Genome Stability

Genome Stability: DNA Repair and Recombination describes the various mechanisms of repairing DNA damage by recombination, most notably the repair of chromosomal breaks. The text presents a definitive history of the evolution of molecular models of DNA repair, emphasizing current research. The book introduces the central players in recombination. An

Genome Stability: From Virus to Human Application, Second Edition, a volume in the Translational Epigenetics series, explores how various species maintain genome stability and genome diversification in response to environmental factors. Here, across thirty-eight chapters, leading researchers provide a deep analysis of genome stability in DNA/RNA viruses, prokaryotes, single cell eukaryotes, lower multicellular eukaryotes, and mammals, examining how epigenetic factors contribute to genome stability and how these species pass memories of encounters to progeny. Topics also include major DNA repair mechanisms, the role of chromatin in genome stability, human diseases associated with genome instability, and genome stability in response to aging. This second edition has been fully revised to address evolving research trends, including CRISPRs/Cas9 genome editing; conventional versus transgenic genome instability; breeding and genetic diseases associated with abnormal DNA repair; RNA and extrachromosomal DNA; cloning, stem cells, and embryo development; programmed genome instability; and conserved and divergent features of repair. This volume is an essential resource for geneticists, epigeneticists, and molecular biologists who are looking to gain a deeper understanding of this rapidly expanding field, and can also be of great use to advanced students who are looking to gain additional expertise in genome stability. A deep analysis of genome stability research from various kingdoms, including epigenetics and transgenerational effects Provides comprehensive coverage of mechanisms utilized by different organisms to maintain genomic stability Contains applications of genome instability research and outcomes for human disease Features all-new chapters on evolving areas of genome stability research, including CRISPRs/Cas9 genome editing, RNA and extrachromosomal DNA, programmed genome instability, and conserved and divergent features of repair

Since the establishment of the DNA structure researchers have been highly interested in the molecular basis of the inheritance of genes and of genetic disorders. Scientific investigations of the last two decades have shown that, in addition to oncogenic viruses and signalling pathways alterations, genomic instability is important in the development of cancer. This view is supported by the findings that aneuploidy, which results from chromosome instability, is one of the hallmarks of cancer cells. Chromosomal instability also underpins our fundamental principles of understanding tumourigenesis: It thought that cancer arises from the sequential acquisition of genetic alterations in specific genes. In this hypothesis, these rare genetic events represent rate-limiting ‘bottlenecks’ in the clonal evolution of a cancer, and pre-cancerous cells can evolve into neoplastic cells through the acquisition of somatic mutations. This book is written by international leading scientists in the field of genome stability. Chapters are devoted to genome stability and anti-cancer drug targets, histone modifications, chromatin factors, DNA repair, apoptosis and many other key areas of research. The chapters give insights into the newest development of the genome stability and human diseases and bring the current understanding of the mechanisms leading to chromosome instability and their potential for clinical impact to the reader.

The human genome, as with the genome of most organisms, is comprised of various types of mobile genetic element derived repeats. Mobile genetic elements that mobilize by an RNA intermediate, include both autonomous and non-autonomous retrotransposons, and mobilize by a “copy and paste” mechanism that relies of the presence of a functional reverse transcriptase activity. The extent to which these different types of elements are actively mobilizing varies among organisms, as revealed with the advent of Next Generation DNA sequencing (NGS). To understand the normal and aberrant mechanisms that impact the mobility of these elements requires a more extensive understanding of how these elements interact with molecular pathways of the cell, including DNA repair, recombination and chromatin. In addition, epigenetic based-mechanisms can also influence the mobility of these elements, likely by transcriptional activation or repression in certain cell types. Studies regarding how mobile genetic elements interface and evolve with these pathways will rely on genomic studies from various model organisms. In addition, the mechanistic details of how these elements are regulated will continue to be elucidated with the use of genetic, biochemical, molecular, cellular, and bioinformatic approaches. Remarkably, the current understanding regarding the biology of these elements in the human genome, suggests these elements may impact developmental biology, including cellular differentiation, neuronal development, and immune function. Thus, aberrant changes in these molecular pathways may also impact disease, including neuronal degeneration, autoimmunity, and cancer.

