The Multifaceted Role of Exonuclease 1 in DNA Repair and Adult Stem Cell Populations PDF Download
Are you looking for read ebook online? Search for your book and save it on your Kindle device, PC, phones or tablets. Download The Multifaceted Role of Exonuclease 1 in DNA Repair and Adult Stem Cell Populations PDF full book. Access full book title The Multifaceted Role of Exonuclease 1 in DNA Repair and Adult Stem Cell Populations by Amar Bharat Desai. Download full books in PDF and EPUB format.
Author: Amar Bharat Desai
Publisher:
ISBN:
Category : Adult stem cells
Languages : en
Pages : 168
Get Book Here
Book Description
The DNA damage response is composed of multiple signaling and repair pathways which together constitute an important tool cells utilize to preserve genomic stability. Repair pathways have shown to be critical in many cell types, including in human cancers where upregulation of DNA repair is believed to contribute to therapy resistance. In normal human development it is vital to stem cell populations, including in the hematopoietic system, where maintenance of genomic stability is necessary for development and normal immune function. The precise proteins and pathways responsible for maintaining cellular damage responses are often cell type specific, and identification of critical repair enzymes continues to yield promising therapeutic targets for a plethora of human conditions.The 5'->3' nuclease Exonuclease 1 (Exo1) has been implicated in several cellular processes including DNA mismatch and double strand break repair. Its upregulation has been characterized in human cancers of the breast, lung, colon, bladder and others. Here we examine the role of Exo1 in multiple contexts, including in hematopoietic stem cells (HSC), where we describe Exo1 loss in the HSC damage response both in quiescent and active settings. We demonstrate that while Exo1 and homologous recombination (HR) are dispensable for HSCs at steady state, stress induced cell cycle entry results in an HSC reliance on Exo1 mediated HR. We also explore the importance of DNA repair pathways and Exo1 in human lung cancer stem cells using the CD133 marker, and characterize the potential for Exo1 silencing as a cancer stem cell specific therapy. We find that upon prior exposure to double-strand break therapy, CD133+ cells are activated and rely on multiple DNA repair proteins including Exo1, and that this reliance contributes to radiation resistance. Finally we mechanistically describe the role of Exo1 in DNA Mismatch Repair (MMR) and identify a compensatory Exo1 independent pathway that cells adopt to minimize genomic instability involving the additional 5'-->3' nucleases Artemis, Fan1, and Mre11.Collectively our findings provide deeper insight into the DNA repair dependence of multiple stem cell populations and characterize the importance of Exonuclease 1 both in stem cell maintenance and as a potential therapeutic target.
Author: Amar Bharat Desai
Publisher:
ISBN:
Category : Adult stem cells
Languages : en
Pages : 168
Get Book Here
Book Description
The DNA damage response is composed of multiple signaling and repair pathways which together constitute an important tool cells utilize to preserve genomic stability. Repair pathways have shown to be critical in many cell types, including in human cancers where upregulation of DNA repair is believed to contribute to therapy resistance. In normal human development it is vital to stem cell populations, including in the hematopoietic system, where maintenance of genomic stability is necessary for development and normal immune function. The precise proteins and pathways responsible for maintaining cellular damage responses are often cell type specific, and identification of critical repair enzymes continues to yield promising therapeutic targets for a plethora of human conditions.The 5'->3' nuclease Exonuclease 1 (Exo1) has been implicated in several cellular processes including DNA mismatch and double strand break repair. Its upregulation has been characterized in human cancers of the breast, lung, colon, bladder and others. Here we examine the role of Exo1 in multiple contexts, including in hematopoietic stem cells (HSC), where we describe Exo1 loss in the HSC damage response both in quiescent and active settings. We demonstrate that while Exo1 and homologous recombination (HR) are dispensable for HSCs at steady state, stress induced cell cycle entry results in an HSC reliance on Exo1 mediated HR. We also explore the importance of DNA repair pathways and Exo1 in human lung cancer stem cells using the CD133 marker, and characterize the potential for Exo1 silencing as a cancer stem cell specific therapy. We find that upon prior exposure to double-strand break therapy, CD133+ cells are activated and rely on multiple DNA repair proteins including Exo1, and that this reliance contributes to radiation resistance. Finally we mechanistically describe the role of Exo1 in DNA Mismatch Repair (MMR) and identify a compensatory Exo1 independent pathway that cells adopt to minimize genomic instability involving the additional 5'-->3' nucleases Artemis, Fan1, and Mre11.Collectively our findings provide deeper insight into the DNA repair dependence of multiple stem cell populations and characterize the importance of Exonuclease 1 both in stem cell maintenance and as a potential therapeutic target.
