Download or read book Ubiquitin like Proteins and the DNA Damage Response written by Jessica Suzanne Brown and published by . This book was released on 2015 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Ubiquitination Governing DNA Repair written by Effrossyni Boutou and published by BoD – Books on Demand. This book was released on 2018-08-01 with total page 221 pages. Available in PDF, EPUB and Kindle. Book excerpt: 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.

Download or read book Ubiquitin and Ubiquitin Relative SUMO in DNA Damage Response written by Kristijan Ramadan and published by Frontiers Media SA. This book was released on 2018-02-09 with total page 183 pages. Available in PDF, EPUB and Kindle. Book excerpt: DNA damage response (DDR) is a term that includes a variety of highly sophisticated mechanisms that cells have evolved in safeguarding the genome from the deleterious consequences of DNA damage. It is estimated that every single cell receives tens of thousands of DNA lesions per day. Failure of DDR to properly respond to DNA damage leads to stem cell dysfunction, accelerated ageing, various degenerative diseases or cancer. The sole function of DDR is to recognize diverse DNA lesions, signal their presence, activate cell cycle arrest and finally recruit specific DNA repair proteins to fix the DNA damage and thus prevent genomic instability. DDR is composed of hundreds of spatiotemporally regulated and interconnected proteins, which are able to promptly respond to various DNA lesions. So it is not surprising that mutations in genes encoding various DDR proteins cause embryonic lethality, malignancies, neurodegenerative diseases and premature ageing. The importance of DDR for cell survival and genome stability is unquestionable, but how the sophisticated network of hundreds of different DDR proteins is spatiotemporally coordinated is far from being understood. In the last ten years ubiquitin (ubiquitination) and the ubiquitin-relative SUMO (sumoylation) have emerged as essential posttranslational modifications that regulate DDR. Beside a plethora of ubiqutin and sumo E1-activating enzymes, E2-conjugating enzymes, E3-ligases and ubiquitin/sumo proteases involved in ubiquitination and sumoylation, the complexity of ubiqutin and sumo systems is additionally increased by the fact that both ubiquitin and sumo can form a variety of different chains on substrates which govern the substrate fate, such as its interaction with other proteins, changing its enzymatic activity or promoting substrate degradation. The importance of ubiquitin/SUMO systems in the orchestration of DDR is best illustrated in patients with mutations in E3-ubiquitin ligases BRCA1 or RNF168. BRCA1 is essential for proper function of DDR and its mutations lead to triple-negative breast and ovarian cancers. RNF168 is an E3 ubiquitin ligase, which creates the ubiquitin docking platform for recruitment of different DNA damage signalling and repair proteins at sites of DNA lesion, and its mutations cause RIDDLE syndrome characterized by radiosensitivity, immunodeficiency and learning disability. In addition, recently discovered the ubiquitin receptor protein SPRTN is part of the DNA replication machinery and its mutations cause early-onset hepatocellular carcinoma and premature ageing in humans. Despite more than 700 different enzymes directly involved in ubiquitination and sumoylation processes only few of them are known to play a role in DDR. Therefore, we feel that the role of ubiquitin and the ubiquitin-related SUMO in DDR is far from being understood, and that this is the emerging field that will hugely expand in the next decade due to the rapid development of a new generation of technologies, which will allow us a more robust and precise analyses of human genome, transcriptome and proteome. In this Research Topic we provide a comprehensive overview of our current understanding of ubiquitin and SUMO pathways in all aspects of DDR, from DNA replication to different DNA repair pathways, and demonstrate how alterations in these pathways cause genomic instability that is linked to degenerative diseases, cancer and pathological ageing.

Download or read book Ubiquitination Governing DNA Repair Implications in Health and Disease written by Horst-Werner Stürzbecher and published by . This book was released on 2018 with total page 220 pages. Available in PDF, EPUB and Kindle. Book excerpt: 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.

