Download or read book Structural Analysis of DNA Replication Across Unstable Repetitive Sequences written by Cindy Follonier and published by . This book was released on 2012 with total page 117 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 Repetitive DNA Sequences written by Andrew G. Clark and published by MDPI. This book was released on 2020-03-05 with total page 206 pages. Available in PDF, EPUB and Kindle. Book excerpt: Repetitive DNA is ubiquitous in eukaryotic genomes, and, in many species, comprises the bulk of the genome. Repeats include transposable elements that can self-mobilize and disperse around the genome, and tandemly-repeated satellite DNAs that increase in copy number due to replication slippage and unequal crossing over. Despite their abundance, repetitive DNA is often ignored in genomic studies due to technical challenges in their identification, assembly, and quantification. New technologies and methods are now providing the unprecedented power to analyze repetitive DNAs across diverse taxa. Repetitive DNA is of particular interest because it can represent distinct modes of genome evolution. Some repetitive DNA forms essential genome structures, such as telomeres and centromeres, which are required for proper chromosome maintenance and segregation, whereas others form piRNA clusters that regulate transposable elements; thus, these elements are expected to evolve under purifying selection. In contrast, other repeats evolve selfishly and produce genetic conflicts with their host species that drive adaptive evolution of host defense systems. However, the majority of repeats likely accumulate in eukaryotes in the absence of selection due to mechanisms of transposition and unequal crossing over. Even these neutral repeats may indirectly influence genome evolution as they reach high abundance. In this Special Issue, the contributing authors explore these questions from a range of perspectives.

Download or read book Genetic Instabilities and Neurological Diseases written by Robert D. Wells and published by Elsevier. This book was released on 2011-10-13 with total page 783 pages. Available in PDF, EPUB and Kindle. Book excerpt: Genetic Instabilities and Neurological Diseases covers DNA repeat instability and neurological disorders, covering molecular mechanisms of repeat expansion, pathogenic mechanisms, clinical phenotype, parental gender effects, genotype-phenotype correlation, and diagnostic applications of the molecular data. This updated edition provides updates of these repeat expansion mutations, including the addition of many new chapters, and old chapters rewritten as extensions of the previous edition. This book is an invaluable reference source for neuroscientists, geneticists, neurologists, molecular biologists, genetic counsellors and students. - Contributions by most of the principal research teams in the area, edited by world-renowned leaders - Lays the background for future investigations on related diseases

Download or read book DNA Replication Stress written by Robert M. Brosh Jr. and published by MDPI. This book was released on 2019-08-27 with total page 368 pages. Available in PDF, EPUB and Kindle. Book excerpt: This Special Issue of International Journal of Molecular Sciences (IJMS) is dedicated to the mechanisms mediated at the molecular and cellular levels in response to adverse genomic perturbations and DNA replication stress. The relevant proteins and processes play paramount roles in nucleic acid transactions to maintain genomic stability and cellular homeostasis. A total of 18 articles are presented which encompass a broad range of highly relevant topics in genome biology. These include replication fork dynamics, DNA repair processes, DNA damage signaling and cell cycle control, cancer biology, epigenetics, cellular senescence, neurodegeneration, and aging. As Guest Editor for this IJMS

