Download or read book A Genome wide SiRNA Screen Reveals Diverse Cellular Processes and Pathways that Mediate Genomic Stability written by Renee Darlene Paulsen and published by . This book was released on 2010 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: Genome instability has long been known to be a hallmark of cancerous cells, but the cellular causes and consequences of such instability are still not fully understood. Mutations, translocations, DNA rearrangements, as well as chromosomal loss can all result in the loss of genomic integrity. To prevent the disruption of cellular homeostasis due to DNA damage accumulation, cells contain pathways to sense and respond to DNA damage including cell cycle checkpoints and numerous DNA repair processes, collectively known as the DNA damage response (DDR). Mutations in many of the genes involved in the DDR are linked to several diseases, including premature aging, neurodegeneration and cancer. These signaling pathways are especially critical during DNA replication when the DNA is unwound and vulnerable to processing. Here, the cell relies on the S-phase checkpoint to sense DNA damage at the sites of replication forks and to facilitate a number of downstream pathways to maintain genomic stability. These processes include blocking further origin firing, facilitating DNA repair, preventing cell cycle progression, and stabilizing stalled replication forks. Here, two genome-wide siRNA screens were employed to identify additional genes involved in genome stabilization by monitoring phosphorylation of the histone variant H2AX, an early mark of DNA damage. The first screen looked at H2AX phosphorylation that occurred simply by individual protein depletion, and the second screen used a low level of a replication inhibitor, aphidicolin, to specifically identify genes that were needed to prevent DNA damage during S-phase, potentially due to the loss of replication fork stabilization mechanisms. While the results from the second screen are still undergoing further characterization, we did discover hundreds of genes whose down-regulation led to elevated levels of H2AX phosphorylation in the absence of any external stress. From this gene set, we identified many gene networks that were significantly enriched amongst our screening hits as well as several intriguing individual genes that were chosen for follow up study. These included genes involved in mRNA processing, the pathology of Charcot-Marie-Tooth syndrome, and the histone methyl transferase protein, Set8.

Download or read book A Genome wide SiRNA Screen Identifies a Novel 7 Transmembrane Protein that Mediates Amino Acid Signaling to MTORC1 written by Lin Gan and published by . This book was released on 2013 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: Cells have an evolutionarily conserved mechanism to sense and integrate nutrient information for optimal growth and survival. The signaling network that is central to receiving nutritional inputs and translating them to effects on anabolic and catabolic activities of the cell consists of a large serine/threonine kinase known as mTOR. mTOR signaling is crucial for many important cellular processes such metabolism, growth, proliferation and differentiation. It is able to integrate diverse inputs including growth factors, cytokines, energy, oxygen and stress in addition to nutrients and regulate diverse outputs including translation, ribosome biogenesis, lipid biogenesis and autophagy. It is also an important therapeutic target and its inhibitor Rapamycin is currently being used or tested for a wide range of diseases including cancers and neurodegenerative diseases. Amino acids are arguably the most important regulators of mTOR and a long standing mystery in the field is the identity of the amino acid sensor and the mechanism of sensing. Using RNAi, we systematically screened through the human genome for candidate genes regulating amino acid signaling. We confirm that the mitochondria and the lysosomes are the two key sensing organelles, with amino acid metabolism and the RagGTPases being important for signal transduction. We identify a novel lysosomal 7 transmembrane protein that mediates signals upstream the RagGTPases and binds mTORC1-RagA in an amino-acid dependent manner. We also demonstrate that increasing levels of this protein enables cells to recruit mTOR to lysosomes and activate its kinase activity in the absence of amino acids. We show that GPR137B, mTORC1 and RagA form an amino acid sensitive, high-affinity binding complex at the lysosome. We propose a model of sensing where the 7-transmembrane protein, which we renamed to MORTOR, forms a tight complex with mTORC1-RagA in the presence of amino acids, resulting in the persistent lysosomal recruitment and activation of mTORC1. In addition to identifying novel regulators, this systematic study has also generated testable hypotheses about systems level properties of mTORC1 signaling, thus providing the foundation to understand mTOR signaling as a network. The discovery of the novel 7 transmembrane protein and its GPCR-like characteristics also has the potential to lead to new classes of therapeutics and targets for this important pathway.