Epigenetics and Systems Biology highlights the need for collaboration between experiments and theoretical modeling that is required for successful application of systems biology in epigenetics studies. This book breaks down the obstacles which exist between systems biology and epigenetics researchers due to information barriers and segmented research, giving real-life examples of successful combinations of systems biology and epigenetics experiments. Each section covers one type of modeling and one set of epigenetic questions on which said models have been successfully applied. In addition, the book highlights how modeling and systems biology relate to studies of RNA, DNA, and genome instability, mechanisms of DNA damage signaling and repair, and the effect of the environment on genome stability. Presents original research in a wider perspective to reveal potential for synergies between the two fields of study Provides the latest experiments in primary literature for the modeling audience Includes chapters written by experts in systems biology and epigenetics who have vast experience studying clinical applications

An overview of the current systems biology-based knowledge and the experimental approaches for deciphering the biological basis of cancer.

Cancer and other genetic human diseases are caused by a variety of mutations, ranging from subtle sequence changes to larger genomic rearrangements and alterations in chromosome number (aneuploidy). With contributions by reputed experts, this book aims to update the knowledge on the multiple mechanisms of genomic instability leading to human disease. Emphasis is given to the different types of genomic sequences involved in disease-related genomic rearrangements as well as to the various exogenous factors increasing the frequency of mutations. Several chapters are dedicated to the dysfunction of important cellular mechanisms like DNA repair and chromosome segregation, which may cause genomic instability and result in tumorigenesis. Important 'caretaker' genes controlling the stability of our genome have been identified through their defect in genomic instability syndromes, which are also extensively reviewed in this volume. This book provides an important update not only for investigators in biology and medicine, but also for physicians and anyone interested in the molecular basis of human disease.

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

In the first edition of Genetics and Molecular Biology, renowned researcher and award-winning teacher Robert Schleif produced a unique and stimulating text that was a notable departure from the standard compendia of facts and observations. Schleif's strategy was to present the underlying fundamental concepts of molecular biology with clear explanations and critical analysis of well-chosen experiments. The result was a concise and practical approach that offered students a real understanding of the subject. This second edition retains that valuable approach--with material thoroughly updated to include an integrated treatment of prokaryotic and eukaryotic molecular biology. Genetics and Molecular Biology is copiously illustrated with two-color line art. Each chapter includes an extensive list of important references to the primary literature, as well as many innovative and thought-provoking problems on material covered in the text or on related topics. These help focus the student's attention of a variety of critical issues. Solutions are provided for half of the problems. Praise for the first edition: "Schleif's Genetics and Molecular Biology... is a remarkable achievement. It is an advanced text, derived from material taught largely to postgraduates, and will probably be thought best suited to budding professionals in molecular genetics. In some ways this would be a pity, because there is also gold here for the rest of us... The lessons here in dealing with the information explosion in biology are that an ounce of rationale is worth a pound of facts and that, for educational value, there is nothing to beat an author writing about stuff he knows from theinside."--Nature. "Schleif presents a quantitative, chemically rigorous approach to analyzing problems in molecular biology. The text is unique and clearly superior to any currently available."--R.L. Bernstein, San Francisco State University. "The greatest strength is the author's ability to challenge the student to become involved and get below the surface."--Clifford Brunk, UCLA

DNA Methylation and Complex Human Disease reviews the possibilities of methyl-group-based epigenetic biomarkers of major diseases, tailored epigenetic therapies, and the future uses of high-throughput methylome technologies. This volume includes many pertinent advances in disease-bearing research, including obesity, type II diabetes, schizophrenia, and autoimmunity. DNA methylation is also discussed as a plasma and serum test for non-invasive screening, diagnostic and prognostic tests, as compared to biopsy-driven gene expression analysis, factors which have led to the use of DNA methylation as a potential tool for determining cancer risk, and diagnosis between benign and malignant disease. Therapies are at the heart of this volume and the possibilities of DNA demethylation. In cancer, unlike genetic mutations, DNA methylation and histone modifications are reversible and thus have shown great potential in the race for effective treatments. In addition, the authors present the importance of high-throughput methylome analysis, not only in cancer, but also in non-neoplastic diseases such as rheumatoid arthritis. Discusses breaking biomarker research in major disease families of current health concern and research interest, including obesity, type II diabetes, schizophrenia, and autoimmunity Summarizes advances not only relevant to cancer, but also in non-neoplastic disease, currently an emerging field Describes wholly new concepts, including the linking of metabolic pathways with epigenetics Provides translational researchers with the knowledge of both basic research and clinic applications of DNA methylation in human diseases

