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Open AccessArticle

Molecular Determinant of DIDS Analogs Targeting RAD51 Activity

by Denis Velic, Alexandre Demeyer, Thibaut Peterlini, Houda Benhelli-Mokrani, Monique Mathé-Allainmat, Jean-Yves Masson and Fabrice Fleury

Molecules 2021, 26(18), 5460; https://doi.org/10.3390/molecules26185460 - 8 Sep 2021

Cited by 9 | Viewed by 3209

Abstract

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. Full article

(This article belongs to the Special Issue DNA Damage and Repair)

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10 pages, 538 KiB

Open AccessCommunication

by Steeve H. Thany, Céline M. Bourdin, Jérôme Graton, Adèle D. Laurent, Monique Mathé-Allainmat, Jacques Lebreton and Jean-Yves Le Questel

Insects 2015, 6(4), 805-814; https://doi.org/10.3390/insects6040805 - 28 Sep 2015

Cited by 24 | Viewed by 5576

Abstract

In the present study, the effects of low (10 ng/bee) and high (100 ng/bee) doses of acetamiprid and deltamethrin insecticides on multi-trial learning and retrieval were evaluated in the honey bee Apis mellifera. After oral application, acetamiprid and deltamethrin at the concentrations used were not able to impair learning sessions. When the retention tests were performed 1 h, 6 h, and 24 h after learning, we found a significant difference between bees after learning sessions when drugs were applied 24 h before learning. Deltamethrin-treated bees were found to be more sensitive at 10 ng/bee and 100 ng/bee doses compared to acetamiprid-treated bees, only with amounts of 100 ng/bee and at 6 h and 24 h delays. When insecticides were applied during learning sessions, none of the tested insecticides was able to impair learning performance at 10 ng/bee or 100 ng/bee but retention performance was altered 24 h after learning sessions. Acetamiprid was the only one to impair retrieval at 10 ng/bee, whereas at 100 ng/bee an impairment of retrieval was found with both insecticides. The present results therefore suggest that acetamiprid and deltamethrin are able to impair retrieval performance in the honey bee Apis mellifera. Full article

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