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Int. J. Mol. Sci. 2015, 16(11), 26555-26581; doi:10.3390/ijms161125971

Protein Recognition in Drug-Induced DNA Alkylation: When the Moonlight Protein GAPDH Meets S23906-1/DNA Minor Groove Adducts

UMR-S1172—Jean-Pierre Aubert Research Centre (JPARC), INSERM, University of Lille, Lille Hospital, Institut pour la Recherche sur le Cancer de Lille, Place de Verdun F-59045 Lille cedex, France
Current address: U1088 INSERM, Centre Universitaire de Recherche en Santé, CHU Amiens sud, Avenue René Laennec—Salouël, F-80054 Amiens, France.
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Academic Editor: Eric C. Long
Received: 5 August 2015 / Revised: 25 October 2015 / Accepted: 27 October 2015 / Published: 5 November 2015
(This article belongs to the Special Issue Low Molecular Weight DNA and RNA Binding Agents)
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Abstract

DNA alkylating drugs have been used in clinics for more than seventy years. The diversity of their mechanism of action (major/minor groove; mono-/bis-alkylation; intra-/inter-strand crosslinks; DNA stabilization/destabilization, etc.) has undoubtedly major consequences on the cellular response to treatment. The aim of this review is to highlight the variety of established protein recognition of DNA adducts to then particularly focus on glyceraldehyde-3-phosphate dehydrogenase (GAPDH) function in DNA adduct interaction with illustration using original experiments performed with S23906-1/DNA adduct. The introduction of this review is a state of the art of protein/DNA adducts recognition, depending on the major or minor groove orientation of the DNA bonding as well as on the molecular consequences in terms of double-stranded DNA maintenance. It reviews the implication of proteins from both DNA repair, transcription, replication and chromatin maintenance in selective DNA adduct recognition. The main section of the manuscript is focusing on the implication of the moonlighting protein GAPDH in DNA adduct recognition with the model of the peculiar DNA minor groove alkylating and destabilizing drug S23906-1. The mechanism of action of S23906-1 alkylating drug and the large variety of GAPDH cellular functions are presented prior to focus on GAPDH direct binding to S23906-1 adducts. View Full-Text
Keywords: DNA alkylation; DNA repair; Glyceraldehyde-3-phosphate dehydrogenase; S23906-1; protein/DNA binding DNA alkylation; DNA repair; Glyceraldehyde-3-phosphate dehydrogenase; S23906-1; protein/DNA binding
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Savreux-Lenglet, G.; Depauw, S.; David-Cordonnier, M.-H. Protein Recognition in Drug-Induced DNA Alkylation: When the Moonlight Protein GAPDH Meets S23906-1/DNA Minor Groove Adducts. Int. J. Mol. Sci. 2015, 16, 26555-26581.

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