Author: United States. Public Health Service. Office of the Surgeon General
Publisher:
ISBN:
Category : Government publications
Languages : en
Pages : 728
Get Book Here
Book Description
This report considers the biological and behavioral mechanisms that may underlie the pathogenicity of tobacco smoke. Many Surgeon General's reports have considered research findings on mechanisms in assessing the biological plausibility of associations observed in epidemiologic studies. Mechanisms of disease are important because they may provide plausibility, which is one of the guideline criteria for assessing evidence on causation. This report specifically reviews the evidence on the potential mechanisms by which smoking causes diseases and considers whether a mechanism is likely to be operative in the production of human disease by tobacco smoke. This evidence is relevant to understanding how smoking causes disease, to identifying those who may be particularly susceptible, and to assessing the potential risks of tobacco products.
Author: Paul A. Schulte
Publisher: Academic Press
ISBN: 0323138578
Category : Medical
Languages : en
Pages : 609
Get Book Here
Book Description
This book will serve as a primer for both laboratory and field scientists who are shaping the emerging field of molecular epidemiology. Molecular epidemiology utilizes the same paradigm as traditional epidemiology but uses biological markers to identify exposure, disease or susceptibility. Schulte and Perera present the epidemiologic methods pertinent to biological markers. The book is also designed to enumerate the considerations necessary for valid field research and provide a resource on the salient and subtle features of biological indicators.
Author: Bert W. O'Malley
Publisher:
ISBN:
Category : Cyclic nucleotides
Languages : en
Pages : 488
Get Book Here
Book Description
Hormone assays; Hormone receptors; Evaluation of biological effects of hormones; Purification and synthesis of hormones.
Author: Steven Howard
Publisher: Royal Society of Chemistry
ISBN: 1782625658
Category : Medical
Languages : en
Pages : 314
Get Book Here
Book Description
Fragment-based drug discovery is a rapidly evolving area of research, which has recently seen new applications in areas such as epigenetics, GPCRs and the identification of novel allosteric binding pockets. The first fragment-derived drug was recently approved for the treatment of melanoma. It is hoped that this approval is just the beginning of the many drugs yet to be discovered using this fascinating technique. This book is written from a Chemist's perspective and comprehensively assesses the impact of fragment-based drug discovery on a wide variety of areas of medicinal chemistry. It will prove to be an invaluable resource for medicinal chemists working in academia and industry, as well as anyone interested in novel drug discovery techniques.
Author: Mari Dezawa
Publisher: Springer
ISBN: 4431568476
Category : Medical
Languages : en
Pages : 315
Get Book Here
Book Description
This book provides the first comprehensive account of multilineage-differentiating stress-enduring (Muse) cells, a pluripotent and non-tumorigenic subpopulation of mesenchymal stem cells (MSCs) that have the ability to detect damage signals, migrate to damaged sites, and spontaneously differentiate into cells compatible with the affected tissue, thereby enabling repair of all tissue types. The coverage encompasses everything from the basic properties of Muse cells to their tissue repair effects and potential clinical applications—for example, in acute myocardial infarction, stroke, skin injuries and ulcers, renal failure, and liver disease. An important technical chapter provides a practical and precise protocol for the isolation of Muse cells, which will enable readers to use Muse cells in their own research. In offering fascinating insights into the strategic organization of the body’s reparative function and explaining how full utilization of Muse cells may significantly enhance the effectiveness of MSC treatment, the book will be of high value for Ph.D. students, postdocs, basic researchers, clinical doctors, and industrial developers.
