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 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 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 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 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 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 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 The Proteasome Ubiquitin Protein Degradation Pathway written by Peter Zwickl and published by Springer Science & Business Media. This book was released on 2012-12-06 with total page 222 pages. Available in PDF, EPUB and Kindle. Book excerpt: This volume gives an overview of pro tea some-mediated protein degradation and the regulatory role of the ubiquitin system in cellular proteolysis. The first chapter describes the molecular evolution of the proteasome and its associated activators, i. e. , the 20S core, the base and the lid of the 19S cap, and the 11 S regulator. The ensuing chapter gives an overview of the structure and assembly of the 20S proteasome and the regulation of the archaeal proteasome by PAN. The third contribution summarizes our knowledge on the eukaryotic 26S proteasome and its regulation by the 19S regu lator, followed by a chapter devoted to the llS regulator, which elucidates the structural basis for the 11 S-mediated activation of the 20S proteasome. The fifth chapter reviews in detail the role of the proteasome in the immune response. The subsequent chapter of the natural substrates of the gives a comprehensive description proteasome and their recognition by the enzymes of the ubiqui tination machinery. The penultimate chapter rounds up the in formation on intracellular distribution of proteasomes in yeast and mammalian cells, while the last contribution highlights proteasome inhibitors, tools which proved to be very valuable for dissecting the cellular roles of the proteasome and which might turn out to be of pharmacological importance.
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 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 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 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 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 Systems Biology of Cancer written by Sam Thiagalingam and published by Cambridge University Press. This book was released on 2015-04-09 with total page 597 pages. Available in PDF, EPUB and Kindle. Book excerpt: An overview of the current systems biology-based knowledge and the experimental approaches for deciphering the biological basis of cancer.
Download or read book The Five Families of DNA Repair Proteins and Their Functionally Relevant Ubiquitination written by Niko Moses and published by . This book was released on 2018 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: The process of DNA repair, be it a response to replication dysfunction or genotoxic insult, is critical for the resolution of strand errors and the avoidance of DNA mismatches that could result in various molecular pathologies, including carcinogenic development. Here, we will describe the five main mechanisms by which DNA avoids mutation, namely the processes of base excision repair, mismatch repair, nucleotide excision repair, homologous recombination, and nonhomologous end joining. In particular, we will dissect the functional significance of various posttranslational modifications of the essential proteins within these pathways, including but not limited to ubiquitination, acetylation, and phosphorylation.
Download or read book Ubiquitin Conjugates in DNA Damage written by Laura Rachel Butler and published by . This book was released on 2011 with total page 372 pages. Available in PDF, EPUB and Kindle. Book excerpt: Each of the seven Lysine residues found in ubiquitin can participate in the isopeptide linkage between ubiquitin monomers to form polyubiquitin conjugates. While both Lysine 6 and 63 linkages are formed at DNA double-stranded breaks (DSBs), little is known about the involvement of other linkages in the DNA damage response or the dynamics of ubiquitin in DSB repair. This thesis examines the processing of DNA damage associated ubiquitin conjugates and the involvement of different types of ubiquitin linkages in DNA repair. -- POH1 (a subunit of the proteasome lid) was identified from an siRNA library screen of 103 putative human de-ubiquitinating enzymes (DUBs) as having the potential for processing DNA damage associated ubiquitin conjugates. Cells depleted for this enzyme show a normal DSB signaling cascade, with BRCAl and 53BP1 recruitment to repair foci. Further examination of POH1 revealed that it is required for processing of ubiquitin conjugates formed by DNA damage ubiquitin E3s, including BRCAl. Depletion of POH1 diminishes the ability of HeLa cells to repair DSBs by both HR and NHEJ, and induces sensitivity to DNA damaging agents. Furthermore, ChIP analysis demonstrated that the proteasome lid (and thus likely POH1) is found localised to DSBs. Together these data show that the proteasomal DUB POH1 processes ubiquitin conjugates formed during DNA damage signaling and also implicates this activity in successful completion of DSB repair. I hypothesize that POH1 acts to rescue ubiquitinated proteins at DSBs from degradation thus enabling efficient repair. -- Using expression of ubiquitin Lysine mutants, I show that a number of ubiquitin linkages are important in DNA damage repair. Of the mutants tested K6R ubiquitin expression had the greatest impact on DNA repair and survival following cisplatin treatment.
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:
