Download or read book Termination of Replication Stress Signaling in Saccharomyces Cerevisiae written by Carolyn Marie Jablonowski and published by . This book was released on 2016 with total page 219 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Investigating the Cellular Response to DNA Damaging Agents Through High Resolution Phenotyping in Saccharomyces Cerevisiae written by Nikko Paulo Torres and published by . This book was released on 2017 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: Genome maintenance is paramount for cell viability. Cells have at their disposal an intricate and versatile set of pathways that repair DNA damage and maintain genome integrity during DNA replication stress. In this thesis I challenge the robustness of these stress response and repair pathways using pairwise drug combinations. I found that synergy is rare and that cells are able to respond to DNA damaging agents with different modes of action. Moreover, synergy was generally reduced when drugs were applied sequentially, supporting the notion that an initial dose of DNA damage primes cells for another. I then investigated the robustness of genome maintenance pathways from the perspective of the proteins that carry out repair and stress response functions. By determining the kinetics of replication stress-induced protein relocalizations previously observed (Tkach et al., 2012), I found that proteins of similar function moved with similar timing, and that relocalization timing is unique for distinct forms of replication stress. A subset of protein relocalizations is regulated by the canonical replication stress signaling cascade. Together, these findings support the notion that robustness of genome maintenance pathways stem from their multifaceted regulation. Finally, I highlight a novel function of the replication stress effector kinase Rad53 in controlling a transcriptional program by regulating Rpn4 localization.
Download or read book Genetic and Biochemical Determinants of Replication Stress Tolerance in Saccharomyces Cerevisiae written by Robert Norman Woolstencroft and published by . This book was released on 2006 with total page 560 pages. Available in PDF, EPUB and Kindle. Book excerpt: My combined genetic and biochemical strategy has forged novel determinants of RNR regulation and has enhanced our comprehension of the response to replication stress. The ribonucleotide reductase (RNR) inhibitor hydroxyurea (HU) depletes cellular pools of deoxyribonucleotides (dNTPs) and causes replication stress by pausing replication fork progression and blocking DNA synthesis. Stalled or collapsed DNA replication forks can lead to DNA double strand breaks, chromosome rearrangement, and loss of genome stability. The DNA replication checkpoint responds to replication stress by slowing S-phase progression, stabilizing stalled replication forks, and increasing RNR complex activity. In the budding yeast Saccharomyces cerevisiae, checkpoint responses hinge on activation of Mec1 (mammalian ATR ortholog) and Rad53 (mammalian Chk2 ortholog) checkpoint kinases. To identify novel gene activities that contribute to tolerance of replication stress, I surveyed the 4,812 strains in the S. cerevisiae non-essential haploid gene deletion collection for hypersensitivity to HU. Strains bearing deletions in either CCR4 or CAF1/POP2, which encode components of the major cytoplasmic mRNA deadenylase complex, were amongst 49 gene deletions that confer susceptibility to replication stress. I found that Ccr4 cooperates with the Dun1 branch of the replication checkpoint, such that a ccr4Delta dun1Delta strain exhibits irreversible HU sensitivity and persistent Rad53 activation. Mutations in CRT1, which encodes the transcriptional repressor of RNR and DNA damage-induced genes, were uncovered as the major suppressors of ccr4Delta HU sensitivity. In addition, expression of RNR genes bypasses HU sensitivity of the ccr4Delta dun1Delta strain. These observations implicate coordinated regulation of Crt1 and RNR transcription via Ccr4 and Dun1 as a critical nodal point in the response to DNA replication stress. In parallel, I undertook a biochemical approach to interrogate the molecular function of Hug1, a small protein induced by DNA damage or replication stress. I found that Hug1 interacts with the small RNR proteins Rnr2 and Rnr4. Over-expression of HUG1 is lethal in combination with a dun1Delta mutation in the presence of HU; this lethal interaction requires a physical association of Hug1 with RNR subunits. I suggest a model whereby Hug1 is induced by HU and inhibits checkpoint responses via its physical interaction with RNR.
Download or read book Stress Activated Protein Kinases written by Francesc Posas and published by Springer Science & Business Media. This book was released on 2008-01-24 with total page 322 pages. Available in PDF, EPUB and Kindle. Book excerpt: In this book leading researchers in the field discuss the state-of-the-art of many aspects of SAPK signaling in various systems from yeast to mammals. These include various chapters on regulatory mechanisms as well as the contribution of the SAPK signaling pathways to processes such as gene expression, metabolism, cell cycle regulation, immune responses and tumorigenesis. Written by international experts, the book will appeal to cell biologists and biochemists.
Download or read book Control of Cell Division by Nutrients and ER Stress Signaling in Saccharomyces Cerevisiae written by Jinbai Guo and published by . This book was released on 2007 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: Cell cycle progression of Saccharomyces cerevisiae cells was monitored in continuous cultures limited for glucose or nitrogen. The G1 cell cycle phase, before initiation of DNA replication, did not exclusively expand when growth rate decreased. Especially during nitrogen limitation, non-G1 phases expanded almost as much as G1. In addition, cell size remained constant as a function of growth rate. These results contrast with current views that growth requirements are met before initiation of DNA replication, and suggest that distinct nutrient limitations differentially impinge on cell cycle progression. Therefore, multiple mechanisms are hypothesized to regulate the coordination of cell growth and cell division. Genetic interactions were identified between the dose-dependent cell-cycle regulator 2 (DCR2) phosphatase and genes involving in secretion/unfolded protein response pathway, including IRE1, through a genome-wide dominant negative genetic approach. Accumulation of unfolded proteins in the endoplasmic reticulum triggers the unfolded protein response (UPR). How the UPR is downregulated is not well understood. Inositol requirement 1 (IRE1) is an endoplasmic reticulum transmembrane UPR sensor in Saccharomyces cerevisiae. When the UPR is triggered, Ire1p is autophosphorylated, on Ser 840 and Ser 841, inducing the cytosolic endonuclease activity of Ire1p, thereby initiating the splicing and translational de-repression of HAC1 mRNA. Homologous to Atf/Creb1 (Hac1p) activates UPR transcription. We found that that Dcr2p phosphatase functionally and physically interacts with Ire1p. Overexpression of DCR2, but not of a catalytically inactive DCR2 allele, significantly delays HAC1 splicing and sensitizes cells to the UPR. Furthermore, Dcr2p physically interacts in vivo with Ire1p-S840E, S841E, which mimics phosphorylated Ire1p, and Dcr2p dephosphorylates Ire1p in vitro. Our results are consistent with de-phosphorylation of Ire1p being a mechanism for antagonizing UPR signaling.
Download or read book Yeast Genetics written by Jeffrey S. Smith and published by Humana. This book was released on 2016-09-17 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Yeast Genetics: Methods and Protocols is a collection of methods to best study and manipulate Saccharomyces cerevisiae, a truly genetic powerhouse. The simple nature of a single cell eukaryotic organism, the relative ease of manipulating its genome and the ability to interchangeably exist in both haploid and diploid states have always made it an attractive model organism. Genes can be deleted, mutated, engineered and tagged at will. Saccharomyces cerevisiae has played a major role in the elucidation of multiple conserved cellular processes including MAP kinase signaling, splicing, transcription and many others. 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, Yeast Genetics: Methods and Protocols will provide a balanced blend of classic and more modern genetic methods relevant to a wide range of research areas and should be widely used as a reference in yeast labs.
Download or read book Molecular Genetics of Recombination written by Andrés Aguilera and published by Springer Science & Business Media. This book was released on 2007-04-24 with total page 536 pages. Available in PDF, EPUB and Kindle. Book excerpt: This work offers a fascinating insight into a crucial genetic process. Recombination is, quite simply, one of the most important topics in contemporary biology. This book is a totally comprehensive treatment of the subject, summarizing all existing views on the topic and at the same time putting them into context. It provides in-depth and up-to-date analysis of the chapter topics, and has been written by international experts in the field.
Download or read book Cell Cycle Regulation written by Philipp Kaldis and published by Results and Problems in Cell Differentiation. This book was released on 2006-06-26 with total page 400 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book is a state-of-the-art summary of the latest achievements in cell cycle control research with an outlook on the effect of these findings on cancer research. The chapters are written by internationally leading experts in the field. They provide an updated view on how the cell cycle is regulated in vivo, and about the involvement of cell cycle regulators in cancer.
Download or read book DNA Replication and Human Disease written by Melvin L. DePamphilis and published by CSHL Press. This book was released on 2006 with total page 814 pages. Available in PDF, EPUB and Kindle. Book excerpt: At least 5 trillion cell divisions are required for a fertilized egg to develop into an adult human, resulting in the production of more than 20 trillion meters of DNA! And yet, with only two exceptions, the genome is replicated once and only once each time a cell divides. How is this feat accomplished? What happens when errors occur? This book addresses these questions by presenting a thorough analysis of the molecular events that govern DNA replication in eukaryotic cells. The association between genome replication and cell proliferation, disease pathogenesis, and the development of targeted therapeutics is also addressed. At least 160 proteins are involved in replicating the human genome, and at least 40 diseases are caused by aberrant DNA replication, 35 by mutations in genes required for DNA replication or repair, 7 by mutations generated during mitochondrial DNA replication, and more than 40 by DNA viruses. Consequently, a growing number of therapeutic drugs are targeted to DNA replication proteins. This authoritative volume provides a rich source of information for researchers, physicians, and teachers, and will stimulate thinking about the relevance of DNA replication to human disease.
Download or read book DNA Replication Recombination and Repair written by Fumio Hanaoka and published by Springer. This book was released on 2016-01-22 with total page 548 pages. Available in PDF, EPUB and Kindle. Book excerpt: 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.
