Halenaquinone, a chemical compound that specifically inhibits the secondary DNA binding of RAD51

Motoki Takaku, Takashi Kainuma, Takako Ishida-Takaku, Shintaro Ishigami, Hidekazu Suzuki, Satoshi Tashiro, Rob W M van Soest, Youichi Nakao, Hitoshi Kurumizaka

    Research output: Contribution to journalArticle

    27 Citations (Scopus)

    Abstract

    Mutations and single-nucleotide polymorphisms affecting RAD51 gene function have been identified in several tumors, suggesting that the inappropriate expression of RAD51 activity may cause tumorigenesis. RAD51 is an essential enzyme for the homologous recombinational repair (HRR) of DNA double-strand breaks. In the HRR pathway, RAD51 catalyzes the homologous pairing between single-stranded DNA (ssDNA) and double-stranded DNA (dsDNA), which is the central step of the HRR pathway. To identify a chemical compound that regulates the homologous-pairing activity of RAD51, in the present study, we screened crude extract fractions from marine sponges by the RAD51-mediated homologous-pairing assay. Halenaquinone was identified as an inhibitor of the RAD51 homologous-pairing activity. A surface plasmon resonance analysis indicated that halenaquinone directly bound to RAD51. Intriguingly, halenaquinone specifically inhibited dsDNA binding by RAD51 alone or the RAD51-ssDNA complex, but only weakly affected the RAD51-ssDNA binding. In vivo, halenaquinone significantly inhibited the retention of RAD51 at double-strand break sites. Therefore, halenaquinone is a novel type of RAD51 inhibitor that specifically inhibits the RAD51-dsDNA binding.

    Original languageEnglish
    Pages (from-to)427-436
    Number of pages10
    JournalGenes to Cells
    Volume16
    Issue number4
    DOIs
    Publication statusPublished - 2011 Apr

    Fingerprint

    Recombinational DNA Repair
    Single-Stranded DNA
    Surface Plasmon Resonance
    DNA
    Porifera
    Complex Mixtures
    Single Nucleotide Polymorphism
    Carcinogenesis
    halenaquinone
    Mutation
    Enzymes
    Genes
    Neoplasms

    ASJC Scopus subject areas

    • Genetics
    • Cell Biology

    Cite this

    Takaku, M., Kainuma, T., Ishida-Takaku, T., Ishigami, S., Suzuki, H., Tashiro, S., ... Kurumizaka, H. (2011). Halenaquinone, a chemical compound that specifically inhibits the secondary DNA binding of RAD51. Genes to Cells, 16(4), 427-436. https://doi.org/10.1111/j.1365-2443.2011.01494.x

    Halenaquinone, a chemical compound that specifically inhibits the secondary DNA binding of RAD51. / Takaku, Motoki; Kainuma, Takashi; Ishida-Takaku, Takako; Ishigami, Shintaro; Suzuki, Hidekazu; Tashiro, Satoshi; van Soest, Rob W M; Nakao, Youichi; Kurumizaka, Hitoshi.

    In: Genes to Cells, Vol. 16, No. 4, 04.2011, p. 427-436.

    Research output: Contribution to journalArticle

    Takaku, M, Kainuma, T, Ishida-Takaku, T, Ishigami, S, Suzuki, H, Tashiro, S, van Soest, RWM, Nakao, Y & Kurumizaka, H 2011, 'Halenaquinone, a chemical compound that specifically inhibits the secondary DNA binding of RAD51', Genes to Cells, vol. 16, no. 4, pp. 427-436. https://doi.org/10.1111/j.1365-2443.2011.01494.x
    Takaku, Motoki ; Kainuma, Takashi ; Ishida-Takaku, Takako ; Ishigami, Shintaro ; Suzuki, Hidekazu ; Tashiro, Satoshi ; van Soest, Rob W M ; Nakao, Youichi ; Kurumizaka, Hitoshi. / Halenaquinone, a chemical compound that specifically inhibits the secondary DNA binding of RAD51. In: Genes to Cells. 2011 ; Vol. 16, No. 4. pp. 427-436.
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    abstract = "Mutations and single-nucleotide polymorphisms affecting RAD51 gene function have been identified in several tumors, suggesting that the inappropriate expression of RAD51 activity may cause tumorigenesis. RAD51 is an essential enzyme for the homologous recombinational repair (HRR) of DNA double-strand breaks. In the HRR pathway, RAD51 catalyzes the homologous pairing between single-stranded DNA (ssDNA) and double-stranded DNA (dsDNA), which is the central step of the HRR pathway. To identify a chemical compound that regulates the homologous-pairing activity of RAD51, in the present study, we screened crude extract fractions from marine sponges by the RAD51-mediated homologous-pairing assay. Halenaquinone was identified as an inhibitor of the RAD51 homologous-pairing activity. A surface plasmon resonance analysis indicated that halenaquinone directly bound to RAD51. Intriguingly, halenaquinone specifically inhibited dsDNA binding by RAD51 alone or the RAD51-ssDNA complex, but only weakly affected the RAD51-ssDNA binding. In vivo, halenaquinone significantly inhibited the retention of RAD51 at double-strand break sites. Therefore, halenaquinone is a novel type of RAD51 inhibitor that specifically inhibits the RAD51-dsDNA binding.",
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