Download or read book Toxicogenomics Based Cellular Models written by Jos Kleinjans and published by Academic Press. This book was released on 2014-01-02 with total page 367 pages. Available in PDF, EPUB and Kindle. Book excerpt: Toxicogenomics-Based Cellular Models is a unique and valuable reference for all academic and professional researchers employing toxicogenomic methods with respect to animal testing for chemical safety. This resource offers cutting-edge information on the application of toxicogenomics to developing alternatives to current animal toxicity tests. By illustrating the development of toxicogenomics-based cellular models for critical endpoints of toxicity and providing real-world examples for validation and data analysis, this book provides an assessment of the current state of the field, as well as opportunities and challenges for the future. Written by renowned international toxicological experts, this book explores 'omics technology for developing new assays for toxicity testing and safety assessment and provides the reader with a focused examination of alternative means to animal testing. - Describes the state-of-the-art in developing toxicogenomics-based cellular models for chemical-induced carcinogenicity, immunotoxicity, developmental toxicity, neurotoxicity and reproduction toxicity - Illustrates how to validate toxicogenomics-based alternative test models and provides an outlook to societal and economic implementation of these novel assays - Includes an overview of current testing methods and risk assessment frameworks - Provides a real-world assessment by articulating the current development and challenges in toxicogenomics while suggesting ways to move this field forward

Download or read book Endonuclease independent LINE 1 Retrotransposition written by Tammy A. Morrish and published by . This book was released on 2005 with total page 520 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book The Molecular Basis of Cancer written by John Mendelsohn and published by Elsevier Health Sciences. This book was released on 2014-02-20 with total page 1040 pages. Available in PDF, EPUB and Kindle. Book excerpt: 2015 BMA Medical Book Awards Highly Commended in Oncology Category!The Molecular Basis of Cancer arms you with the latest knowledge and cutting-edge advances in the battle against cancer. This thoroughly revised, comprehensive oncology reference explores the scientific basis for our current understanding of malignant transformation and the pathogenesis and treatment of this disease. A team of leading experts thoroughly explains the molecular biologic principles that underlie the diagnostic tests and therapeutic interventions now being used in clinical trials and practice. Detailed descriptions of topics from molecular abnormalities in common cancers to new approaches for cancer therapy equip you to understand and apply the complexities of ongoing research in everyday clinical application. Effectively determine the course of malignancy and design appropriate treatment protocols by understanding the scientific underpinnings of cancer. Visually grasp and retain difficult concepts easily thanks to a user-friendly format with abundant full-color figures. Find critical information quickly with chapters following a logical sequence that moves from pathogenesis to therapy. Stay current with the latest discoveries in molecular and genomic research. Sweeping revisions throughout include eight brand-new chapters on: Tumor Suppressor Genes; Inflammation and Cancer; Cancer Systems Biology: The Future; Biomarkers Assessing Risk of Cancer; Understanding and Using Information About Cancer Genomes; The Technology of Analyzing Nucleic Acids in Cancer; Molecular Abnormalities in Kidney Cancer; and Molecular Pathology. Access the entire text and illustrations online, fully searchable, at Expert Consult.

Download or read book Mechanisms of DNA Repair written by Paul Doetsch and published by Academic Press. This book was released on 2012-07-17 with total page 354 pages. Available in PDF, EPUB and Kindle. Book excerpt: Mechanisms of DNA Repair.

Download or read book DNA Recombination and Repair written by Paul James Smith and published by Oxford University Press, USA. This book was released on 1999 with total page 260 pages. Available in PDF, EPUB and Kindle. Book excerpt: The processes of DNA recombination and repair are vital to cell integrity - an error can lead to disease such as cancer. It is therefore a large and exciting area of research and is also taught on postgraduate and undergraduate courses. This book is not a comprehensive view of the field, but a selection of the issues currently at the forefront of knowledge.

