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Investigation Of The Role Of Polyadp Ribose Polymerase 1 And Par Associated Proteins In Cell Reprogramming
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Book Synopsis Investigation of the Role of Poly(ADP Ribose) Polymerase-1 and PAR Associated Proteins in Cell Reprogramming by : Bo-hua Jiang
Download or read book Investigation of the Role of Poly(ADP Ribose) Polymerase-1 and PAR Associated Proteins in Cell Reprogramming written by Bo-hua Jiang and published by . This book was released on 2015 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Book Synopsis The Role of Poly (ADP-ribose) Polymerase-1 in the Celluar Response to Several Marine-derived Compounds by : Brijesh B. Patel
Download or read book The Role of Poly (ADP-ribose) Polymerase-1 in the Celluar Response to Several Marine-derived Compounds written by Brijesh B. Patel and published by . This book was released on 2009 with total page 53 pages. Available in PDF, EPUB and Kindle. Book excerpt: PARP-1 is a multi-functional protein that is involved in many DNA-dependent genomic processes under normal and pathophysiological conditions. It is well characterized as a DNA damage detector and responds by catalytic production and attachment of polymers of ADP-ribose (PAR) to nuclear protein targets, facilitating the chromatin changes that are a prerequisite to DNA repair. In this study, we tested whether PARP-1 is involved in the cellular response to Yondelis®, Zalypsis®, PSL1, and PSL2, novel chemotherapeutic agents with putative DNA damage- and transcription-targeted activities. We observed a dose-dependent activation of PARP-1 catalytic activity following treatment with all four compounds, while PARP-1 protein levels remained unchanged. Interestingly, cells derived from PARP-1 null mice were significantly sensitized to the agents, yet, with respect to Yondelis®, only moderate DNA damage was observed which was repaired with equal efficiency by both PARP-1 wildtype and PARP-1 null cells. While the mechanism of sensitization is unclear, it is of interest to determine whether inhibition of PARP in human cells could sensitize cells to the four agents. Initial in vivo experiments testing this prediction using MX-1 breast carcinoma xenografts treated with Yondelis® alone or in combination with the PARP-1 inhibitor DIQ, demonstrate an additive effect between these two compounds with regard to tumor volume inhibition and tumor growth delay. However, corresponding in vitro experiments failed to corroborate this observation. The effects of PARP-1 on the transcription of genes impacting drug sensitivity, as well as the cyto-protective role of PARP-1 independent of its catalytic function are of interest to direct future efforts to clarify the mechanism of PARP-1-mediated sensitivity to the four agents. Taken together, these data suggest that PARP-1 plays an important role in the protection of cells to Yondelis®, Zalypsis®, PSL1, and PSL2, and suggest that PARP-1 status may determine the sensitivity or resistance of cells treated with these agents.
Book Synopsis DNA Recognition and Mechanistic Investigation of Poly(ADP-ribose) Polymerase-1 by : Meilan Wu
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.
Book Synopsis Poly(ADP-ribose) Polymerase by : Alexei V Tulin
Download or read book Poly(ADP-ribose) Polymerase written by Alexei V Tulin and published by Humana Press. This book was released on 2011-08-31 with total page 521 pages. Available in PDF, EPUB and Kindle. Book excerpt: Poly (ADP-ribose) Polymerases (PARPs) are abundant and ubiquitous proteins that regulate crucial processes of the cell cycle, DNA repair, genomic stability, and transcriptional regulation. Being involved in basic cell functions, PARPs mediate rapid responses to such environmental factors as stress, infection, nutrition and hormonal signals. Whereas PARP inhibitors can suppress tumor growth and proliferation in certain breast, ovarian, and prostate cancers, understanding how PARP controls cellular functions is essential for the development of novel cancer treatments strategies. Divided into three convenient sections, Poly(ADP-Ribose) Polymerase: Methods and Protocols aims to explain how PARP proteins act within the normal development of an organism as well as in pathogenic conditions, seeks to advance the knowledge of developmental pathways regulation, and endeavors to facilitate the development of new therapeutic drugs and methods to target PARP-dependent processes. Written in the highly successful Methods in Molecular BiologyTM series format, chapters contain introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and notes on troubleshooting and avoiding known pitfalls. Authoritative and accessible, Poly(ADP-Ribose) Polymerase: Methods and Protocols serves as an ideal guide to scientists who wish to continue exploring this exciting and progressive research field.
Book Synopsis Proteomics of Poly(ADP-ribose) Polymerases During DNA Replication and Repair by : Maria Tedim Ferreira
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.
