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Updated: Oct 18, 2025
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Real-time Observation of the DNA Strand Exchange Reaction Mediated by Rad51
Published on: February 13, 2019
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Molecular Determinant of DIDS Analogs Targeting RAD51 Activity
Denis Velic1,2,3, Alexandre Demeyer1, Thibaut Peterlini2,3
1Mechanism and Regulation of DNA Repair Team, UFIP, UMR 6286 CNRS, University of Nantes, F-44000 Nantes, France.
Molecules (Basel, Switzerland)
|September 28, 2021
Summary
The study identified that the isothiocyanate groups in the DIDS molecule are crucial for inhibiting RAD51, a protein involved in DNA repair and cancer cell survival. This finding aids in developing new RAD51 inhibitors for cancer therapy.
Area of Science:
- Molecular Biology
- Biochemistry
- Structural Biology
Background:
- RAD51 is a key protein in DNA repair via homologous recombination (HR).
- Overexpression of RAD51 promotes cancer cell survival and resistance to treatments.
- Targeted RAD51 inhibitors are being developed to overcome this resistance.
Purpose of the Study:
- To identify the structural determinants of 4,4'-diisothiocyanato-stilbene-2,2'-disulfonic acid (DIDS) responsible for inhibiting RAD51.
- To understand the mechanism by which DIDS and its analogs affect RAD51 function.
Main Methods:
- Utilized commercial DIDS derivatives.
- Employed biochemical and biophysical approaches.
- Assessed RAD51 binding to single-stranded DNA (ssDNA) and D-loop formation.
Main Results:
- DIDS and two analogs inhibited RAD51 binding to ssDNA.
- These molecules prevented RAD51-mediated D-loop formation.
- The isothiocyanate substituents of DIDS were essential for RAD51 inhibition.
Conclusions:
- The isothiocyanate groups are critical for DIDS's inhibitory activity on RAD51.
- These findings facilitate the design of novel, more potent RAD51 inhibitors.
- This research advances the development of targeted therapies for HR-deficient cancers.
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