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.
Keywords: DNA damage, DDR, chemical biology, sequencing, next generation sequencing, small molecule, drug.
Current Medicinal Chemistry
Title:DNA Damage-inducing Compounds: Unraveling their Pleiotropic Effects Using High Throughput Sequencing
Volume: 24 Issue: 15
Author(s): Sebastian Müller*
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
Keywords: DNA damage, DDR, chemical biology, sequencing, next generation sequencing, small molecule, drug.
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.
Export Options
About this article
Cite this article as:
Müller Sebastian*, DNA Damage-inducing Compounds: Unraveling their Pleiotropic Effects Using High Throughput Sequencing, Current Medicinal Chemistry 2017; 24 (15) . https://dx.doi.org/10.2174/0929867324666170124143710
DOI https://dx.doi.org/10.2174/0929867324666170124143710 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
Call for Papers in Thematic Issues
Advances in Medicinal Chemistry: From Cancer to Chronic Diseases.
The broad spectrum of the issue will provide a comprehensive overview of emerging trends, novel therapeutic interventions, and translational insights that impact modern medicine. The primary focus will be diseases of global concern, including cancer, chronic pain, metabolic disorders, and autoimmune conditions, providing a broad overview of the advancements in ...read more
Approaches to the treatment of chronic inflammation
Chronic inflammation is a hallmark of numerous diseases, significantly impacting global health. Although chronic inflammation is a hot topic, not much has been written about approaches to its treatment. This thematic issue aims to showcase the latest advancements in chronic inflammation treatment and foster discussion on future directions in this ...read more
Cellular and Molecular Mechanisms of Non-Infectious Inflammatory Diseases: Focus on Clinical Implications
The Special Issue covers the results of the studies on cellular and molecular mechanisms of non-infectious inflammatory diseases, in particular, autoimmune rheumatic diseases, atherosclerotic cardiovascular disease and other age-related disorders such as type II diabetes, cancer, neurodegenerative disorders, etc. Review and research articles as well as methodology papers that summarize ...read more
Chalcogen-modified nucleic acid analogues
Chalcogen-modified nucleosides, nucleotides and oligonucleotides have been of great interest to scientific research for many years. The replacement of oxygen in the nucleobase, sugar or phosphate backbone by chalcogen atoms (sulfur, selenium, tellurium) gives these biomolecules unique properties resulting from their altered physical and chemical properties. The continuing interest in ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Protein Misfolding and Misprocessing in Complex Disease
Protein & Peptide Letters Structure and Expression of Different Serum Amyloid A (SAA) Variants and their Concentration-Dependent Functions During Host Insults
Current Medicinal Chemistry The Potential of Ellagic Acid as a Possible Antimalarial Drug Candidate
Current Bioactive Compounds Viral and Non-Viral Approaches for Transient Delivery of mRNA and Proteins
Current Gene Therapy FHIT and p53 Status and Response to Platinum-Based Treatment in Advanced Non-Small Cell Lung Cancer
Current Cancer Drug Targets Chirality - A New Era of Therapeutics
Mini-Reviews in Medicinal Chemistry Overview of Cantharidin and its Analogues
Current Medicinal Chemistry Mechanisms of Action of DNA-Damaging Anticancer Drugs in Treatment of Carcinomas: Is Acute Apoptosis an “Off-Target” Effect?
Mini-Reviews in Medicinal Chemistry Nuclear Export Mediated Regulation of MicroRNAs: Potential Target for Drug Intervention
Current Drug Targets Recent US Patents on Extracellular Matrix in Tissue Engineering and Regenerative Medicine
Recent Patents on Regenerative Medicine Implication of Heat Shock Protein 90 (HSP90) in Tumor Angiogenesis: A Molecular Target for Anti-Angiogenic Therapy?
Current Cancer Drug Targets Zinc Dependent Histone Deacetylase Inhibitors in Cancer Therapeutics: Recent Update
Current Medicinal Chemistry Trabectedin (Yondelis®) as a Therapeutic Option in Gynecological Cancers: A Focus on its Mechanisms of Action, Clinical Activity and Genomic Predictors of Drug Response
Current Drug Targets The Chlorophyll Catabolite Pheophorbide a as a Photosensitizer for the Photodynamic Therapy
Current Medicinal Chemistry Applications of Nanosystems to Anticancer Drug Therapy (Part II. Dendrimers, Micelles, Lipid-based Nanosystems)
Recent Patents on Anti-Cancer Drug Discovery Measurement of CYP1A2 Activity: A Focus on Caffeine as a Probe
Current Drug Metabolism Interrelationships Among Gut Microbiota and Host: Paradigms, Role in Neurodegenerative Diseases and Future Prospects
CNS & Neurological Disorders - Drug Targets Effects of Edible Algae Polysaccharides on Allergic, Inflammatory, and Anti-Tumor Responses Through Toll-Like Receptor 4
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry A Novel Marine Drug, SZ–685C, Induces Apoptosis of MMQ Pituitary Tumor Cells by Downregulating miR–200c
Current Medicinal Chemistry Bladder Injury During Cesarean Delivery
Current Women`s Health Reviews