Download or read book Proteomics of Poly ADP ribose Polymerases During DNA Replication and Repair written by Maria Tedim Ferreira and published by . This book was released on 2019 with total page 396 pages. Available in PDF, EPUB and Kindle. Book excerpt: In 2017, Statistics Canada reported that one out of four Canadians will die of cancer. Every day, we face environmental factors that burden our DNA with genotoxic stress. This stress can lead to severe types of DNA damage that can threaten our genomic integrity, namely double-strand breaks (DSBs). Fortunately, our cells have evolved with different repair mechanisms to deal with such lesions. There are two primary types of repair against DSBs: Homologous Recombination (HR) and Classical Non-Homologous End-Joining (CNHEJ). The HR pathway is an error-free repair mechanism used in the S-phase of the cell cycle to ensure faithful repair of the damaged area and thus preserve our genetic information. Individuals that bear mutations in proteins involved in this pathway, such as BRCA1 and BCRA2, have been associated with the development of breast and ovarian cancers. Almost 4 years ago, the field went through a major breakthrough in ovarian cancer care. A new class of drugs was accepted by the US Food and Drug Administration (FDA) to manage recurrent ovarian cancers that display HR-deficiencies. These drugs consist of inhibitor molecules against one of the earliest sensors of DNA damage in the cell: PARP-1 (poly(ADP-ribose) polymerase-1). Upon DNA damage induction, PARP-1 becomes highly activated, leading to the massive production of poly(ADP-ribose) (PAR) polymers, from the hydrolysis of nicotinamide adenine dinucleotide, which in turn modify several proteins posttranslationally and act as a scaffold to recruit DNA repair factors to the repair site. The successful application of PARP inhibitors (PARPi) arose from the observations that mutations or silencing of BRCA1/2, resulted in diminished HR activity. In the context of HR deficiency, the concomitant inhibition of PARP resulted in cell-death, an effect called synthetic lethality. Three PARPi are currently accepted by the FDA and are being clinically used for the treatment of gynaecological cancers. Notwithstanding the great promise of these inhibitors for other types of cancers, the mechanism by which these are inducing cancer lethality is not fully understood. Thus, it becomes of extreme importance to further decipher its mechanistic ways, to achieve full potential of PARPi in the clinic. To achieve this, fundamental research on the functions of PARPs and their protein partners in the DNA damage response is indispensable and constitutes the general aim of this thesis. During my doctoral work, we investigated the influence of PARP-1 during the HR pathway, primarily during the initial step of resection, which is essential for the removal of damaged DNA. Early reports of PARP-1 involvement in resection described the recruitment of the resection protein MRE11 to sites of damage in a PARP-1 dependent manner. Here, we demonstrate that PARP-1 has a novel function in DSB resection and we propose a new model for the synthetic lethality observed in HR-deficient tumors. To further complement the general aim of this doctorate, we investigated the regulatory roles of PARP-1 during the HR pathway, however in a later stage of HR resolution, at the peak formation of RAD51 foci, which is a crucial step for the efficient repair of DSBs through HR. We observed that the PAR-interactome (PARylome) at this stage was abundantly enriched with RNA-processing factors. Several of the most abundant proteins consisted of DNA and RNA helicases, as well as transcription factors, some of which were found to be mutated in tumors, and thus can be seen as potentially druggable targets to be used in combination with PARPi. We also extended our PARylome study to the chromatin proteome and investigated the histone PARylome upon DNA damage. Interestingly, we found that histone tails are not the only targets of PARP-1 and that globular domains are also targets of PARylation. Lastly, the high clinical interest of PARP-1 warrants studies addressing PARP-1 organ distribution. Thus, I finalized my studies by extensively describing and reporting PARP-1 tissular and cellular distribution and abundance in monkey organs, with the main objective of providing valuable information to any study assessing PARP inhibition efficacy and resistance in any given tissue and related diseases. In summary, this thesis provides important new information on the mechanisms PARP-1 is regulating during the response to DSBs, including the networks PARP-1 is orchestrating to potentially help reshape the cell environment, to efficiently repair the most lethal lesion our genome faces.

