DIDS, a chemical compound that inhibits RAD51-mediated homologous pairing and strand exchange

Takako Ishida, Yoshimasa Takizawa, Takashi Kainuma, Jin Inoue, Tsutomu Mikawa, Takehiko Shibata, Hidekazu Suzuki, Satoshi Tashiro, Hitoshi Kurumizaka

    Research output: Contribution to journalArticle

    38 Citations (Scopus)

    Abstract

    RAD51, an essential eukaryotic DNA recombinase, promotes homologous pairing and strand exchange during homologous recombination and the recombinational repair of double strand breaks. Mutations that up- or down-regulate RAD51 gene expression have been identified in several tumors, suggesting that inappropriate expression of the RAD51 activity may cause tumorigenesis. To identify chemical compounds that affect the RAD51 activity, in the present study, we performed the RAD51-mediated strand exchange assay in the presence of 185 chemical compounds. We found that 4,4′-diisothiocyanostilbene-2,2′-disulfonic acid (DIDS) efficiently inhibited the RAD51-mediated strand exchange. DIDS also inhibited the RAD51-mediated homologous pairing in the absence of RPA. A surface plasmon resonance analysis revealed that DIDS directly binds to RAD51. A gel mobility shift assay showed that DIDS significantly inhibited the DNA-binding activity of RAD51. Therefore, DIDS may bind near the DNA binding site(s) of RAD51 and compete with DNA for RAD51 binding.

    Original languageEnglish
    Pages (from-to)3367-3376
    Number of pages10
    JournalNucleic Acids Research
    Volume37
    Issue number10
    DOIs
    Publication statusPublished - 2009

    Fingerprint

    Acids
    Recombinational DNA Repair
    DNA
    Recombinases
    Surface Plasmon Resonance
    Electrophoretic Mobility Shift Assay
    Carcinogenesis
    Up-Regulation
    Down-Regulation
    Gels
    Binding Sites
    Gene Expression
    Mutation
    Neoplasms

    ASJC Scopus subject areas

    • Genetics

    Cite this

    Ishida, T., Takizawa, Y., Kainuma, T., Inoue, J., Mikawa, T., Shibata, T., ... Kurumizaka, H. (2009). DIDS, a chemical compound that inhibits RAD51-mediated homologous pairing and strand exchange. Nucleic Acids Research, 37(10), 3367-3376. https://doi.org/10.1093/nar/gkp200

    DIDS, a chemical compound that inhibits RAD51-mediated homologous pairing and strand exchange. / Ishida, Takako; Takizawa, Yoshimasa; Kainuma, Takashi; Inoue, Jin; Mikawa, Tsutomu; Shibata, Takehiko; Suzuki, Hidekazu; Tashiro, Satoshi; Kurumizaka, Hitoshi.

    In: Nucleic Acids Research, Vol. 37, No. 10, 2009, p. 3367-3376.

    Research output: Contribution to journalArticle

    Ishida, T, Takizawa, Y, Kainuma, T, Inoue, J, Mikawa, T, Shibata, T, Suzuki, H, Tashiro, S & Kurumizaka, H 2009, 'DIDS, a chemical compound that inhibits RAD51-mediated homologous pairing and strand exchange', Nucleic Acids Research, vol. 37, no. 10, pp. 3367-3376. https://doi.org/10.1093/nar/gkp200
    Ishida, Takako ; Takizawa, Yoshimasa ; Kainuma, Takashi ; Inoue, Jin ; Mikawa, Tsutomu ; Shibata, Takehiko ; Suzuki, Hidekazu ; Tashiro, Satoshi ; Kurumizaka, Hitoshi. / DIDS, a chemical compound that inhibits RAD51-mediated homologous pairing and strand exchange. In: Nucleic Acids Research. 2009 ; Vol. 37, No. 10. pp. 3367-3376.
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    abstract = "RAD51, an essential eukaryotic DNA recombinase, promotes homologous pairing and strand exchange during homologous recombination and the recombinational repair of double strand breaks. Mutations that up- or down-regulate RAD51 gene expression have been identified in several tumors, suggesting that inappropriate expression of the RAD51 activity may cause tumorigenesis. To identify chemical compounds that affect the RAD51 activity, in the present study, we performed the RAD51-mediated strand exchange assay in the presence of 185 chemical compounds. We found that 4,4′-diisothiocyanostilbene-2,2′-disulfonic acid (DIDS) efficiently inhibited the RAD51-mediated strand exchange. DIDS also inhibited the RAD51-mediated homologous pairing in the absence of RPA. A surface plasmon resonance analysis revealed that DIDS directly binds to RAD51. A gel mobility shift assay showed that DIDS significantly inhibited the DNA-binding activity of RAD51. Therefore, DIDS may bind near the DNA binding site(s) of RAD51 and compete with DNA for RAD51 binding.",
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