Download or read book The Roles and Regulation of Specialized DNA Polymerases in Mitigating Replication Stress and Replicating Common Fragile Sites written by Ryan Barnes and published by . This book was released on 2017 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: Replicative DNA polymerases serve as the essential enzymes that duplicate our genome with high fidelity and efficiency. This function is compromised however, when repetitive DNA sequences adopt a structure differing from the Watson-Crick B-form or during conditions of replicative stress. However, cells also possess specialized DNA polymerases that can compensate for the replicative polymerases when they are inhibited. The goals of this thesis were to investigate how the specialized DNA polymerases (Pols) eta () and kappa () 1) cooperate with the replicative polymerase delta () in the synthesis of repetitive DNA derived from chromosomal fragile sites, and 2) understand how these enzymes function during cellular replication stress. Common fragile sites (CFSs) are genomic loci that display recurrent instability in cells experiencing replication stress. Replication stress, defined as the slowing or stalling of replication forks, occurs when cells are treated with agents that inhibit DNA synthesis or are deficient in DNA repair/replication enzymes. CFSs are sensitive to replication stress, and one rationale for this is their enrichment in repetitive DNA sequences that can adopt a non-B DNA structure. Previous work in the Eckert lab has shown that all three replicative, human DNA polymerases are inhibited by repetitive CFS sequences in vitro whereas polymerases and can replicate the same sequences with high efficiency. In chapter 3, I test the hypothesis that Pols and can cooperate with Pol in CFS sequence replication in vitro. To investigate this, I developed a model of lagging strand synthesis using primed ssDNA templates containing RFC-loaded PCNA, the processivity factor of Pol . This system was designed to allow RFC and Pols , , and to function optimally in the same reaction conditions. Using this system, I found that Pols and can indeed rescue the Pol holoenzyme (Pol / RFC-loaded PCNA; Pol HE) stalled at CFS sequences containing different repetitive DNA motifs. I found this polymerase cooperativity was not mediated by PCNA however, as reactions where RFC was omitted displayed no defect in replication rescue. Moreover, using this system I did not observe any enhancement of cooperativity between Pol and Pols and using mono-ubiquitinated PCNA (Ub-PCNA), a post-translational modification thought to regulate polymerase exchange at DNA lesions. Finally, by modeling replication stress in vitro using Aph, a drug that directly inhibits replicative polymerases, I found that Pols and become indispensable for repetitive CFS sequence replication. In total, the data in this chapter advances our understanding of human DNA polymerase exchange, and how repetitive DNA replication is accomplished by multiple polymerases. While the relationship between CFS stability and Pol has been characterized by work in the Eckert lab and others, we did not know how Pol might impact the cell cycle and checkpoint signaling in replication stressed cells. To study this, I employed several models of cellular Pol deficiency and uncovered a role for Pol in G2/M phase progression during replication stress. Pol -deficient cells also display increased replication checkpoint signaling during replication stress. Interestingly, this checkpoint signaling can be suppressed in cells expressing a wild-type POLH gene, as well as a POLH gene mutated at the PCNA interaction motif, but not in cells expressing a POLH gene mutated at the ubiquitin binding domain. Moreover, analysis of Pol -deficient cells recovering from replication stress revealed a persistence of replication defects and apoptosis up to 24 hours after treatment, concomitant with reduced colony formation. This chapter reveals a global role for Pol in proper cell cycle progression during and following replication stress. After uncovering these cellular phenotypes, I began a study of Y-family polymerase expression during replication stress. In Chapter 5, I present my results showing that POLH transcript and Pol protein levels significantly increase in numerous normal and transformed cell lines using two models of replication stress. Interestingly, this induction of Pol was independent of p53 status, which has been shown to regulate Pol levels. In addition, I also observed stabilization of exogenous Pol protein and increased ubiquitination of Pol during replication stress. Among the related Y family polymerases, Pol displayed no significant induction following replication stress, and while POLK mRNA did not increase, Pol protein did increase with Aph treatment. Finally, I discovered that Pol relocalizes to chromatin and forms nuclear foci during replication stress, independent of Rad18, the primary E3 ligase of PCNA. To understand what protein/pathway may be regulating Pol during replication stress, I focused on the checkpoint kinase ATR. In this chapter I detail my results showing cell-type specific regulation of Pol by ATR during replication stress, at the level of protein expression and ubiquitination. Moreover, I show that ATR protects Pol -deficient cells from apoptotic signaling during replication stress, thereby increasing their viability. Consistent with this, Pol -deficient cells depleted of ATR had a dramatic reduction in survival in comparison to ATR-proficient cells. In total, the data presented in this chapter greatly advance our understanding of Y-family polymerase regulation outside the context of DNA damage. This data in combination with Chapter 4 demonstrably shows Y-family polymerases are an integral component of the replication stress response. In the Appendix I present my studies on A/T repeat mutagenesis. CFSs are enriched in A/T repeats, and non-B DNA structures formed by these sequences are proposed to induce CFS instability. I developed several new ex vivo reporter assays to examine mutagenesis during replication of A/T repeat rich, CFS derived sequences in human cells. Here I also detail my studies of the most recently identified DNA polymerase/primase, PrimPol. Using the Eckert labs established in vitro HSV-tk mutagenesis assay, I demonstrated for the first time that PrimPol is a highly error-prone DNA polymerase, and has a unique error signature on random, B-DNA. However, PrimPols error signature on the A/T repeats is similar to Pol s, suggesting a conserved mode of repeat replication.The work presented in this thesis advances our understanding of the roles specialized DNA polymerases have in human cells, and how these enzymes are orchestrated in the face of replication stress. Taking these results together, the findings of this thesis are biologically significant because I have elucidated the mechanism underlying the fragile chromosome phenotype of Pol -deficient cells. By generating the optimal DNA template, Pol has an essential role in completing genome duplication at difficult-to-replicate sequences and traversing the mitotic checkpoint, ensuring that cells properly enter the next cell cycle after replication stress release. The human genome is characterized by its DNA sequence complexity and high repetitive DNA content, and the presence of repetitive sequences directly impacts genome stability. I provide here a new conceptual framework, wherein specialized DNA polymerases of varied biochemical properties are essential for complete duplication of highly complex genomes, functioning in each cell division.

