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

Takako Ishida1, Yoshimasa Takizawa, Takashi Kainuma

  • 1Laboratory of Structural Biology, Graduate School of Advanced Science and Engineering, Waseda University, 2-2 Wakamatsu-cho, Shinjuku-ku, Tokyo 162-8480, Japan.

Insights

4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS) inhibits RAD51, a key protein in DNA repair and homologous recombination. This compound may disrupt cancer development by interfering with RAD51's DNA binding activity.

Area of Science:

  • Molecular Biology
  • Biochemistry
  • Genetics

Background:

  • RAD51 is a crucial eukaryotic DNA recombinase involved in homologous recombination and DNA double-strand break repair.
  • Aberrant RAD51 gene expression is linked to tumorigenesis, highlighting its importance in cancer development.

Purpose of the Study:

  • To screen for chemical compounds that modulate RAD51 activity.
  • To investigate the inhibitory effects of identified compounds on RAD51-mediated DNA strand exchange and homologous pairing.

Main Methods:

  • RAD51-mediated strand exchange assay with 185 chemical compounds.
  • Surface plasmon resonance (SPR) analysis to detect direct binding.
  • Gel mobility shift assay to assess DNA-binding activity.

Main Results:

  • 4,4 -diisothiocyanostilbene-2,2 -disulfonic acid (DIDS) was identified as a potent inhibitor of RAD51-mediated strand exchange and homologous pairing.
  • SPR confirmed direct binding of DIDS to RAD51.
  • DIDS significantly inhibited RAD51's DNA-binding activity.

Conclusions:

  • DIDS effectively inhibits RAD51's strand exchange and homologous pairing functions.
  • DIDS likely binds to RAD51 near its DNA-binding site, competing with DNA.
  • DIDS represents a potential therapeutic lead for targeting RAD51 in cancer treatment.

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