Download or read book Yeast Stress Responses written by Stefan Hohmann and published by Springer Science & Business Media. This book was released on 2007-10-23 with total page 398 pages. Available in PDF, EPUB and Kindle. Book excerpt: Every cell has developed mechanisms to respond to changes in its environment and to adapt its growth and metabolism to unfavorable conditions. The unicellular eukaryote yeast has long proven as a particularly useful model system for the analysis of cellular stress responses, and the completion of the yeast genome sequence has only added to its power This volume comprehensively reviews both the basic features of the yeast genral stress response and the specific adapations to different stress types (nutrient depletion, osmotic and heat shock as well as salt and oxidative stress). It includes the latest findings in the field and discusses the implications for the analysis of stress response mechanisms in higher eukaryotes as well.
Download or read book DNA Replication Controls Volume 2 written by Eishi Noguchi and published by MDPI. This book was released on 2018-04-27 with total page 355 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book is a printed edition of the Special Issue "DNA Replication Controls" that was published in Genes
Download or read book The Mechanisms of DNA Replication written by David Stuart and published by BoD – Books on Demand. This book was released on 2013-02-20 with total page 502 pages. Available in PDF, EPUB and Kindle. Book excerpt: DNA replication is a fundamental part of the life cycle of all organisms. Not surprisingly many aspects of this process display profound conservation across organisms in all domains of life. The chapters in this volume outline and review the current state of knowledge on several key aspects of the DNA replication process. This is a critical process in both normal growth and development and in relation to a broad variety of pathological conditions including cancer. The reader will be provided with new insights into the initiation, regulation, and progression of DNA replication as well as a collection of thought provoking questions and summaries to direct future investigations.
Download or read book The Molecular Biology of the Yeast Saccharomyces Life Cycle and Inheritance written by Jeffrey N. Strathern and published by . This book was released on 1981 with total page 776 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book DNA Replication written by Hisao Masai and published by Springer. This book was released on 2018-01-22 with total page 581 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book reviews the latest trends and future directions of DNA replication research. The contents reflect upon the principles that have been established through the genetic and enzymatic studies of bacterial, viral, and cellular replication during the past decades. The book begins with a historical overview of the studies on eukaryotic DNA replication by Professor Thomas Kelly, a pioneer of the field. The following chapters include genome-wide studies of replication origins and initiation factor binding, as well as the timing of DNA replications, mechanisms of initiation, DNA chain elongation and termination of DNA replication, the structural basis of functions of protein complexes responsible for execution of DNA replication, cell cycle-dependent regulation of DNA replication, the nature of replication stress and cells’ strategy to deal with the stress, and finally how all these phenomena are interconnected to genome instability and development of various diseases. By reviewing the existing concepts ranging from the old principles to the newest ideas, the book gives readers an opportunity to learn how the classical replication principles are now being modified and new concepts are being generated to explain how genome DNA replication is achieved with such high adaptability and plasticity. With the development of new methods including cryoelectron microscopy analyses of huge protein complexes, single molecular analyses of initiation and elongation of DNA replication, and total reconstitution of eukaryotic DNA replication with purified factors, the field is enjoying one of its most exciting moments, and this highly timely book conveys that excitement to all interested readers.
Download or read book The Molecular Biology of Schizosaccharomyces pombe written by Richard Egel and published by Springer Science & Business Media. This book was released on 2013-03-14 with total page 464 pages. Available in PDF, EPUB and Kindle. Book excerpt: The fission yeast Schizosaccharomyces pombe is the favoured tool of many productive research groups throughout the world, serving as a useful model for fundamental principles and mechanisms, such as genome organization, differential gene regulation, cell-cycle control, signal transduction, or cellular morphogenesis. This book collates the current state of knowledge derived from molecular studies in this simple eukaryotic microorganism. The entire sequence of its genome has been completed, emphasizing the comparative value and model status of this yeast. The individual chapters, highlighting up-to-date views on prominent aspects of molecular organization, were written by active research scientists, presenting the results of their investigations to other workers in neighbouring fields. This book intends to serve the fission yeast community as a handy source of reference for years to come. It will also be of particular value to the ever-increasing number of researchers starting to look into fission yeast affairs for comparative reasons from other platforms of molecular genetics and cell biology.
Download or read book DNA Replication written by Sonya Vengrova and published by Humana. This book was released on 2016-10-29 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Updated and revised, this thorough volume covers a range of methods focusing on systems, including mammalian, yeast, bacterial and archaeal. This second edition of DNA Replication: Methods and Protocols describes approaches to analyze whole genomes to single molecules, as well as both in vivo and in vitro experiments. As a volume in the highly successful Methods in Molecular Biology series, chapters contain introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible protocols and tips on troubleshooting and avoiding known pitfalls. Authoritative and cutting-edge, DNA Replication: Methods and Protocols, Second Edition provides a collections of methods intended for newcomers to this research field and for established laboratories.
