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This book provides up-to-date coverage of selected topics in nucleic acid oxidation. The topics have been selected to cover everything from basic chemical mechanisms, repair of damage and the biological and pathological meaning of DNA oxidation. The chapters are authored by leading, research active, international experts in the respective topics.
Summary: Increased levels of reactive oxygen species (ROS) are present in almost all cancers. Since increased levels of ROS can cause serious damage to nucleic acids, carbohydrates, lipids and proteins, understanding how cancer cells sustain their altered biology could identify ways to selectively target transformed cells. ... Here, we identify an expanded role for PA28y in the cellular response to oxidative stress. ... Taken together, our data reveal an expanded role for PA28y in the cellular response to oxidative damage, perhaps playing an important role in the recognition of oxidatively-damaged DNA. -- Abstract.
DNA stores and passes the genetic information of almost all living organisms. Its molecular structure and their intramolecular interactions are particularly suitable to maximize stability against oxidative stress and UV-light absorption. Yet the protection and repair strategies are still error-prone: DNA lesions are produced, including the most complex and highly mutagenic ones. An important threat to DNA stability comes from photosensitization, i.e. from the dramatic multiplication of radiation-induced defects mediated by the presence of organic or organometallic dyes compared to the direct exposure to UVA radiation. Moreover, the photo-induced production of singlet oxygen generates an extremely high oxidative stress on DNA that, in vivo, normally results in extended cellular apoptosis. Elucidating the processes leading to DNA damages, from the production of a simple radical entity to deleterious lesions, as well as the opportunities of repair by devoted enzymes, is a cornerstone towards the development of more efficient protection strategies. Sensitization and selective production of DNA lesions can also be exploited to induce the selective apoptosis of cancer cells upon exposition to radiation or to oxidative stress, for instance in the field of photodynamic therapy. The importance and relevance of the field is witnessed by the impressive amount of high-level papers dealing with this complex subject, and notably tackling the structural elucidation of DNA and DNA-drug adducts, the mechanisms of formation of DNA lesions (including the precise detection of the final lesion products), as well as the influence of the lesions on the DNA stability and dynamics and the consequences on the ease of repair. Due to the complexity of the field lying at the frontiers between chemistry, physics and biology, multidisciplinary strategies allying modeling and experience are needed. This topic aims at giving an extended overview of the current research in the domain, with fundamental contribution from the leading groups in the field of DNA reactivity, structural characterization, photo-chemistry and photo-physics, as well as repair mechanism. It will therefore be a fundamental guide for scientists wanting to address the field of DNA lesion and repair, but also more generally for researchers working in rational drug design or in the development of biomarkers and medical imaging techniques
Ribonucleic acid (RNA) is a macromolecule that plays a central role in cell physiology: RNA molecules act as intermediates between the deoxyribonucleic acid (DNA), where genetic information is stored, and proteins, which perform the necessary functions within the cell. Traditionally, the structural and functional properties of RNA are closely linked to gene expression. However, RNA-based enzymes, called ribozymes, are also involved in catalysis and small RNAs regulate key cellular processes, such as cell growth, division, differentiation, aging and death. RNA is a sensitive macromolecule that can be easily damaged by environmental conditions (ultraviolet radiation, oxidative stress) and biological factors (ribonucleases, ribotoxins, CRISPR-Cas systems). Therefore, cells have developed mechanisms to protect and/or repair RNA molecules. This book presents an overview of the biology of RNA damage, protection and repair in prokaryotes and eukaryotes. Individual chapters cover the expression regulation, enzymology and physiological role of such systems, and link them to important human diseases such as cancer and degenerative diseases.
This book was inspired by the presentations delivered at the Oxidative Damage & Repair Symposium (November, 1990). The book is organized into 20 chapters which mirror the 20 session topics of the Oxidative Damage & Repair Symposium.
This volume is comprised of 18 chapters, covering various aspects of DNA modification and RNA modified bases. It also discusses in detail circular RNA, therapeutic oligonucleotides and their different properties. The chemical nature of DNA, RNA, protein and lipids makes these macromolecules easily modifiable, but they are also susceptible to damage from both endogenous and exogenous agents. Alkylation and oxidation show a potential to disrupt the cellular redox equilibrium and cause cellular damage leading to inflammation and even chronic disease. Furthermore, DNA damage can drive mutagenesis and the resulting DNA sequence changes can induce carcinogenesis and cancer progression. Modified nucleosides can occur as a result of oxidative DNA damage and RNA turnover, and are used as markers for various diseases. To function properly some RNA needs to be chemically modified post-transcriptionally. Dysregulation of the RNA-modification pattern or of the levels of the enzymes that catalyze these modifications alters RNA functionality and can result in complex phenotypes, likely due to defects in protein translation. While modifications are best characterized in noncoding ribonucleic acids like tRNA and rRNA, coding mRNAs have also been found to contain modified nucleosides. This book is a valuable resource, not only for graduate students but also researchers in the fields of molecular medicine and molecular biology.
Environmental Damage to DNA and the Protective Effects of Phytochemicals provides information on the toxicity of natural as well as synthetic chemicals in the living systems. These can lead to DNA damage and the emergence of serious consequences or manifestations causing varied health hazards. In addition, the ten chapters of the book reflect on the possible applications of plants or plant extracts to impart protection for living cells from the xenobiotics-mediated DNA damage. The book offers comprehensive coverage of the many essential topics in the subject including: Environmental factors and DNA damage Molecular mechanisms associated with DNA damage by various environmental (Physical, Chemical and Biological) factors Synergistic effects of environmental factors Phytochemicals acting both as DNA protectants and genotoxicants Experimental models for the study of the genotoxic potential of environmental factors and protection by phytochemicals This book connects readers who possess a life sciences background to the current understanding, concept and mechanisms involved in environmental-factors-mediated DNA damage. Scientific terms are introduced, defined, described and placed appropriately in the text. The protective effect of some plant extracts/phytochemicals has also been included. Environmental Damage to DNA and the Protective Effects of Phytochemicals is intended to cater the need of BSc, MSc and research students who are striving to discover the mechanism(s) associated with protection of DNA by plant-based chemicals. This is the first edition of our book and the valuable suggestions and comments from the readers are solicited.
This book describes the methods of analysis and determination of oxidants and oxidative stress in biological systems. Reviews and protocols on select methods of analysis of ROS, RNS, oxygen, redox status, and oxidative stress in biological systems are described in detail. It is an essential resource for both novices and experts in the field of oxidant and oxidative stress biology.