Download or read book Poly ADP Ribose Polymerase written by Alexei V. Tulin and published by Springer Nature. This book was released on 2022-12-14 with total page 441 pages. Available in PDF, EPUB and Kindle. Book excerpt: This detailed volume explores poly(ADP-ribose) polymerases (PARPs) in the biology of eukaryotes and their relevance to human health. Beginning with a section on the detection and quantification of poly(ADP-ribose) polymer (pADPr), the book continues by delving into the identification of protein targets, functional analysis, the poly(ADP-ribosyl)ating pathway in chromatin and genes expression, as well as the use of animal models and PARP1 inhibitor design and testing, and more. Written for the highly successful Methods in Molecular Biology series, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step and readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Authoritative and up-to-date, Poly(ADP-Ribose) Polymerase: Methods and Protocols, Third Edition presents essential new and classical methods for studying the pADPr-pathway.

Download or read book Poly ADP Ribosyl ation written by Alexander Bürkle and published by Springer Science & Business Media. This book was released on 2008-01-11 with total page 260 pages. Available in PDF, EPUB and Kindle. Book excerpt: This is the most comprehensive, up-to-date reference on this post-translational modification of proteins, which is intimately linked with DNA repair, maintenance of genomic stability, transcriptional regulation, cell death and a variety of other cellular phenomena as well as with a variety of pathophysiological conditions, including ischemia-reperfusion damage, Parkinson’s disease, Type I diabetes mellitus, hemorrhagic and septic shock and other inflammatory conditions. Richly illustrated, it offers 19 chapters written by international experts.

Download or read book Provisional Summary Record of the 18th Meeting closed Held at Headquarters New York on Friday 29 September 2000 Security Council Committee Established Pursuant to Resolution 1132 1997 Concerning Sierra Leone written by and published by . This book was released on 2000 with total page 3 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Poly ADP ribose written by Maureen I. Harris and published by . This book was released on 1974 with total page 356 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book DNA Repair in Cancer Therapy written by Mark R. Kelley and published by Academic Press. This book was released on 2016-06-07 with total page 466 pages. Available in PDF, EPUB and Kindle. Book excerpt: 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

Download or read book The Key Involvement of Poly ADP Ribosylation in Defense Against Toxic Agents in Molecular Biology Studies written by and published by . This book was released on 1991 with total page 16 pages. Available in PDF, EPUB and Kindle. Book excerpt: Poly(ADP-ribose) polymerase requires DNA for activity, and the catalytic activity of this enzyme is directly coordinated to the number of DNA strand breaks in DNA. Use of molecular techniques and the complete amino acid sequence of the enzyme, established during the past granting period, should allow us to learn considerably more about the mechanism and role of this enzyme in cells exposed to stressful environments. In AIM I. we proposed to extend our preliminary data on the insertion of full-length polymerase cDNA into various inducible and non-inducible expression vectors and retroviral vectors in both sense and antisense orientations. This would allow us to either inhibit (i.e. through antisense mRNA expression) or intensify the translation of polymerase in a variety of eukaryotic cells. A complementary approach was proposed in AIM ii where various functional domains of the polymerase as well as site-directed mutants were to be constructed into inducible expression vectors to test whether selective inhibitor's can be favorably used in cells. Once it was verified that both the engineered mRNAs and appropriate peptides were expressed in in vivo procedures in AIM HI we proposed to test for cytotoxicity and DNA repair potential and mutagenesis repair of the various reconstructed cells obtained in AIMS I AND II. poly(ADP-ribose) polymerase, Toxic agents.

