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Molecular Determinant of DIDS Analogs Targeting RAD51 Activity

Mechanism and Regulation of DNA Repair Team, UFIP, UMR 6286 CNRS, University of Nantes, F-44000 Nantes, France
Genome Stability Laboratory, CHU de Québec Research Center, HDQ Pavilion, Oncology Division, 9 McMahon, Québec City, QC G1R 3S3, Canada
Department of Molecular Biology, Medical Biochemistry, and Pathology, Laval University Cancer Research Center, Québec City, QC G1V 0A6, Canada
CEISAM, UMR 6230 CNRS, University of Nantes, F-44000 Nantes, France
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Academic Editors: Daniel Roca-Sanjuán, Virginie L. Lhiaubet-Vallet and Iñaki Tuñón
Molecules 2021, 26(18), 5460;
Received: 30 July 2021 / Revised: 1 September 2021 / Accepted: 3 September 2021 / Published: 8 September 2021
(This article belongs to the Special Issue DNA Damage and Repair)
RAD51 is the central protein in DNA repair by homologous recombination (HR), involved in several steps of this process. It is shown that overexpression of the RAD51 protein is correlated with increased survival of cancer cells to cancer treatments. For the past decade, RAD51 overexpression-mediated resistance has justified the development of targeted inhibitors. One of the first molecules described to inhibit RAD51 was the 4,4′-diisothiocyanato-stilbene-2,2′-disulfonic acid (DIDS) molecule. This small molecule is effective in inhibiting different functions of RAD51, however its mode of action and the chemical functions involved in this inhibition have not been identified. In this work, we used several commercial molecules derived from DIDS to characterize the structural determinants involved in modulating the activity of RAD51. By combining biochemical and biophysical approaches, we have shown that DIDS and two analogs were able to inhibit the binding of RAD51 to ssDNA and prevent the formation of D-loop by RAD51. Both isothiocyanate substituents of DIDS appear to be essential in the inhibition of RAD51. These results open the way to the synthesis of new molecules derived from DIDS that should be greater modulators of RAD51 and more efficient for HR inhibition. View Full-Text
Keywords: RAD51; recombinase activity; inhibitor; stilbene derivatives; cancer RAD51; recombinase activity; inhibitor; stilbene derivatives; cancer
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MDPI and ACS Style

Velic, D.; Demeyer, A.; Peterlini, T.; Benhelli-Mokrani, H.; Mathé-Allainmat, M.; Masson, J.-Y.; Fleury, F. Molecular Determinant of DIDS Analogs Targeting RAD51 Activity. Molecules 2021, 26, 5460.

AMA Style

Velic D, Demeyer A, Peterlini T, Benhelli-Mokrani H, Mathé-Allainmat M, Masson J-Y, Fleury F. Molecular Determinant of DIDS Analogs Targeting RAD51 Activity. Molecules. 2021; 26(18):5460.

Chicago/Turabian Style

Velic, Denis, Alexandre Demeyer, Thibaut Peterlini, Houda Benhelli-Mokrani, Monique Mathé-Allainmat, Jean-Yves Masson, and Fabrice Fleury. 2021. "Molecular Determinant of DIDS Analogs Targeting RAD51 Activity" Molecules 26, no. 18: 5460.

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