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.
An "age" has passed in the 40 years since we first observed recovery from radiation damage in irradiated bacteria. During the early 1930s, we had been discussing the possibility of rapid changes after radiation exposure with Farring ton Daniels, Benjamin Duggar, John Curtis, and others at the University of Wisconsin. After working with living cells, we had concluded that organisms receiving massive insults must have a wide variety of repair mechanisms available for restoration of at least some of the essential properties of the cell. The problem was how to fmd and identify these recovery phenomena. At that time I was working on a problem considered to be of great importance-the existence of the so-called mitogenetic rays. Several hundred articles and a score of books had already appeared dealing with mitogenetic rays, a type of radiation that was thought to exist in the shorter ultraviolet region. Our search for mitogenetic rays necessitated the design of experiments of greatest sensitivity for the detection of ultraviolet. It was vital that conditions be kept as constant as possible during exposure. All the work was done at icewater temperature (3-5°C) during and after exposure. We knew that light was an important factor for cell recovery, so all our experiments were done in dim light, with the plated-out cells being covered with dark cloth. Our statements on the effect of visible light stimulated Kelner to search for "photoreactivation' (as it was later called).
Bacteria in various habitats are subject to continuously changing environmental conditions, such as nutrient deprivation, heat and cold stress, UV radiation, oxidative stress, dessication, acid stress, nitrosative stress, cell envelope stress, heavy metal exposure, osmotic stress, and others. In order to survive, they have to respond to these conditions by adapting their physiology through sometimes drastic changes in gene expression. In addition they may adapt by changing their morphology, forming biofilms, fruiting bodies or spores, filaments, Viable But Not Culturable (VBNC) cells or moving away from stress compounds via chemotaxis. Changes in gene expression constitute the main component of the bacterial response to stress and environmental changes, and involve a myriad of different mechanisms, including (alternative) sigma factors, bi- or tri-component regulatory systems, small non-coding RNA’s, chaperones, CHRIS-Cas systems, DNA repair, toxin-antitoxin systems, the stringent response, efflux pumps, alarmones, and modulation of the cell envelope or membranes, to name a few. Many regulatory elements are conserved in different bacteria; however there are endless variations on the theme and novel elements of gene regulation in bacteria inhabiting particular environments are constantly being discovered. Especially in (pathogenic) bacteria colonizing the human body a plethora of bacterial responses to innate stresses such as pH, reactive nitrogen and oxygen species and antibiotic stress are being described. An attempt is made to not only cover model systems but give a broad overview of the stress-responsive regulatory systems in a variety of bacteria, including medically important bacteria, where elucidation of certain aspects of these systems could lead to treatment strategies of the pathogens. Many of the regulatory systems being uncovered are specific, but there is also considerable “cross-talk” between different circuits. Stress and Environmental Regulation of Gene Expression and Adaptation in Bacteria is a comprehensive two-volume work bringing together both review and original research articles on key topics in stress and environmental control of gene expression in bacteria. Volume One contains key overview chapters, as well as content on one/two/three component regulatory systems and stress responses, sigma factors and stress responses, small non-coding RNAs and stress responses, toxin-antitoxin systems and stress responses, stringent response to stress, responses to UV irradiation, SOS and double stranded systems repair systems and stress, adaptation to both oxidative and osmotic stress, and desiccation tolerance and drought stress. Volume Two covers heat shock responses, chaperonins and stress, cold shock responses, adaptation to acid stress, nitrosative stress, and envelope stress, as well as iron homeostasis, metal resistance, quorum sensing, chemotaxis and biofilm formation, and viable but not culturable (VBNC) cells. Covering the full breadth of current stress and environmental control of gene expression studies and expanding it towards future advances in the field, these two volumes are a one-stop reference for (non) medical molecular geneticists interested in gene regulation under stress.
For over half a century, we have been in the thrall of the double-helicaln structure of DNA, which, in an instant, revealed that information can be transferred between generations by a simple rule, A pairs with T, G pairs with C. In its beautiful simplicity, this structure, along with the table of codons worked out in the following decade, had entranced us into believing that we can fully understand the information content of a DNA sequence, simply by treating it as text that is read in a linear fashion. While we have learned much based on this assumption, there is much we have missed. Far from a passive tape running through a reader, genomes contain information that appears in new forms which create regions with distinct behavior. Some are "gene rich", some mobile, some full of repeats and duplications, some sticking together across long evolutionary distances, some readily breaking apart in tumor cells. Even protein-coding regions can carry additional information, taking advantage of the flexible coding options provided by the degeneracy of the genetic code. The chapters in this volume touch on one or more of three interconnected themes; information can be implied, rather than explicit, in a genome; information can lead to focused and/or regulated changes in nucleotide sequences; information that affects the probability of distinct classes of mutation has implications for evolutionary theory.
Gain new insight on utilizing bacterial stress responses to better combat bacterial infection with antibiotics and improve biotechnology. • Reviews the vast number of new findings that have greatly advanced the understanding of bacterial stress responses in the past 10 years. • Explores general regulatory principles, including the latest findings from genomics studies, including new research findings on both specific and general stress responses. • Details how stress responses affect the interactions between bacteria and host cells and covers bacterial stress responses in different niches and communities, with an emphasis on extreme environments.
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.
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.
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.
Restriction enzymes are highly specific nucleases which occur ubiquitously among prokaryotic organisms, where they serve to protect bacterial cells against foreign DNA. Many different types of restriction enzymes are known, among them multi-subunit enzymes which depend on ATP or GTP hydrolysis for target site location. The best known representatives, the orthodox type II restriction endonucleases, are homodimers which recognize palindromic sequences, 4 to 8 base pairs in length, and cleave the DNA within or immediately adjacent to the recognition site. In addition to their important biological role (up to 10 % of the genomes of prokaryotic organisms code for restriction/modification systems!), they are among the most important enzymes used for the analysis and recombination of DNA. In addition, they are model systems for the study of protein-nucleic acids interactions and, because of their ubiquitous occurence, also for the understanding of the mechanisms of evolution.