Download or read book Disease and the Hippo Pathway written by Carsten Gram Hansen and published by MDPI. This book was released on 2019-11-22 with total page 226 pages. Available in PDF, EPUB and Kindle. Book excerpt: The Hippo pathway is a highly dynamic cellular signaling nexus that plays central roles in multiple cell types and regulates regeneration, metabolism, and development. The Hippo pathway integrates mechanotransduction, cell polarity, inflammation, and numerous types of paracrine signaling. If not tightly regulated, dysregulated Hippo pathway signaling drives the onset and progression of a range of diseases, including fibrosis and cancer. The molecular understanding of the Hippo pathway is rapidly evolving. This Special Issue contains ten articles contributed by established and up-and-coming Hippo pathway experts that, as a whole, provides an up-to-date overview of how dysregulated Hippo pathway activity is a common driver of specific diseases. The articles have a particular focus on the underlying molecular and cellular mechanisms that cause the Hippo pathway to go awry, and especially how this drives disease. The articles analyze disease-specific as well as common themes, which provides valuable insights into the fundamental molecular mechanisms in the dysfunctioning Hippo pathway, and thereby offer practical insights into potential future therapeutic intervention strategies.

Download or read book DNA Repair and Replication written by Roger J. A. Grand and published by Garland Science. This book was released on 2018-09-03 with total page 672 pages. Available in PDF, EPUB and Kindle. Book excerpt: DNA Repair and Replication brings together contributions from active researchers. The first part of this book covers most aspects of the DNA damage response, emphasizing the relationship to replication stress. The second part concentrates on the relevance of this to human disease, with particular focus on both the causes and treatments which make use of DNA Damage Repair (DDR) pathways. Key Selling Features: Chapters written by leading researchers Includes description of replication processes, causes of damage, and methods of repair

Download or read book The Initiation of DNA Replication in Eukaryotes written by Daniel L. Kaplan and published by Springer. This book was released on 2016-02-11 with total page 564 pages. Available in PDF, EPUB and Kindle. Book excerpt: ​Every time a cell divides, a copy of its genomic DNA has to be faithfully copied to generate new genomic DNA for the daughter cells. The process of DNA replication needs to be precisely regulated to ensure that replication of the genome is complete and accurate, but that re-replication does not occur. Errors in DNA replication can lead to genome instability and cancer. The process of replication initiation is of paramount importance, because once the cell is committed to replicate DNA, it must finish this process. A great deal of progress has been made in understanding how DNA replication is initiated in eukaryotic cells in the past ten years, but this is the first one-source book on these findings. The Initiation of DNA Replication in Eukaryotes will focus on how DNA replication is initiated in eukaryotic cells. While the concept of replication initiation is simple, its elaborate regulation and integration with other cell processes results in a high level of complexity. This book will cover how the position of replication initiation is chosen, how replication initiation is integrated with the phases of the cell cycle, and how it is regulated in the case of damage to DNA. It is the cellular protein machinery that enables replication initiation to be activated and regulated. We now have an in-depth understanding of how cellular proteins work together to start DNA replication, and this new resource will reveal a mechanistic description of DNA replication initiation as well.

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 Dynamics of Mathematical Models in Biology written by Alessandra Rogato and published by Springer. This book was released on 2016-11-03 with total page 154 pages. Available in PDF, EPUB and Kindle. Book excerpt: This volume focuses on contributions from both the mathematics and life science community surrounding the concepts of time and dynamicity of nature, two significant elements which are often overlooked in modeling process to avoid exponential computations. The book is divided into three distinct parts: dynamics of genomes and genetic variation, dynamics of motifs, and dynamics of biological networks. Chapters included in dynamics of genomes and genetic variation analyze the molecular mechanisms and evolutionary processes that shape the structure and function of genomes and those that govern genome dynamics. The dynamics of motifs portion of the volume provides an overview of current methods for motif searching in DNA, RNA and proteins, a key process to discover emergent properties of cells, tissues, and organisms. The part devoted to the dynamics of biological networks covers networks aptly discusses networks in complex biological functions and activities that interpret processes in cells. Moreover, chapters in this section examine several mathematical models and algorithms available for integration, analysis, and characterization. Once life scientists began to produce experimental data at an unprecedented pace, it become clear that mathematical models were necessary to interpret data, to structure information with the aim to unveil biological mechanisms, discover results, and make predictions. The second annual “Bringing Maths to Life” workshop held in Naples, Italy October 2015, enabled a bi-directional flow of ideas from and international group of mathematicians and biologists. The venue allowed mathematicians to introduce novel algorithms, methods, and software that may be useful to model aspects of life science, and life scientists posed new challenges for mathematicians.

