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

40 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 Jun 22
Externally publishedYes

ASJC Scopus subject areas

  • Genetics

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    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, 37(10), 3367-3376. https://doi.org/10.1093/nar/gkp200