An essential resource for all scientists researching cellular responses to DNA damage. • Introduces important new material reflective of the major changes and developments that have occurred in the field over the last decade. • Discussed the field within a strong historical framework, and all aspects of biological responses to DNA damage are detailed. • Provides information on covering sources and consequences of DNA damage; correcting altered bases in DNA: DNA repair; DNA damage tolerance and mutagenesis; regulatory responses to DNA damage in eukaryotes; and disease states associated with defective biological responses to DNA damage.
DNA Repair and Cancer Therapy: Molecular Targets and Clinical Applications, Second Edition provides a comprehensive and timely reference that focuses on the translational and clinical use of DNA repair as a target area for the development of diagnostic biomarkers and the enhancement of cancer treatment. Experts on DNA repair proteins from all areas of cancer biology research take readers from bench research to new therapeutic approaches. This book provides a detailed discussion of combination therapies, in other words, how the inhibition of repair pathways can be coupled with chemotherapy, radiation, or DNA damaging drugs. Newer areas in this edition include the role of DNA repair in chemotherapy induced peripheral neuropathy, radiation DNA damage, Fanconi anemia cross-link repair, translesion DNA polymerases, BRCA1-BRCA2 pathway for HR and synthetic lethality, and mechanisms of resistance to clinical PARP inhibitors. - Provides a comprehensive overview of the basic and translational research in DNA repair as a cancer therapeutic target - Includes timely updates from the earlier edition, including Fanconi Anemia cross-link repair, translesion DNA polymerases, chemotherapy induced peripheral neuropathy, and many other new areas within DNA repair and cancer therapy - Saves academic, medical, and pharma researchers time by allowing them to quickly access the very latest details on DNA repair and cancer therapy - Assists researchers and research clinicians in understanding the importance of the breakthroughs that are contributing to advances in disease-specific research
Within the past two decades, extraordinary new functions for the nucleolus have begun to appear, giving the field a new vitality and generating renewed excitement and interest. These new discoveries include both newly-discovered functions and aspects of its conventional role. The Nucleolus is divided into three parts: nucleolar structure and organization, the role of the nucleolus in ribosome biogenesis, and novel functions of the nucleolus.
The free-radical chemistry of DNA had been discussed in some detail in 1987 in my book The Chemical Basis of Radiation Biology. Obviously, the more recent developments and the concomitant higher level of understanding of mechanistic details are missing. Moreover, in the living cell, free-radical DNA damage is not only induced by ionizing radiation, but free-radical-induced DNA damage is a much more general phenomenon. It was, therefore, felt that it is now timely to review our present knowledge of free-radical-induced DNA damage induced by all conceivable free-radical-generating sources. Originally, it had been thought to include also a very important aspect, the repair of DNA damage by the cell’s various repair enzymes. Kevin Prise (Cancer Campaign, Gray Laboratory, L- don) was so kind to agree to write this part. However, an adequate description of this strongly expanding area would have exceeded the allocated space by much, and this section had to be omitted. The directors of the Max-Planck-Institut für Strahlenchemie (now MPI für Bioanorganische Chemie), Karl Wieghardt and Wolfgang Lubitz, kindly allowed me to continue to use its facilities after my retirement in 2001. Notably, our - brarian, Mrs. Jutta Theurich, and her right-hand help, Mrs. Rosemarie Schr- er, were most helpful in getting hold of the literature. I thank them very much. Without their constant help, this would have been very difficult indeed.
Environmental stresses and metabolic by-products can severely affect the integrity of genetic information by inducing DNA damage and impairing genome stability. As a consequence, plant growth and productivity are irreversibly compromised. To overcome genotoxic injury, plants have evolved complex strategies relying on a highly efficient repair machinery that responds to sophisticated damage perception/signaling networks. The DNA damage signaling network contains several key components: DNA damage sensors, signal transducers, mediators, and effectors. Most of these components are common to other eukaryotes but some features are unique to the plant kingdom. ATM and ATR are well-conserved members of PIKK family, which amplify and transduce signals to downstream effectors. ATM primarily responds to DNA double strand breaks while ATR responds to various forms of DNA damage. The signals from the activated transducer kinases are transmitted to the downstream cell-cycle regulators, such as CHK1, CHK2, and p53 in many eukaryotes. However, plants have no homologue of CHK1, CHK2 nor p53. The finding of Arabidopsis transcription factor SOG1 that seems functionally but not structurally similar to p53 suggests that plants have developed unique cell cycle regulation mechanism. The double strand break repair, recombination repair, postreplication repair, and lesion bypass, have been investigated in several plants. The DNA double strand break, a most critical damage for organisms are repaired non-homologous end joining (NHEJ) or homologous recombination (HR) pathway. Damage on template DNA makes replication stall, which is processed by translesion synthesis (TLS) or error-free postreplication repair (PPR) pathway. Deletion of the error-prone TLS polymerase reduces mutation frequencies, suggesting PPR maintains the stalled replication fork when TLS is not available. Unveiling the regulation networks among these multiple pathways would be the next challenge to be completed. Some intriguing issues have been disclosed such as the cross-talk between DNA repair, senescence and pathogen response and the involvement of non-coding RNAs in global genome stability. Several studies have highlighted the essential contribution of chromatin remodeling in DNA repair DNA damage sensing, signaling and repair have been investigated in relation to environmental stresses, seed quality issues, mutation breeding in both model and crop plants and all these studies strengthen the idea that components of the plant response to genotoxic stress might represent tools to improve stress tolerance and field performance. This focus issue gives researchers the opportunity to gather and interact by providing Mini-Reviews, Commentaries, Opinions, Original Research and Method articles which describe the most recent advances and future perspectives in the field of DNA damage sensing, signaling and repair in plants. A comprehensive overview of the current progresses dealing with the genotoxic stress response in plants will be provided looking at cellular and molecular level with multidisciplinary approaches. This will hopefully bring together valuable information for both plant biotechnologists and breeders.
This book is intended for students and scientists working in the field of DNA repair, focusing on a number of topics ranging from DNA damaging agents and mechanistic insights to methods in DNA repair and insights into therapeutic strategies. These topics demonstrate how scientific ideas are developed, tested, dialogued, and matured as it is meant to discuss key concepts in DNA repair. The book should serve as a supplementary text in courses and seminars as well as a general reference for biologists with an interest in DNA repair.
In recent years, a number of groundbreaking structural and mechanistic studies deepened our understanding of helicase mechanisms and established new approaches for their analyses. Many fundamental mechanistic questions ranging from the mechanism of force generation, mechanochemical coupling to distinct mechanisms by which the same enzyme translocates on DNA removing obstacles, unwinds DNA and/or remodels nucleoprotein complexes, however, remain to be answered. It is even less understood how the helicase motors are incorporated into a wide range of genome maintenance and repair machines. The field has reached a stage when the studies of molecular mechanisms and basic biology of helicases can and shall be integrated with the studies of development, cancer and longevity. The objective of this book is to provide the first systematic overview of structure, function and regulation of DNA helicases and related molecular motors. By integrating the knowledge obtained through the diverse technical approaches ranging from single-molecule biophysics to cellular and molecular biological studies the editors aim to provide a unified view on how helicases function in the cell, are regulated in response to different cellular stresses and are integrated into large macromolecular assemblies to form a complex and adaptive living system.
In recent years the field of DNA repair has flourished due to new findings on DNA repair mechanisms and the molecular basis of cancer. This volume covers the most recent developments in this research field and contains contributions from scientists working in various fields.