Book Synopsis Signal Transduction in Cancer by : David A. Frank
Download or read book Signal Transduction in Cancer written by David A. Frank and published by Springer Science & Business Media. This book was released on 2002-12-31 with total page 358 pages. Available in PDF, EPUB and Kindle. Book excerpt: One of the most exciting areas of cancer research now is the development of agents which can target signal transduction pathways that are activated inappropriately in malignant cells. The understanding of the molecular abnormalities which distinguish malignant cells from their normal counterparts has grown tremendously. This volume summarizes the current research on the role that signal transduction pathways play in the pathogenesis of cancer and how this knowledge may be used to develop the next generation of more effective and less toxic anticancer agents. Series Editor comments: "The biologic behavior of both normal and cancer cells is determined by critical signal transduction pathways. This text provides a comprehensive review of the field. Leading investigators discuss key molecules that may prove to be important diagnostic and/or therapeutic targets."
Book Synopsis Poly(ADP-Ribosyl)ation by : Alexander Bürkle
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.
Book Synopsis Drug Resistance in Leukemia and Lymphoma III by : G.J.L. Kaspers
Download or read book Drug Resistance in Leukemia and Lymphoma III written by G.J.L. Kaspers and published by Springer Science & Business Media. This book was released on 1999-09-30 with total page 664 pages. Available in PDF, EPUB and Kindle. Book excerpt: Cellular drug resistance is a major limitation to the success of chemotherapy of leu kemia and lymphoma. The importance of this has now been recognized by both clinicians and scientists. It is of utmost importance to bridge the gap between laboratory and clinic in this field of research. This is the main purpose of the series of International Symposia on Drug Resistance in Leukemia and Lymphoma. These are held every three years in Am sterdam, The Netherlands, since 1992. This book contains the proceedings of the third of these meetings, organised in 1998. The book covers all important aspects of drug resistance in leukemia and lymphoma, both in the form of extensive reviews as in manuscripts describing original data. General mechanisms of resistance are discussed, including the drug resistance related proteins p glycoprotein, MRP (multi-drug resistance protein) and LRP (lung resistance protein), and the role of glutathione and glutathione-S-transferases. Moreover, more drug type-specific mechanisms of resistance are a topic, such as for glucocorticoids and antifolates. Much in formation is provided on apoptosis and its regulators, and on the results of cell culture drug resistance assays. Several papers focus on the modulation or circumvention of drug resistance.
Book Synopsis ADP-Ribose Transfer Reactions by : Myron K. Jacobson
Download or read book ADP-Ribose Transfer Reactions written by Myron K. Jacobson and published by Springer Science & Business Media. This book was released on 2012-12-06 with total page 543 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
Book Synopsis Introduction to Epigenetics by : Renato Paro
Download or read book Introduction to Epigenetics written by Renato Paro and published by Springer Nature. This book was released on 2021-03-23 with total page 215 pages. Available in PDF, EPUB and Kindle. Book excerpt: This open access textbook leads the reader from basic concepts of chromatin structure and function and RNA mechanisms to the understanding of epigenetics, imprinting, regeneration and reprogramming. The textbook treats epigenetic phenomena in animals, as well as plants. Written by four internationally known experts and senior lecturers in this field, it provides a valuable tool for Master- and PhD- students who need to comprehend the principles of epigenetics, or wish to gain a deeper knowledge in this field. After reading this book, the student will: Have an understanding of the basic toolbox of epigenetic regulation Know how genetic and epigenetic information layers are interconnected Be able to explain complex epigenetic phenomena by understanding the structures and principles of the underlying molecular mechanisms Understand how misregulated epigenetic mechanisms can lead to disease
Book Synopsis Poly(ADP-Ribose) Polymerase by : Alexei V. Tulin
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.
Book Synopsis Mitochondria and Cancer by : Keshav Singh
Download or read book Mitochondria and Cancer written by Keshav Singh and published by Springer Science & Business Media. This book was released on 2009-04-05 with total page 294 pages. Available in PDF, EPUB and Kindle. Book excerpt: Nearly a century of scientific research has revealed that mitochondrial dysfunction is one of the most common and consistent phenotypes of cancer cells. A number of notable differences in the mitochondria of normal and cancer cells have been described. These include differences in mitochondrial metabolic activity, molecular composition of mitochondria and mtDNA sequence, as well as in alteration of nuclear genes encoding mitochondrial proteins. This book, Mitochondria and Cancer, edited by Keshav K. Singh and Leslie C. Costello, presents thorough analyses of mitochondrial dysfunction as one of the hallmarks of cancer, discusses the clinical implications of mitochondrial defects in cancer, and as unique cellular targets for novel and selective anti-cancer therapy.