Author: Francesca Storici
Publisher: Humana
ISBN: 9781493963218
Category : Medical
Languages : en
Pages : 0
Get Book Here
Book Description
Gene correction is a technology that gives us the tools for both repairing and mutating DNA, for discovering gene functions and for engineering new genetic variants. Gene Correction: Methods and Protocols provides a user friendly, detailed and up-to-date collection of strategies and methodologies utilized for generating specific sequence changes in the DNA of cells in the laboratory, while also tackling the major problems that the field of gene correction faces. This volume brings together many experts in the field of gene correction to disclose a wide and varied array of specific gene correction protocols for engineering mutations in DNA, for delivering correcting DNA to target cells, and for improving the accuracy and safety of the gene correction process. Written in the 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 protocols, and notes on troubleshooting and avoiding known pitfalls. Authoritative and easily accessible, Gene Correction: Methods and Protocols seeks to serve scientists of all backgrounds interested in the area of gene targeting/recombination/therapy.
Author: Mansi Arora
Publisher: Springer
ISBN: 981131568X
Category : Medical
Languages : en
Pages : 313
Get Book Here
Book Description
In the last decade, researchers working in the field of cancer biology have shifted their focus from genetic defects to epigenetic dysregulation, especially that of non-coding RNAs (ncRNAs). This book encompasses a comprehensive review of the transcriptional landscape of the cell and its involvement in the cancer pathophysiology. The first two chapters elucidate the basics of biosynthesis, mechanism of action and modulation of the epigenetic regulation of gene expression by coding as well as non-coding RNAs. The third chapter discusses the aberrant expression of the cellular RNome in the cancer cells and highlights its role in the orchestration of processes involved in evolution as well as the sustenance of cancer cells. The fourth chapter describes the recent advances in the field of translating the transcriptome into diagnostic/prognostic biomarkers and as targets for novel anti-cancer therapies. The final chapter then reviews the emerging experimental approaches to screen, identify and explore the functions of ncRNAs. Providing valuable insights into the field of RNome in the context of cancer, this book is helpful to students, researchers and clinicians..
Author: Keiko Hiyama
Publisher: Springer Science & Business Media
ISBN: 1603278796
Category : Medical
Languages : en
Pages : 375
Get Book Here
Book Description
Telomerase, an enzyme that maintains telomeres and endows eukaryotic cells with immortality, was first discovered in tetrahymena in 1985. In 1990s, it was proven that this enzyme also plays a key role in the infinite proliferation of human cancer cells. Now telomere and telomerase are widely accepted as important factors involved in cancer biology, and as promising diagnostic tools and therapeutic targets. Recently, role of telomerase in “cancer stem cells” has become another attractive story. Until now, there are several good books on telomere and telomerase focusing on biology in ciliates, yeasts, and mouse or basic sciences in human, providing basic scientists or students with updated knowledge.
Author: David Mittelman
Publisher: Springer Science & Business Media
ISBN: 1461462800
Category : Medical
Languages : en
Pages : 284
Get Book Here
Book Description
The discovery of stress-induced mutagenesis has changed ideas about mutation and evolution, and revealed mutagenic programs that differ from standard spontaneous mutagenesis in rapidly proliferating cells. The stress-induced mutations occur during growth-limiting stress, and can include adaptive mutations that allow growth in the otherwise growth-limiting environment. The stress responses increase mutagenesis specifically when cells are maladapted to their environments, i.e. are stressed, potentially accelerating evolution then. The mutation mechanism also includes temporary suspension of post-synthesis mismatch repair, resembling mutagenesis characteristic of some cancers. Stress-induced mutation mechanisms may provide important models for genome instability underlying some cancers and genetic diseases, resistance to chemotherapeutic and antibiotic drugs, pathogenicity of microbes, and many other important evolutionary processes. This book covers pathways of stress-induced mutagenesis in all systems. The principle focus is mammalian systems, but much of what is known of these pathways comes from non-mammalian systems.