Download or read book DNA Recognition and Mechanistic Investigation of Poly ADP ribose Polymerase 1 written by Meilan Wu and published by . This book was released on 2014 with total page 418 pages. Available in PDF, EPUB and Kindle. Book excerpt: Human PARP-1 is a nuclear protein containing six functional domains that catalyzes the poly(ADP-ribosyl)ation of a variety of protein substrates including itself. This process involves consumption of NAD+ as the ADP-ribose donor for forming the poly(ADP-ribose) (i.e., PAR). PARP-1 utilizes this polymerization reaction to effect its regulatory role in many important biological processes including transcription and DNA repair. Activation of PARP-1 self-modification requires the presence of damaged DNA. Activity levels of PARP-1 differ depending on the type of DNA lesion. It is proposed that the differences in activity level of PARP-1 are related to the binding stoichiometry of PARP-1 to DNA. Using double and single stranded break DNA mimics, stoichiometric analyses of PARP-1 were performed using sedimentation velocity techniques. In both cases, PARP-1 forms both 1:1 and 2:1 protein:DNA complexes, consistent with protein dimer formation. Correlation of PARP-1 activity with the DNA structure it encounters can also be explained by the utilization of different functional domains for DNA recognition. To investigate this hypothesis, DNA-binding domain AB was labeled with the Cy3 fluorophore, and a Cy5-labeled DNA with a double stranded break, was used as its interaction counterpart. Protein-DNA interactions were monitored by single molecule fluorescence colocalization. It was observed that a 2:1 protein:DNA complex is formed. Furthermore, recognition of double stranded DNA breaks by domain AB involves two different binding steps with distinct dissociation kinetics. Finally, two FRET states were observed as domain AB interacted with DNA. This suggests that domain AB utilizes different regions to interact with DNA during the recognition process. After activation, PARP-1 synthesizes poly(ADP-ribose) through three catalytic processes: initiation, elongation and branching. To study the domain requirements for polymer synthesis, truncated PARP-1 constructs ABC and DEF were tested. It was observed that initiation and elongation of short polymers requires the presence of DEF, ABC and DNA. As the polymer gets larger, DEF itself is capable of adding ADP-ribose onto the PAR polymers. Current data is consistent with a mechanistic proposal where automodification of PARP-1 happens intramolecularly and PAR elongation takes place at the distal end of the growing polymer.

Download or read book DNA Replication Recombination and Repair written by Fumio Hanaoka and published by Springer. This book was released on 2016-01-22 with total page 548 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book is a comprehensive review of the detailed molecular mechanisms of and functional crosstalk among the replication, recombination, and repair of DNA (collectively called the "3Rs") and the related processes, with special consciousness of their biological and clinical consequences. The 3Rs are fundamental molecular mechanisms for organisms to maintain and sometimes intentionally alter genetic information. DNA replication, recombination, and repair, individually, have been important subjects of molecular biology since its emergence, but we have recently become aware that the 3Rs are actually much more intimately related to one another than we used to realize. Furthermore, the 3R research fields have been growing even more interdisciplinary, with better understanding of molecular mechanisms underlying other important processes, such as chromosome structures and functions, cell cycle and checkpoints, transcriptional and epigenetic regulation, and so on. This book comprises 7 parts and 21 chapters: Part 1 (Chapters 1–3), DNA Replication; Part 2 (Chapters 4–6), DNA Recombination; Part 3 (Chapters 7–9), DNA Repair; Part 4 (Chapters 10–13), Genome Instability and Mutagenesis; Part 5 (Chapters 14–15), Chromosome Dynamics and Functions; Part 6 (Chapters 16–18), Cell Cycle and Checkpoints; Part 7 (Chapters 19–21), Interplay with Transcription and Epigenetic Regulation. This volume should attract the great interest of graduate students, postdoctoral fellows, and senior scientists in broad research fields of basic molecular biology, not only the core 3Rs, but also the various related fields (chromosome, cell cycle, transcription, epigenetics, and similar areas). Additionally, researchers in neurological sciences, developmental biology, immunology, evolutionary biology, and many other fields will find this book valuable.

