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2010 Fiscal Year Final Research Report

Screening and analyses of novel BRCA1/2-associated proteins

Research Project

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Project/Area Number 21790311
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeSingle-year Grants
Research Field Pathological medical chemistry
Research InstitutionTokyo Medical and Dental University

Principal Investigator

TAKENAKA Katsuya  Tokyo Medical and Dental University, 難治疾患研究所, 助教 (20378706)

Project Period (FY) 2009 – 2010
Keywords分子腫瘍学
Research Abstract

BRCA2 germline mutations account for the majority of heredity breast and ovarian cancer. Besides its role in DNA damage repair, it was hypothesized that BRCA2 might have a role in centrosomal amplification, since BRCA2 localizes to centrosomes as well as nuclei and the dysfunction of BRCA2 in a centrosome causes abnormalities in cell division. We identified nucleophosmin (NPM) and Rho-associated coiled-coil containing protein kinase 2 (ROCK2) as novel BRCA2-associated proteins by mass spectrometry. Because it is known that ROCK2 binds to NPM at centrosomes, these 3 proteins may form a complex. NPM-binding region in BRCA2 was determined to be within amino acids 639-1,000. Exogenous expression of this BRCA2 region resulted in aberrant centrosome amplification and a high frequency of multinucleated cells. Our results suggested that a complex consisting of BRCA2, NPM, and ROCK2 maintains the numerical integrity of centrosomes and accurate cell division and that dysfunction of this regulation might be involved in the tumorigenesis of breast cancer.

  • Research Products

    (12 results)

All 2010 2009

All Journal Article (5 results) (of which Peer Reviewed: 5 results) Presentation (7 results)

  • [Journal Article] BRCA2 and nucleophosmin coregulate centrosome amplification and form a complex with ROCK2.2010

    • Author(s)
      Hui-Feng Wang, Katsuya Takenaka, Akira Nakanishi, Yoshio Miki.
    • Journal Title

      Cancer Research 71

      Pages: 68-77

    • Peer Reviewed
  • [Journal Article] Three DNA polymerases, recruited by different mechanisms, carry out NER repair synthesis in human cells.2010

    • Author(s)
      Tomoo Ogi, Siripan Limsirichaikul^+, Ren M.Overmeer^+, Marcel Volker^+, Katsuya Takenaka^+, Ross Cloney^+, Yuka Nakazawa^+, Atsuko Niimi, Yoshio Miki, Nicolaas G.Jaspers, Leon H.F.Mullenders, Shunichi Yamashita, Maria I.Fousteri, Alan R.Lehmann.
    • Journal Title

      Molecular Cell 37

      Pages: 714-727

    • Peer Reviewed
  • [Journal Article] PTIP promotes DNA double-strand break repair through homologous recombination.2010

    • Author(s)
      Xin Wang, Katsuya Takenaka, Shunichi Takeda.
    • Journal Title

      Genes to Cells 15

      Pages: 243-254

    • Peer Reviewed
  • [Journal Article] Introduction and characterization of a polymerase-dead point mutation into the POLK gene in vertebrates.2009

    • Author(s)
      Katsuya, Takenaka, Yoshio Miki.
    • Journal Title

      FEBS Letters 583

      Pages: 661-664

    • Peer Reviewed
  • [Journal Article] Genetic evidence for single-strand lesions initiating Nbs1-dependent homologous recombination in diversification of Ig V in chicken B lymphocytes.2009

    • Author(s)
      Makoto Nakahara, Eiichiro Sonoda, Kuniharu Nojima, Julian E.Sale, Katsuya Takenaka, Koji Kikuchi, Yoshihito Taniguchi, Kyoko Nakamura, Yoshiki Sumitomo, Ronan T.Bree, Noel F.Lowndes, Shunichi Takeda.
    • Journal Title

      PLoS Genetics 5

      Pages: 1000356

    • Peer Reviewed
  • [Presentation] BRCA2 and nucleophosmin coregulate centrosome amplification and form a complex with2010

    • Author(s)
      Katsuya Takenaka, Hui-Feng Wang, Akira Nakanishi, Yoshio Miki.
    • Organizer
      ROCK2.BMB2010
    • Place of Presentation
      Kobe
    • Year and Date
      20101207-20101210
  • [Presentation] BRCA2 and nucleophosmin coregulate centrosome amplification and form a complex with ROCK2.2010

    • Author(s)
      Hui-Feng Wang, Katsuya Takenaka, Akira Nakanishi, Yoshio Miki.
    • Organizer
      The Sixth International Symposium on Hormononmonnium on Hormonal Oncogenesis
    • Place of Presentation
      Urayasu
    • Year and Date
      20100912-20100916
  • [Presentation] Introduction and characterization of a polymerase-dead point mutation into the POLK gene in vertebrates.2010

    • Author(s)
      Katsuya Takenaka, Yoshio Miki.
    • Organizer
      International Conference on Radiation and Cancer Biology at Nagasaki 2010
    • Place of Presentation
      Nagasaki
    • Year and Date
      20100217-20100220
  • [Presentation] Three DNA polymerases, recruited by different mechanisms, carry out NER repair synthesis in human cells.2010

    • Author(s)
      Tomoo Ogi, Siripan Limsirichaikul, Ren M. Overmeer, Marcel Volker, Katsuya Takenaka, Ross Cloney, Yuka Nakazawa, Atsuko Niimi, Yoshio Miki, Nicolaas G., Jaspers, Leon H.F., Mullenders, Shunichi Yamashita, Maria I., Fousteri, Alan R.Lehmann.
    • Organizer
      International Conference on Radiation and Cancer Biology at Nagasaki 2010
    • Place of Presentation
      Nagasaki
    • Year and Date
      20100217-20100220
  • [Presentation] Introduction and characterization of a polymerase-dead point mutation into the POLK gene in vertebrates.2009

    • Author(s)
      Katsuya Takenaka, Yoshio Miki.
    • Organizer
      第32回日本分子生物学会年会
    • Place of Presentation
      横浜
    • Year and Date
      20091209-20091212
  • [Presentation] Three DNA polymerases, recruited by different mechanisms, carry out NER repair synthesis in human cells.2009

    • Author(s)
      Tomoo Ogi, Limsirichaikul Siripan, Marcel Volker, Rene Overmeer, Katsuya Takenaka, Ross Cloney, Yuka Nakazawa, Atsuko Niimi, Yoshio Miki, Nicolaas Jaspers, Leon Mullenders, Maria Fousteri, Shunichi Yamashita, Alan Lehmann.
    • Organizer
      第32回日本分子生物学会年会
    • Place of Presentation
      横浜
    • Year and Date
      20091209-20091212
  • [Presentation] ゲノム上点変異導入によるPolκ活性中心変異株の作製と解析2009

    • Author(s)
      竹中克也, 三木義男
    • Organizer
      第82回日本生化学会大会
    • Place of Presentation
      神戸
    • Year and Date
      20091021-20091024

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Published: 2012-02-13   Modified: 2016-04-21  

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