Download or read book Repetitive DNA written by Manuel A. Garrido-Ramos and published by Karger Medical and Scientific Publishers. This book was released on 2012 with total page 239 pages. Available in PDF, EPUB and Kindle. Book excerpt: The experimental data that have been generated using new molecular techniques associated with the completion of genome projects have changed our perception of the structural features, functional implications and evolutionary dynamics of repetitive DNA sequences. This volume of Genome Dynamics provides a valuable update on recent developments in research into multigene families, centromeres, telomeres, microsatellite DNA, satellite DNA, and transposable elements. Each chapter presents a review by distinguished experts and analyzes repetitive DNA diversity and abundance, as well as the impact on genome structure, function and evolution. This publication is targeted at scientists and scholars at every level, from students to faculty members, and, indeed, anyone involved or interested in genetics, molecular evolution, molecular biology as well as genomics will find it a valuable source of up-to-date information.

Download or read book DNA Replication written by Herve Seligmann and published by BoD – Books on Demand. This book was released on 2011-08-01 with total page 712 pages. Available in PDF, EPUB and Kindle. Book excerpt: The study of DNA advanced human knowledge in a way comparable to the major theories in physics, surpassed only by discoveries such as fire or the number zero. However, it also created conceptual shortcuts, beliefs and misunderstandings that obscure the natural phenomena, hindering its better understanding. The deep conviction that no human knowledge is perfect, but only perfectible, should function as a fair safeguard against scientific dogmatism and enable open discussion. With this aim, this book will offer to its readers 30 chapters on current trends in the field of DNA replication. As several contributions in this book show, the study of DNA will continue for a while to be a leading front of scientific activities.

Download or read book DNA Damage and Chromosomal Instability written by and published by Elsevier. This book was released on 2024-02-13 with total page 350 pages. Available in PDF, EPUB and Kindle. Book excerpt: DNA Damage and Chromosomal Instability, Volume 182 in the Methods in Cell Biology series, presents interesting chapters on a variety of timely topics, including Induction of chromosome-specific micronuclei and chromothripsis by centromere inactivation, Generation of aneuploid cells and assessment of their ability to survive in presence of chemotherapeutic agents, Genetic reporters to detect and quantify homologous recombination in yeast, Mapping histone variant genomic distribution: exploiting SNAP- Tag labelling to follow the dynamics of incorporation of H3 variants, Enrichment of DNA replication intermediates by EdU pull down, Nascent DNA sequencing and its diverse applications in genome integrity research, and much more. Additional chapters cover Enrichment of DNA replication intermediates by EdU pull down, DNA curtains for studying phase separation mechanisms of DNA-organizing proteins, Visualizing the Dynamics of DNA Replication and Repair at the Single-Molecule Molecule Level, Cloning and Expansion of Repetitive DNA Sequences, Using an ImageJ-based script to detect replication stress and associated cell cycle exit from G2 phase by fluorescence microscopy Arne Lindqvist - Provides the authority and expertise of leading contributors from an international board of authors - Presents the latest release in the Methods in Cell Biology series - Updated release includes the latest information on the DNA Damage and Chromosomal Instability

