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DNA Repair and Human Disease highlights the molecular complexities of a few well-known human hereditary disorders that arise due to perturbations in the fidelity of diverse DNA repair machineries.
Cutting edge reviews by leading researchers illuminate key aspects of DNA repair in mammalian systems and its relationship to human genetic disease and cancer. Major topics include UV and X-Ray repair, repair of chemical damage, recombinational repair, mismatch repair, transcription-repair coupling, and the role of DNA repair in disease prevention. Extensive up-to-date references and rigorous peer-review of each chapter make this volume definitive and bring it to the active frontiers of research.
The overall aim of this book is to give scientists in academia and industry a comprehensive overview of the field of DNA damage and DNA repair and related human diseases.
The DNA of all organisms is constantly being damaged by endogenous and exogenous sources. Oxygen metabolism generates reactive species that can damage DNA, proteins and other organic compounds in living cells. Exogenous sources include ionizing and ultraviolet radiations, carcinogenic compounds and environmental toxins among others. The discovery of multiple DNA lesions and DNA repair mechanisms showed the involvement of DNA damage and DNA repair in the pathogenesis of many human diseases, most notably cancer. These books provide a comprehensive overview of the interdisciplinary area of DNA damage and DNA repair, and their relevance to disease pathology. Edited by recognised leaders in the field, this two-volume set is an appealing resource to a variety of readers including chemists, chemical biologists, geneticists, cancer researchers and drug discovery scientists.
DNA Repair and Human Disease highlights the molecular complexities of a few well-known human hereditary disorders that arise due to perturbations in the fidelity of diverse DNA repair machineries.
Physical and chemical agents in the environment damage the DNA of humans, and pose a major threat to human health today, and to the genetic integrity of human populations. Although studies on isolated DNA in vitro, on prokaryotes, on mammalian cells in culture, and on laboratory animals have provided essential background information, it is now possible to study DNA damage and repair in human tissues directly. New techniques of high sensitivity, especially those not requiring radioactive labeling have made possible quantitation of DNA damage and repair, as well as detection of residual, unrepaired DNA lesions . In recent years, several investigators have taken up the challenge of studying damage and repair responses in humans, and we have chosen that work as the special focus of this Symposium. Major advances in under standing damage and responses in human skin, in blood cells and in human internal organs indicate three major themes. First, DNA damage levels in human tissues depend not only on the initial exposures, but also on the capapacity of that tissue for repair of the specific lesion type. Second, repair in human tissues may differ quantitatively and qualitatively from that in human cells in culture.
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 damage response (DDR) and lesion repair are vital processes ensuring genome integrity through various pathways depending mainly on the nature of DNA injury and cell cycle stage. DDR is finely regulated at many levels in co-ordination with other ongoing processes as is genome replication and cell cycle progression. Posttranslational modifications (PTMs), affecting both protein-protein and protein-DNA interactions, play a crucial role in finely tuning all processes involved in the restoration of genome lesions. Regarding damaged chromatin, PTMs serve in many cases as recruitment platforms for DNA repair mechanisms by facilitating binding sites or regulating interactions between involved proteins. Ubiquitination, the addition of ubiquitin moieties on a target protein, apart from controlling protein availability through degradation, is also involved, together with partner small ubiquitin-like modifier (SUMO), in controlling many pathways involved in DDR by modifying the structure-function relationship and thus interacting with partner molecules. The aim of this book is to cover a broad spectrum of current topics in ubiquitination and to a lesser extent SUMOylation involvement in regulation of DDR and repair in health and disease. This book is intended for pre- and postgraduate students and young scientists in this field. Members of both academic and research institutions, actively involved in the field, have described their current understanding of major mechanisms involved, highlighted key events, described ongoing applications in both developmental diseases and cancer and provided hints for future potential applications.