Book Synopsis Teratocarcinomas and Embryonic Stem Cells by : Elizabeth J. Robertson
Download or read book Teratocarcinomas and Embryonic Stem Cells written by Elizabeth J. Robertson and published by Oxford University Press, USA. This book was released on 1987 with total page 276 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Book Synopsis Viral Skin Diseases—Advances in Research and Treatment: 2013 Edition by :
Download or read book Viral Skin Diseases—Advances in Research and Treatment: 2013 Edition written by and published by ScholarlyEditions. This book was released on 2013-06-21 with total page 56 pages. Available in PDF, EPUB and Kindle. Book excerpt: Viral Skin Diseases—Advances in Research and Treatment: 2013 Edition is a ScholarlyBrief™ that delivers timely, authoritative, comprehensive, and specialized information about Herpes Simplex in a concise format. The editors have built Viral Skin Diseases—Advances in Research and Treatment: 2013 Edition on the vast information databases of ScholarlyNews.™ You can expect the information about Herpes Simplex in this book to be deeper than what you can access anywhere else, as well as consistently reliable, authoritative, informed, and relevant. The content of Viral Skin Diseases—Advances in Research and Treatment: 2013 Edition has been produced by the world’s leading scientists, engineers, analysts, research institutions, and companies. All of the content is from peer-reviewed sources, and all of it is written, assembled, and edited by the editors at ScholarlyEditions™ and available exclusively from us. You now have a source you can cite with authority, confidence, and credibility. More information is available at http://www.ScholarlyEditions.com/.
Book Synopsis Alternative Respiratory Pathways in Higher Plants by : Kapuganti Jagadis Gupta
Download or read book Alternative Respiratory Pathways in Higher Plants written by Kapuganti Jagadis Gupta and published by John Wiley & Sons. This book was released on 2015-06-15 with total page 398 pages. Available in PDF, EPUB and Kindle. Book excerpt: Rapid developments in molecular and systems biology techniques have allowed researchers to unravel many new mechanisms through which plant cells switch over to alternative respiratory pathways. This book is a unique compendium of how and why higher plants evolved alternative respiratory metabolism. It offers a comprehensive review of current research in the biochemistry, physiology, classification and regulation of plant alternative respiratory pathways, from alternative oxidase diversity to functional marker development. The resource provides a broad range of perspectives on the applications of plant respiratory physiology, and suggests brand new areas of research. Other key features: written by an international team of reputed plant physiologists, known for their pioneering contributions to the knowledge of regular and alternative respiratory metabolism in higher plants includes step-by-step protocols for key molecular and imaging techniques advises on regulatory options for managing crop yields, food quality and environment for crop improvement and enhanced food security covers special pathways which are of key relevance in agriculture, particularly in plant post-harvest commodities Primarily for plant physiologists and plant biologists, this authoritative compendium will also be of great value to postdoctoral researchers working on plant respiration, as well as to graduate and postgraduate students and university staff in Plant Science. It is a useful resource for corporate and private firms involved in developing functional markers for breeding programs and controlling respiration for the prevention of post-harvest losses in fruit, vegetables, cut flowers and tubers.
Book Synopsis Fundamentals of Chromatin by : Jerry L. Workman
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.
Book Synopsis Principles of Nutrigenetics and Nutrigenomics by : Raffaele De Caterina
Download or read book Principles of Nutrigenetics and Nutrigenomics written by Raffaele De Caterina and published by Academic Press. This book was released on 2019-09-22 with total page 586 pages. Available in PDF, EPUB and Kindle. Book excerpt: Principles of Nutrigenetics and Nutrigenomics: Fundamentals for Individualized Nutrition is the most comprehensive foundational text on the complex topics of nutrigenetics and nutrigenomics. Edited by three leaders in the field with contributions from the most well-cited researchers conducting groundbreaking research in the field, the book covers how the genetic makeup influences the response to foods and nutrients and how nutrients affect gene expression. Principles of Nutrigenetics and Nutrigenomics: Fundamentals for Individualized Nutrition is broken into four parts providing a valuable overview of genetics, nutrigenetics, and nutrigenomics, and a conclusion that helps to translate research into practice. With an overview of the background, evidence, challenges, and opportunities in the field, readers will come away with a strong understanding of how this new science is the frontier of medical nutrition. Principles of Nutrigenetics and Nutrigenomics: Fundamentals for Individualized Nutrition is a valuable reference for students and researchers studying nutrition, genetics, medicine, and related fields. Uniquely foundational, comprehensive, and systematic approach with full evidence-based coverage of established and emerging topics in nutrigenetics and nutrigenomics Includes a valuable guide to ethics for genetic testing for nutritional advice Chapters include definitions, methods, summaries, figures, and tables to help students, researchers, and faculty grasp key concepts Companion website includes slide decks, images, questions, and other teaching and learning aids designed to facilitate communication and comprehension of the content presented in the book
