
  • DOI: 10.1038/nature14097
  • Peer Reviewed
• [Journal Article] Targeting condensin, a vital spot of MYCN-amplified neuroblastoma. (2014)
  • Author(s): Tanno Y, Watanabe Y.
  • Journal Title: Cell Cycle Volume: 13 Issue: 8 Pages: 1224-1224
  • DOI: 10.4161/cc.28568
• [Presentation] Destabilization of the inner centromere-shugoshin network causes chromosomal instability (2016)
  • Author(s): Yuji Tanno, Miyuki Shintomi-Kawamura, Hiroaki Susumu and Yoshinori Watanabe
  • Organizer: Centromere Biology, Gordon Research Conference
  • Place of Presentation: Mount Snow, West Dover, VT, USA
  • Year and Date: 2016-07-24
  • Int'l Joint Research
• [Presentation] Destabilization of the Inner Centromere-Shugoshin Network Causes Chromosomal Instability (2016)
  • Author(s): Yuji Tanno
  • Organizer: Centromere Biology (GRS), Gordon-Kenan Research Seminar.
  • Place of Presentation: Mount Snow, West Dover, VT, USA
  • Year and Date: 2016-07-23
  • Int'l Joint Research / Invited
• [Presentation] ICSネットワークの不安定化は染色体不安定性を引き起こす (2016)
  • Author(s): 丹野悠司、新冨(川村)美雪、進寛明、渡邊嘉典
  • Organizer: 第68回日本細胞生物学会大会
  • Place of Presentation: 京都テルサ（京都府京都市）
  • Year and Date: 2016-06-15
• [Presentation] The inner centromere-shugoshin network prevents chromosomal instability (2015)
  • Author(s): Yuji Tanno, Hiroaki Susumu, Miyuki Kawamura and Yoshinori Watanabe
  • Organizer: EMBO Workshop Cell cycle
  • Place of Presentation: Budapest, Hungary
  • Year and Date: 2015-09-04
  • Int'l Joint Research
• [Book] ライフサイエンス 領域融合レビュー インナーセントロメア-シュゴシンネットワークは染色体不安定性をふせぐ (2015)
  • Author(s): 丹野悠司，渡邊嘉典
  • Total Pages: 1
  • Publisher: 大学共同利用機関法人 情報・システム研究機構 ライフサイエンス統合データベースセンター
• [Book] 細胞工学 染色体研究Update 染色体の分配異常とがん (2015)
  • Author(s): 丹野悠司，渡邊嘉典
  • Total Pages: 5
  • Publisher: 学研メディカル秀潤社