Ubiquitination Governing DNA Repair


Book Description

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.




Proteolytic Signaling in Health and Disease


Book Description

In recent years, powered by evolving technologies and experimental design, studies have better illuminated the regulating role of proteolytic enzymes across human development and pathologies. Proteolytic Signaling in Health and Disease provides an in-depth discussion of fundamental physiological and developmental processes regulated by proteases, from protein turnover and autophagy to antigen processing and presentation and major histocompatibility complex (MHC) molecules. Moving on from basic biology, international chapter authors examine a range of pathological conditions associated with proteolysis, including inflammation, wound healing, and cancer. Later chapters discuss the newly discovered network of connected events among proteases (and their inhibitors), the so-called ‘protease web’, and how best to study it. This book also empowers new research with up-to-date analytical methods and step-by-step protocols for studying proteolytic signaling events. Examines biological events triggered by proteolytic enzyme activity across human development and pathologies Discusses the role of proteolytic signaling in inflammation, wound healing, and cancer, among other disease types Features methods and protocols supporting further study of proteolytic signaling events Includes chapter contributions from international leaders in the field




Ubiquitin Proteasome System


Book Description

The human ubiquitin proteasome system (UPS) is comprised of nearly 1000 proteins. Although originally identified as a mechanism of protein destruction, the UPS has numerous additional functions and mediates central signaling events in myriad processes involved in both cellular and organismal health and homeostasis. Numerous pathways within the UPS are implicated in disease, ranging from cancer to neurodegenerative diseases such as Parkinson's. The goal of this book is to deliver a collection of synopses of current areas of UPS research that highlights the importance of understanding the biology of the UPS to identify disease-relevant pathways, and the need to elucidate the molecular machinations within the UPS to develop methods for therapeutic modulation of these pathways.




The Ubiquitin Proteasome System


Book Description

“This volume explores numerous techniques used to study the ubiquitin proteasome system. The chapters in this book are organized into five parts and cover topics such as determining the mechanisms of action for E2s, E3s, and DUB enzymes; the latest advances to study the formation of poly-ubiquitin chains as well as their linkage types; the binding partners of proteins in the UPS; methods for structure determination by x-ray crystallography, cryo electron microscopy and SAXS; screening assays to select for degrons or modulators of E3s and DUBs; proteomics approaches in the ubiquitin field and methods to study 26S proteasome function. Written in the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Thorough and authoritative, The Ubiquitin Proteasome System: Methods and Protocols is a valuable resource for both experienced and novice scientists who are interested in expanding their knowledge in this field.




SUMO Regulation of Cellular Processes


Book Description

This is the second edition of a very well received book that details how the sumoylation system functions and how it modulates numerous cellular activities. SUMO is a post-translational modifier in the ubiquitin super-family that has gained recognition over the last twenty years as an essential and prevalent regulatory molecule. Individual chapters explore the biochemistry, molecular biology, and cell biology of the sumoylation system and its substrate proteins. The book is divided into three themed parts: Molecular Functions (I), Cell Growth Regulation (II), and Diseases (III). Parts I and II focus on the contribution of sumoylation to cellular activities in both the nuclear and cytoplasmic compartments. The nuclear activities covered include nucleic acid metabolism (both RNA and DNA), chromosome structure and replication, and nucleocytoplasmic transport. Cytoplasmic processes presented include regulation of membrane ion channels, general metabolism, and apoptotic signalling. Topics in Part III include the role of sumoylation in developmental abnormalities (craniofacial and cardiovascular), diabetes, neurodegenerative diseases, cancer, and infections with viruses and bacteria. Each of the corresponding chapter authors is an active researcher who has made significant contributions to understanding sumoylation. This second edition provides updates and revisions to most of the original chapters plus adds six new chapters to address important developing areas of sumoylation research. This volume is intended for a scientific audience from undergraduates to independent researchers. The content will serve as both a solid introduction for the novice reader and an in depth treatment for the advanced scholar.




Ubiquitination Governing DNA Repair - Implications in Health and Disease


Book Description

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.




Environmental Epigenetics


Book Description

This book examines the toxicological and health implications of environmental epigenetics and provides knowledge through an interdisciplinary approach. Included in this volume are chapters outlining various environmental risk factors such as phthalates and dietary components, life states such as pregnancy and ageing, hormonal and metabolic considerations and specific disease risks such as cancer cardiovascular diseases and other non-communicable diseases. Environmental Epigenetics imparts integrative knowledge of the science of epigenetics and the issues raised in environmental epidemiology. This book is intended to serve both as a reference compendium on environmental epigenetics for scientists in academia, industry and laboratories and as a textbook for graduate level environmental health courses. Environmental Epigenetics imparts integrative knowledge of the science of epigenetics and the issues raised in environmental epidemiology. This book is intended to serve both as a reference compendium on environmental epigenetics for scientists in academia, industry and laboratories and as a textbook for graduate level environmental health courses.







How Tobacco Smoke Causes Disease


Book Description

This report considers the biological and behavioral mechanisms that may underlie the pathogenicity of tobacco smoke. Many Surgeon General's reports have considered research findings on mechanisms in assessing the biological plausibility of associations observed in epidemiologic studies. Mechanisms of disease are important because they may provide plausibility, which is one of the guideline criteria for assessing evidence on causation. This report specifically reviews the evidence on the potential mechanisms by which smoking causes diseases and considers whether a mechanism is likely to be operative in the production of human disease by tobacco smoke. This evidence is relevant to understanding how smoking causes disease, to identifying those who may be particularly susceptible, and to assessing the potential risks of tobacco products.




Proteostasis and Disease


Book Description

This book, written by members of the European network PROTEOSTASIS, provides an up-to-date review of the research regarding protein homeostasis in health and disease. With new discoveries contributing to the increasing complexity of this topic, the book offers a detailed overview of the pathways regulating protein homeostasis, including autophagy and the ubiquitin protein family. Following a basic introduction, it explains how defects in protein homeostasis contribute to numerous pathologies, including cancer, neurodegeneration, inflammation and a number of rare diseases. In addition, it discusses, the role of protein homeostasis in cellular development and physiology. Highlighting the latest research in the field of protein homeostasis and its implications for various clinically relevant diseases, the book appeals to researchers and clinicians, while also offering a reference guide for scholars who are new to the field.