Download or read book Ubiquitin Family Proteins in DNA Damage Response written by and published by . This book was released on 2011 with total page 160 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Ubiquitin and Ubiquitin Relative SUMO in DNA Damage Response written by and published by . This book was released on 2018 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: DNA damage response (DDR) is a term that includes a variety of highly sophisticated mechanisms that cells have evolved in safeguarding the genome from the deleterious consequences of DNA damage. It is estimated that every single cell receives tens of thousands of DNA lesions per day. Failure of DDR to properly respond to DNA damage leads to stem cell dysfunction, accelerated ageing, various degenerative diseases or cancer. The sole function of DDR is to recognize diverse DNA lesions, signal their presence, activate cell cycle arrest and finally recruit specific DNA repair proteins to fix the DNA damage and thus prevent genomic instability. DDR is composed of hundreds of spatiotemporally regulated and interconnected proteins, which are able to promptly respond to various DNA lesions. So it is not surprising that mutations in genes encoding various DDR proteins cause embryonic lethality, malignancies, neurodegenerative diseases and premature ageing. The importance of DDR for cell survival and genome stability is unquestionable, but how the sophisticated network of hundreds of different DDR proteins is spatiotemporally coordinated is far from being understood. In the last ten years ubiquitin (ubiquitination) and the ubiquitin-relative SUMO (sumoylation) have emerged as essential posttranslational modifications that regulate DDR. Beside a plethora of ubiqutin and sumo E1-activating enzymes, E2-conjugating enzymes, E3-ligases and ubiquitin/sumo proteases involved in ubiquitination and sumoylation, the complexity of ubiqutin and sumo systems is additionally increased by the fact that both ubiquitin and sumo can form a variety of different chains on substrates which govern the substrate fate, such as its interaction with other proteins, changing its enzymatic activity or promoting substrate degradation. The importance of ubiquitin/SUMO systems in the orchestration of DDR is best illustrated in patients with mutations in E3-ubiquitin ligases BRCA1 or RNF168. BRCA1 is essential for proper function of DDR and its mutations lead to triple-negative breast and ovarian cancers. RNF168 is an E3 ubiquitin ligase, which creates the ubiquitin docking platform for recruitment of different DNA damage signalling and repair proteins at sites of DNA lesion, and its mutations cause RIDDLE syndrome characterized by radiosensitivity, immunodeficiency and learning disability. In addition, recently discovered the ubiquitin receptor protein SPRTN is part of the DNA replication machinery and its mutations cause early-onset hepatocellular carcinoma and premature ageing in humans. Despite more than 700 different enzymes directly involved in ubiquitination and sumoylation processes only few of them are known to play a role in DDR. Therefore, we feel that the role of ubiquitin and the ubiquitin-related SUMO in DDR is far from being understood, and that this is the emerging field that will hugely expand in the next decade due to the rapid development of a new generation of technologies, which will allow us a more robust and precise analyses of human genome, transcriptome and proteome. In this Research Topic we provide a comprehensive overview of our current understanding of ubiquitin and SUMO pathways in all aspects of DDR, from DNA replication to different DNA repair pathways, and demonstrate how alterations in these pathways cause genomic instability that is linked to degenerative diseases, cancer and pathological ageing.

Download or read book Fundamentals of Chromatin written by Jerry L. Workman and published by Springer Science & Business Media. This book was released on 2013-12-04 with total page 594 pages. Available in PDF, EPUB and Kindle. Book excerpt: ​​​​​​​​​​​​​While there has been an increasing number of books on various aspects of epigenetics, there has been a gap over the years in books that provide a comprehensive understanding of the fundamentals of chromatin. ​Chromatin is the combination of DNA and proteins that make up the genetic material of chromosomes. Its primary function is to package DNA to fit into the cell, to strengthen the DNA to prevent damage, to allow mitosis and meiosis, and to control the expression of genes and DNA replication. The audience for this book is mainly newly established scientists ​and graduate students. Rather than going into the more specific areas of recent research on chromatin the chapters in this book give a strong, updated groundwork about the topic. Some the fundamentals that this book will cover include the structure of chromatin and biochemistry and the enzyme complexes that manage it.

Download or read book SUMOylation and Ubiquitination written by Van G. Wilson and published by . This book was released on 2019-09 with total page 512 pages. Available in PDF, EPUB and Kindle. Book excerpt: Most proteins undergo post-translational modifications altering physical and chemical properties, folding, conformation distribution, stability, activity and function. Ubiquitin and SUMOs are related small proteins that are members of the large ubiquitin superfamily of post-translational modifiers. Written by highly respected leaders in their fields under the expert guidance of the editor, this volume covers the principles of ubiquitination and SUMOylation, presents detailed reviews of current and emerging concepts and highlights new advances in all areas of SUMOylation and ubiquitination. Topics of note include: the ubiquitin superfamily, the ubiquitin toolbox, onco viral exploitation of the SUMO system, small molecule modulators of desumoylation, mass spectrometry, global proteomic profiling of SUMO and ubiquitin, biotin-based approaches, genetic screening, SUMOylation networks in humans, targets for ubiquitin ligases, regulation of p53, protein homeostasis, miRNAs, DNA replication, DNA damage response, telomere biology, intracellular trafficking, regulation of angiogenesis, brain ischemia, autophagy, assembly and activity, antiviral defense, HIV infection, amyloid and amyloid-like proteins, plant immunity. This comprehensive and up-to-date book is the definitive reference volume on all aspects of SUMOylation and ubiquitination and is an essential acquisition for anyone involved in this area of biology.

Download or read book The Ubiquitin Proteasome System written by Thibault Mayor and published by Humana. This book was released on 2019-10-06 with total page 413 pages. Available in PDF, EPUB and Kindle. Book excerpt: “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.

Download or read book Ubiquitination in the UV induced DNA Damage Response from Proteomics to Patient written by and published by . This book was released on 2014 with total page 140 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Analyzing Ubiquitin Signaling in Protein Homeostasis and DNA Damage Response written by Jan Bernhard Heidelberger and published by . This book was released on 2020 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Ubiquitin Proteasome System written by Matthew Summers and published by BoD – Books on Demand. This book was released on 2019-06-19 with total page 228 pages. Available in PDF, EPUB and Kindle. Book excerpt: 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.