Mismatch repair (MMR) systems correct mismatches formed during DNA replication and genetic recombination and as the result of DNA damage. MMR is initiated by a conserved family of MutS (MSH) and MutL (MLH) homolog proteins. MLH1 is unique among these proteins because it is also required for high levels of crossing over which are necessary for the proper disjunction of homologous chromosomes during the first meiotic division.

Written by an international team of experts, Somatic Genome Variation presents a timely summary of the latest understanding of somatic genome development and variation in plants, animals, and microorganisms. Wide-ranging in coverage, the authors provide an updated view of somatic genomes and genetic theories while also offering interpretations of somatic genome variation. The text provides geneticists, bioinformaticians, biologist, plant scientists, crop scientists, and microbiologists with a valuable overview of this fascinating field of research.

This book discusses advances in our understanding of the structure and function of the maize genome since publication of the original B73 reference genome in 2009, and the progress in translating this knowledge into basic biology and trait improvement. Maize is an extremely important crop, providing a large proportion of the world’s human caloric intake and animal feed, and serving as a model species for basic and applied research. The exceptionally high level of genetic diversity within maize presents opportunities and challenges in all aspects of maize genetics, from sequencing and genotyping to linking genotypes to phenotypes. Topics covered in this timely book range from (i) genome sequencing and genotyping techniques, (ii) genome features such as centromeres and epigenetic regulation, (iii) tools and resources available for trait genomics, to (iv) applications of allele mining and genomics-assisted breeding. This book is a valuable resource for researchers and students interested in maize genetics and genomics.

Abstract: This book presents contemporary information on mutagenesis in plants and its applications in plant breeding and research. The topics are classified into sections focusing on the concepts, historical development and genetic basis of plant mutation breeding (chapters 1-6); mutagens and induced mutagenesis (chapters 7-13); mutation induction and mutant development (chapters 14-23); mutation breeding (chapters 24-34); or mutations in functional genomics (chapters 35-41). This book is an essential reference for those who are conducting research on mutagenesis as an approach to improving or modifying a trait, or achieving basic understanding of a pathway for a trait --.

This book brings together in one volume the current state of ageing research in the nematode Caenorhabditis elegans. The authors are leading researchers in the field, placing this topic in the context of human ageing, describing how and why basic discoveries in this simple organism have impacted our prospects for intervention in the ageing process. The authors cover a broad range of topics with regards to organismal and reproductive ageing including anatomical, physiological and biochemical changes, as well as genetic and environmental interventions that promote longevity and ameliorate age-related disease. Ageing is the single most important factor determining the onset of human disease in developed countries. With current worldwide demographic trends indicating that the number of individuals over the age of 65 will continue to rise, it is clear that an understanding of the processes that underpin ageing and age-related disease represents a key challenge in the biomedical sciences. In recent years there have been huge advances in our understanding of the ageing process and many of these have stemmed from genetic analysis of C. elegans. With no analogous book in this subject area this work will be of interest to a wide audience, ranging from academic researchers to the general public.

This is the first book to give a full overview on genome integrity in different species. From microorganisms to humans, this volume provides an interdisciplinary overview of how genome integrity is maintained. Written by an international panel of experts, the book addresses the connection between genome integrity and human disease.

"Genome Stability: DNA Repair and Recombination describes the various mechanisms of repairing DNA damage by recombination, most notably the repair of chromosomal breaks. The text presents a definitive history of the evolution of molecular models of DNA repair, emphasizing current research. The book introduces the central players in recombination. An overview of the four major pathways of homologous recombinational repair is followed by a description of the several mechanisms of nonhomologous end-joining. Designed as a textbook for advanced undergraduate and graduate students with a molecular biology and genetics background, researchers and practitioners, especially in cancer biology, will also appreciate the book as a reference"--Provided by publisher.