Download or read book Physiology of Salt Stress in Plants written by Pratibha Singh and published by John Wiley & Sons. This book was released on 2021-09-30 with total page 272 pages. Available in PDF, EPUB and Kindle. Book excerpt: PHYSIOLOGY OF SALT STRESS IN PLANTS Discover how soil salinity affects plants and other organisms and the techniques used to remedy the issue In Physiology of Salt Stress in Plants, an editorial team of internationally renowned researchers delivers an extensive exploration of the problem of soil salinity in modern agricultural practices. It also discusses the social and environmental issues caused by salt stress. The book covers the impact of salt on soil microorganisms, crops, and other plants, and presents that information alongside examinations of salt’s effects on other organisms, including aquatic fauna, terrestrial animals, and human beings. Physiology of Salt Stress in Plants describes the morphological, anatomical, physiological, and biochemical dimensions of increasing soil salinity. It also discusses potential remedies and encourages further thought and exploration of this issue. Readers are encouraged to consider less hazardous fertilizers and pesticides, to use safer doses, and to explore and work upon salt resistant varieties of plants. Readers will also benefit from the inclusion of: Thorough introductions to salt stress perception and toxicity levels and the effects of salt stress on the physiology of crop plants at a cellular level Explorations of the effects of salt stress on the biochemistry of crop plants and salt ion transporters in crop plants at a cellular level Practical discussions of salt ion and nutrient interactions in crop plants, including prospective signalling, and the effects of salt stress on the morphology, anatomy, and gene expression of crop plants An examination of salt stress on soil chemistry and the plant-atmosphere continuum Perfect for researchers, academics, and students working and studying in the fields of agriculture, botany, entomology, biotechnology, soil science, and plant physiology, Physiology of Salt Stress in Plants will also earn a place on the bookshelves of agronomists, crop scientists, and plant biochemists.

Download or read book Ovarian Cancers written by National Academies of Sciences, Engineering, and Medicine and published by National Academies Press. This book was released on 2016-04-25 with total page 397 pages. Available in PDF, EPUB and Kindle. Book excerpt: In an era of promising advances in cancer research, there are considerable and even alarming gaps in the fundamental knowledge and understanding of ovarian cancer. Researchers now know that ovarian cancer is not a single disease-several distinct subtypes exist with different origins, risk factors, genetic mutations, biological behaviors, and prognoses. However, persistent questions have impeded progress toward improving the prevention, early detection, treatment, and management of ovarian cancers. Failure to significantly improve morbidity and mortality during the past several decades is likely due to several factors, including the lack of research being performed by specific disease subtype, lack of definitive knowledge of the cell of origin and disease progression, and incomplete understanding of genetic and non-genetic risk factors. Ovarian Cancers examines the state of the science in ovarian cancer research, identifies key gaps in the evidence base and the challenges to addressing those gaps, considers opportunities for advancing ovarian cancer research, and examines avenues for translation and dissemination of new findings and communication of new information to patients and others. This study makes recommendations for public- and private-sector efforts that could facilitate progress in reducing the incidence of morbidity and mortality from ovarian cancers.

Download or read book Click Triazoles written by Janez Košmrlj and published by Springer. This book was released on 2012-05-30 with total page 245 pages. Available in PDF, EPUB and Kindle. Book excerpt: B. R. Buckley and H. Heaney: Mechanistic Investigations of Copper(I)- Catalyzed Alkyne–Azide Cycloaddition Reactions.- J. D. Crowley and D. A. McMorran: “Click-Triazole” Coordination Chemistry: Exploiting 1,4-Disubstituted-1,2,3-Triazoles as Ligands.- S. Lee and A. H. Flood: Binding Anions in Rigid and Reconfigurable Triazole Receptors.- M. Watkinson: Click Triazoles as Chemosensors.- H.-F. Chow, C.-M. Lo and Y. Chen: Triazole-Based Polymer Gels.- T. Zheng, S. H. Rouhanifard, A. S. Jalloh, P. Wu: Click Triazoles for Bioconjugation.- S. Mignani, Y. Zhou, T. Lecourt and L. Micouin: Recent Developments in the Synthesis 1,4,5-Trisubstituted Triazoles.

