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The role of MCPH1, a protein responsible for primary microcephaly, in chromosome condensation

Research Project

Project/Area Number 21770196
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeSingle-year Grants
Research Field Molecular biology
Research InstitutionThe Institute of Physical and Chemical Research

Principal Investigator

YAMASHITA Daisuke  独立行政法人理化学研究所, 平野染色体ダイナミクス研究室, 基礎科学特別研究員 (50462742)

Project Period (FY) 2009 – 2011
Project Status Completed (Fiscal Year 2011)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2011: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2010: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2009: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
KeywordsMCPH1 / 染色体凝縮 / コンデンシン / 小頭症 / カエル卵抽出液 / 進化 / コンデンシンII
Research Abstract

Mutations in human MCPH1(hMCPH1) cause primary microcephaly, which is characterized by a marked reduction of brain size. hMCPH1 mutant patient cells display unique cellular phenotypes, including premature chromosome condensation(PCC), in G2 phase. To examine a role of MCPH1 in chromosome condensation, I developed a cell-free assay using Xenopus egg extracts. The results demonstrated that an N-terminal domain of hMCPH1 specifically inhibits the action of condensin II in vitro. A complementation assay using patient cells revealed that the N-terminal domain of hMCPH1 is sufficient to rescue the PCC phenotype. Thus, hMCPH1 acts as a direct modulator of condensin II to regulate chromosome condensation.

Report

(4 results)
  • 2011 Annual Research Report   Final Research Report ( PDF )
  • 2010 Annual Research Report
  • 2009 Annual Research Report
  • Research Products

    (8 results)

All 2012 2011 2010

All Journal Article (4 results) (of which Peer Reviewed: 4 results) Presentation (4 results)

  • [Journal Article] MCPH1 regulates chromosome condensation and shaping as a composite modulator of condensin II2011

    • Author(s)
      Yamashita D., Shintomi K., Ono T., Gavvovidis I., Schindler D., Neitzel H., Trimborn M., and Hirano T.
    • Journal Title

      J. Cell Biol

      Volume: 194 Pages: 841-854

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] MCPH1 regulates chromosome condensation and shaping as a composite modulator of condensin II2011

    • Author(s)
      D.Yamashita
    • Journal Title

      J.Cell Biol.

      Volume: 194 Issue: 6 Pages: 841-854

    • DOI

      10.1083/jcb.201106141

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] MCPH1 patient cells exhibit delayed release from DNA damage-induced G2/M checkpoint arrest2010

    • Author(s)
      Gavvovidis I., Pohlmann C., Marchal JA., Stumm M., Yamashita D., Hirano T., Schindler D., Neitzel H., and Trimborn M.
    • Journal Title

      Cell Cycle

      Volume: 9 Pages: 4893-4899

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] MCPH1 patient cells exhibit delayed release from DNA damage-induced G2/M checkpoint arrest.2010

    • Author(s)
      Ioannis Gavvovidis
    • Journal Title

      Cell Cycle

      Volume: 9 Pages: 4893-9

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Presentation] 小頭症の原因タンパク質MCPH1によるコンデンシンIIの制御2012

    • Author(s)
      山下大輔、新冨圭史、小野教夫、Gavvovidis I.、Schindler D.、Neitzel H.、Trimborn M.、平野達也
    • Organizer
      第29回染色体ワークショップ
    • Place of Presentation
      仙台
    • Year and Date
      2012-01-26
    • Related Report
      2011 Final Research Report
  • [Presentation] 小頭症の原因タンパク質MCPH1によるコンデンシンIIの制御2012

    • Author(s)
      山下大輔, 他
    • Organizer
      第29回染色体ワークショップ
    • Place of Presentation
      ホテルニュー水戸屋(仙台)
    • Year and Date
      2012-01-26
    • Related Report
      2011 Annual Research Report
  • [Presentation] 小頭症の原因タンパク質MCPH1によるコンデンシンIIの制御2010

    • Author(s)
      山下大輔、新冨圭史、小野教夫、平野達也
    • Organizer
      第33回日本分子生物学会年会、第83回日本生化学会大会合同大会
    • Place of Presentation
      神戸
    • Year and Date
      2010-12-07
    • Related Report
      2011 Final Research Report
  • [Presentation] 小頭症の原因タンパク質MCPH1によるコンデンシンIIの制御2010

    • Author(s)
      山下大輔
    • Organizer
      BMB2010(第33回日本分子生物学会年会、第83回日本生化学会大会合同大会)
    • Place of Presentation
      神戸
    • Year and Date
      2010-12-07
    • Related Report
      2010 Annual Research Report

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Published: 2009-04-01   Modified: 2016-04-21  

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