title: DNA Damage-inducing Compounds: Unraveling their Pleiotropic Effects Using High Throughput Sequencing.
abstract: Compounds causing DNA damage have been used widely in molecular biology and some are used as therapeutic agents in cancer therapy. In most cases, their cellular response is pleiotropic, making it challenging to develop these agents efficiently for potential therapeutic use. Furthermore, this means that such compounds can also affect healthy tissues, which is a major drawback for the use in therapy. Thus, dissecting and understanding not only their molecular mode of action, but also identifying all their cellular targets is critical. With the advent of high throughput DNA sequencing technologies our understanding of the genomic targets of such compounds has increased significantly over recent years. This review gives an overview of some well-studied DNA-damaging agents and dissects what is known about their molecular mode of action, their cellular response and use in clinical settings. It then describes how high throughput-sequencing approaches can be used (a) to study DNAdamaging compounds and (b) to gain insight into their biological activity in vivo.
authors.affiliation: Institut Curie, PSL Research University, Organic Synthesis and Cell Biology Group, CNRS UMR3666, INSERM U1143, 26 rue d'Ulm, 75248 Paris Cedex 05. France.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Müller
mesh_terms: D000477:Alkylating Agents / Q000627:therapeutic use / Q000633:toxicity; D000970:Antineoplastic Agents / Q000627:therapeutic use / Q000633:toxicity*; D004249:DNA Damage / Q000187:drug effects; D004260:DNA Repair; D026942:DNA Topoisomerases / Q000737:chemistry / Q000378:metabolism; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy / Q000473:pathology; D054852:Small Molecule Libraries / Q000737:chemistry / Q000627:therapeutic use / Q000633:toxicity
chemical_list: D000477:Alkylating Agents; D000970:Antineoplastic Agents; D054852:Small Molecule Libraries; D026942:DNA Topoisomerases
keywords: DDR; DNA damage; chemical biology; drug; next generation sequencing; sequencing; small molecule