Download or read book Crop Stress and its Management Perspectives and Strategies written by B. Venkateswarlu and published by Springer Science & Business Media. This book was released on 2011-11-22 with total page 617 pages. Available in PDF, EPUB and Kindle. Book excerpt: Crops experience an assortment of environmental stresses which include abiotic viz., drought, water logging, salinity, extremes of temperature, high variability in radiation, subtle but perceptible changes in atmospheric gases and biotic viz., insects, birds, other pests, weeds, pathogens (viruses and other microbes). The ability to tolerate or adapt and overwinter by effectively countering these stresses is a very multifaceted phenomenon. In addition, the inability to do so which renders the crops susceptible is again the result of various exogenous and endogenous interactions in the ecosystem. Both biotic and abiotic stresses occur at various stages of plant development and frequently more than one stress concurrently affects the crop. Stresses result in both universal and definite effects on plant growth and development. One of the imposing tasks for the crop researchers globally is to distinguish and to diminish effects of these stress factors on the performance of crop plants, especially with respect to yield and quality of harvested products. This is of special significance in view of the impending climate change, with complex consequences for economically profitable and ecologically and environmentally sound global agriculture. The challenge at the hands of the crop scientist in such a scenario is to promote a competitive and multifunctional agriculture, leading to the production of highly nourishing, healthy and secure food and animal feed as well as raw materials for a wide variety of industrial applications. In order to successfully meet this challenge researchers have to understand the various aspects of these stresses in view of the current development from molecules to ecosystems. The book will focus on broad research areas in relation to these stresses which are in the forefront in contemporary crop stress research.

Download or read book The Handbook of Neuroprotection written by Kewal K. Jain and published by Springer. This book was released on 2019-05-15 with total page 857 pages. Available in PDF, EPUB and Kindle. Book excerpt: This fully revised edition explores the management of neurological disorders with a focus on neuroprotection, disease modification, and neuroregeneration rather than symptomatic treatment. Since the publication of the first edition, advances in biotechnology, particularly in cell and gene therapies, are reflected in this volume, as are numerous new and repurposed drugs in clinical trials. Overall, The Handbook of Neuroprotection serves as a comprehensive review of neuroprotection based on knowledge of the molecular basis of disorders of the central nervous system. In-depth and authoritative, The Handbook of Neuroprotection, Second Edition features a compendium of vital knowledge aimed at providing researchers with an essential reference for this key neurological area of study.

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 ADP Ribose Transfer Reactions written by Myron K. Jacobson and published by Springer. This book was released on 2012-01-11 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Current interest in NAD (Nicotinamide adenine dinucleotide) in biological systems focuses on its role in ADP-ribose transfer reactions. These appear to be fundamentally involved in the regulation of many physiological processes. The contributions in this monograph thus represent the range of research in the very active investigation of niacin metabolism. The major topics covered are: ??? - Enzymology of ADP-Ribosylation - ADP-Ribosylation and Chromatin Function - Carcinogenesis and Differentiation - NAD Metabolism and Chemotherapy - ADP-Ribosylation and Signal Transduction - Molecular Genetic Approaches to ADP-Ribosylation

Download or read book RNA Tagging written by Manfred Heinlein and published by Humana. This book was released on 2021-08-08 with total page 490 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book provides a compendium of state-of-the-art methods for the labeling, detection, and purification of RNA and RNA-protein complexes and thereby constitutes an important toolbox for researchers interested in understanding the complex roles of RNA molecules in development, signaling, and disease. Beginning with a section on in situ detection of RNA molecules using FISH techniques, the volume continues with parts exploring in vivo imaging of RNA transport and localization, imaging and analysis of RNA uptake and transport between cells, identification and analysis of RNA-binding proteins, guide RNAs in genome editing, as well as other specific analytical techniques. Written for the highly successful Methods in Molecular Biology series, 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. Authoritative and practical, RNA Tagging: Methods and Protocols serves as a vital reference for researchers looking to further the increasingly important research in RNA biology.