Download or read book Alternative Splicing Regulation in Plants written by Ezequiel Petrillo and published by Frontiers Media SA. This book was released on 2020-09-02 with total page 175 pages. Available in PDF, EPUB and Kindle. Book excerpt: This eBook is a collection of articles from a Frontiers Research Topic. Frontiers Research Topics are very popular trademarks of the Frontiers Journals Series: they are collections of at least ten articles, all centered on a particular subject. With their unique mix of varied contributions from Original Research to Review Articles, Frontiers Research Topics unify the most influential researchers, the latest key findings and historical advances in a hot research area! Find out more on how to host your own Frontiers Research Topic or contribute to one as an author by contacting the Frontiers Editorial Office: frontiersin.org/about/contact.

Download or read book Oncogene and Cancer written by Yahwardiah Siregar and published by Inst za onkologiju i radiol. This book was released on 2013-01-24 with total page 497 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book describes a course of cancer growth starting from normal cells to cancerous form and the genomic instability, the cancer treatment as well as its prevention in form of the invention of a vaccine. Some diseases are also discussed in detail, such as breast cancer, leucaemia, cervical cancer, and glioma. Understanding cancer through its molecular mechanism is needed to reduce the cancer incidence. How to treat cancer more effectively and the problems like drug resistance and metastasis are very clearly illustrated in this publication as well as some research result that could be used to treat the cancer patients in the very near future. The book was divided into six main sections: 1. HER2 Carcinogenesis: Etiology, Treatment and Prevention; 2. DNA Repair Mechanism and Cancer; 3. New Approach to Cancer Mechanism; 4. New Role of Oncogenes and Tumor Suppressor Genes; 5. Non Coding RNA and Micro RNA in Tumorigenesis; 6. Oncogenes for Transcription Factors

Download or read book Regulation of DNA Double Strand Break Repair by Local Chromatin Architecture written by Sérgio Fernandes de Almeida and published by Frontiers Media SA. This book was released on 2020-09-02 with total page 117 pages. Available in PDF, EPUB and Kindle. Book excerpt: This eBook is a collection of articles from a Frontiers Research Topic. Frontiers Research Topics are very popular trademarks of the Frontiers Journals Series: they are collections of at least ten articles, all centered on a particular subject. With their unique mix of varied contributions from Original Research to Review Articles, Frontiers Research Topics unify the most influential researchers, the latest key findings and historical advances in a hot research area! Find out more on how to host your own Frontiers Research Topic or contribute to one as an author by contacting the Frontiers Editorial Office: frontiersin.org/about/contact.

Download or read book Regulation of Alternative Splicing written by Philippe Jeanteur and published by . This book was released on 2014-01-15 with total page 266 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Genetically Engineered Crops written by National Academies of Sciences, Engineering, and Medicine and published by National Academies Press. This book was released on 2017-01-28 with total page 607 pages. Available in PDF, EPUB and Kindle. Book excerpt: Genetically engineered (GE) crops were first introduced commercially in the 1990s. After two decades of production, some groups and individuals remain critical of the technology based on their concerns about possible adverse effects on human health, the environment, and ethical considerations. At the same time, others are concerned that the technology is not reaching its potential to improve human health and the environment because of stringent regulations and reduced public funding to develop products offering more benefits to society. While the debate about these and other questions related to the genetic engineering techniques of the first 20 years goes on, emerging genetic-engineering technologies are adding new complexities to the conversation. Genetically Engineered Crops builds on previous related Academies reports published between 1987 and 2010 by undertaking a retrospective examination of the purported positive and adverse effects of GE crops and to anticipate what emerging genetic-engineering technologies hold for the future. This report indicates where there are uncertainties about the economic, agronomic, health, safety, or other impacts of GE crops and food, and makes recommendations to fill gaps in safety assessments, increase regulatory clarity, and improve innovations in and access to GE technology.