Download or read book Protein Ubiquitination in IR Induced DNA Damage Response written by Nur Yucer and published by . This book was released on 2012 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Developing Chemical Methods to Generate Ubiquitinated Proteins and Investigating the Role of Reversible PCNA Ubiquitination in DNA Damage Response written by Kun Yang and published by . This book was released on 2022 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Ubiquitination of proteins regulates a variety of cellular processes, including protein degradation, NF-ÎðB pathway activation, apoptosis and DNA damage tolerance. Methods for generating ubiquitinated proteins are needed for an in-depth molecular understanding of protein ubiquitination. For my graduate research, I developed a cysteine-based ligation strategy to generate monoubiquitinated proliferating cell nuclear antigen (PCNA) protein while preserving the native cysteines on PCNA. The chemically ubiquitinated PCNA retains normal function as the native Ub-PCNA in stimulating the ATPase activity of replication factor C (RFC) and lesion bypass synthesis by PolÎʺ. This method may be adapted for chemical ubiquitination of other proteins and for site specific modification of a target protein at a specific site through sulfhydryl chemistry. Besides monoubiquitination of proteins, a new chemical approach for protein polyubiquitination was developed with a defined ubiquitin chain length and linkage under a mild condition. Using the chemically polyubiquitinated PCNA, I revealed a mechanism of the K63 polyubiquitin chain on PCNA in promoting the error-free lesion bypass by suppressing the DNA translesion synthesis (TLS). In addition, I demonstrated in a reconstituted system that deubiquitination of PCNA by Ubp10 promoted the reverse polymerase switching between PolÎʺ and PolÎþ, which could promote restoration of the normal DNA replication by PolÎþ after lesion bypass synthesis by PolÎʺ.

Download or read book The Ubiquitin System written by Milton J. Schlesinger and published by Cold Spring Harbor Laboratory Press. This book was released on 1988 with total page 218 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book DNA Damage Recognition written by Wolfram Siede and published by CRC Press. This book was released on 2005-09-19 with total page 871 pages. Available in PDF, EPUB and Kindle. Book excerpt: Stands as the most comprehensive guide to the subject-covering every essential topic related to DNA damage identification and repair. Covering a wide array of topics from bacteria to human cells, this book summarizes recent developments in DNA damage repair and recognition while providing timely reviews on the molecular mechanisms employe

Download or read book Regulation of Ubiquitylation and Ubiquitin like Post Translational Modifications written by Ryan Lumpkin and published by . This book was released on 2019 with total page 155 pages. Available in PDF, EPUB and Kindle. Book excerpt: Ubiquitin (Ub) is an 8,500 Da, 76 amino acid protein that is among a family of similar Ubiquitin-like proteins. E3 Ligases facilitate the attachment of Ub onto lysine residues of substrate proteins. Ub can also be attached to another Ub molecule, forming polyubiquitin chains which signal for proteasomal degradation and the immune response. Small ubiquitin-like modifier (SUMO) is involved in cell cycle control and the DNA damage response. Another Ubiquitin-like protein, Neural precursor cell expressed developmentally down-regulated protein 8 (NEDD8), can modify some E3 Ligases to regulate their activation. Chapter II presents a novel method for the side-by-side identification and quantification of Ubiquitin and SUMO modifications. Trypsin digestion of a Ubiquitin-modified protein leaves a diglycyl-lysine at the site of modification, which can be detected by mass spectrometry. Unlike Ubiquitin, detection of SUMOylated proteins is limited by the lack of naturally occurring protease sites in the C-terminal tail of SUMO proteins. This chapter describes detection of endogenous SUMOylation using [alpha]-lytic protease, WaLP. Hydrogen-deuterium exchange mass spectrometry (HDX-MS) probes the solvent accessibility and conformational dynamics of proteins by measuring deuterium uptake on backbone amides over time. Chapter III describes an open-source software package designed to automate the correction, analysis and visualization of HDX-MS data. Chapter IV investigates the structure, dynamics and regulation of an ASB9-CUL-RING E3 Ubiquitin Ligase. The structure of the substrate-receptor complex was determined for the first time by Cryo-EM, identifying changes in both the receptor and the substrate that were not predicted by previous models. Chapter V further investigates the dynamics, regulation and activity of the ASB9-CUL-RING E3 Ubiquitin Ligase. In vitro assays, western blots and mass spectrometry data describe the locations and intensity of ubiquitin modifications. These data show that ARIH2, another E3 ligase, is necessary for initial substrate modification, and that the addition of other E2 enzymes can modulate the poly-ubiquitin chains formed. HDX-MS studies show that modification of the ASB9-CUL-RING ligase causes conformational restructuring that facilitates the binding and activation of ARIH2.