title: Protein Recognition in Drug-Induced DNA Alkylation: When the Moonlight Protein GAPDH Meets S23906-1/DNA Minor Groove Adducts.
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.
authors.affiliation: 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. gaelle.lenglet@u-picardie.fr.
authors.forename: Gaëlle
authors.initials: G
authors.lastname: Savreux-Lenglet
authors.affiliation: 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. sabine.depauw@inserm.fr.
authors.forename: Sabine
authors.initials: S
authors.lastname: Depauw
authors.affiliation: 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. marie-helene.david@inserm.fr.
authors.forename: Marie-Hélène
authors.initials: MH
authors.lastname: David-Cordonnier
mesh_terms: D000477:Alkylating Agents / Q000494:pharmacology*; D000478:Alkylation; D002467:Cell Nucleus; D003593:Cytoplasm; D004247:DNA / Q000737:chemistry* / Q000378:metabolism*; D018736:DNA Adducts / Q000378:metabolism*; D004249:DNA Damage; D004261:DNA Replication; D004268:DNA-Binding Proteins / Q000378:metabolism*; D024581:Glyceraldehyde-3-Phosphate Dehydrogenase (Phosphorylating) / Q000378:metabolism; D009690:Nucleic Acid Conformation; D011485:Protein Binding; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D000477:Alkylating Agents; D018736:DNA Adducts; D004268:DNA-Binding Proteins; D014157:Transcription Factors; D004247:DNA; D024581:Glyceraldehyde-3-Phosphate Dehydrogenase (Phosphorylating)
keywords: DNA alkylation; DNA repair; Glyceraldehyde-3-phosphate dehydrogenase; S23906-1; protein/DNA binding