Download or read book The Initiation of DNA Replication written by Dan S Ray and published by Elsevier. This book was released on 2012-12-02 with total page 649 pages. Available in PDF, EPUB and Kindle. Book excerpt: The Initiation of DNA Replication contains the proceedings of the 1981 ICN-UCLA Symposia on Structure and DNA-Protein Interactions of Replication Origins, held in Salt Lake City, Utah on March 8-13, 1981. The papers explore the initiation of DNA replication and address relevant topics such as whether there are specific protein recognition sites within an origin; how many proteins interact at an origin and whether they interact in a specific temporal sequence; or whether origins can be subdivided into distinct functional domains. The specific biochemical steps in DNA chain initiation and how they are catalyzed are also discussed. This book is organized into six sections and comprised of 41 chapters. The discussion begins by analyzing the replication origin region of the Escherichia coli chromosome and the precise location of the region carrying autonomous replicating function. A genetic map of the replication and incompatibility regions of the resistance plasmids R100 and R1 is described, and several gene products produced in vivo or in vitro from the replication region are considered. The sections that follow focus on the DNA initiation determinants of bacteriophage M13 and of chimeric derivatives carrying foreign replication determinants; suppressor loci in E. coli; and enzymes and proteins involved in initiation of phage and bacterial chromosomes. The final chapters examine the origins of eukaryotic replication. This book will be of interest to scientists, students, and researchers in fields ranging from microbiology and molecular biology to biochemistry, molecular genetics, and physiology.

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 Molecular Biology of the Cell written by and published by . This book was released on 2002 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Links Between Recombination and Replication written by Proceedings of the National Academy of Sciences and published by National Academies Press. This book was released on 2002-09-18 with total page 303 pages. Available in PDF, EPUB and Kindle. Book excerpt: There has been a sea change in how we view genetic recombination. When germ cells are produced in higher organisms, genetic recombination assures the proper segregation of like chromosomes. In the course of that process, called meiosis, recombination not only assures segregation of one chromosome of each type to progeny germ cells, but also further shuffles the genetic deck, contributing to the unique inheritance of individuals. In a nutshell, that is the classical view of recombination. We have also known for many years that in bacteria recombination plays a role in horizontal gene transfer and in replication itself, the latter by establishing some of the replication forks that are the structural scaffolds for copying DNA. In recent years, however, we have become increasingly aware that replication, which normally starts without any help from recombination, is a vulnerable process that frequently leads to broken DNA. The enzymes of recombination play a vital role in the repair of those breaks. The recombination enzymes can function via several different pathways that mediate the repair of breaks, as well as restoration of replication forks that are stalled by other kinds of damage to DNA. Thus, to the classical view of recombination as an engine of inheritance we must add the view of recombination as a vital housekeeping function that repairs breaks suffered in the course of replication. We have also known for many years that genomic instability--including mutations, chromosomal rearrangements, and aneuploidy--is a hallmark of cancer cells. Although genomic instability has many contributing causes, including faulty replication, there are many indications that recombination, faulty or not, contributes to genome instability and cancer as well. The (Nas colloquium) Links Between Recombination and Replication: Vital Roles of Recombination was convened to broaden awareness of this evolving area of research. Papers generated by this colloquium are published here. To encourage the desired interactions of specialists, we invited some contributions that deal only with recombination or replication in addition to contributions on the central thesis of functional links between recombination and replication. To aid the nonspecialist and specialist alike, we open the set of papers with a historical overview by Michael Cox and we close the set with a commentary on the meeting and the field by Andrei Kuzminov.

Download or read book Structural Analysis of DNA Sequences written by Armin Schmitt and published by . This book was released on 1995 with total page 144 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Defining Sites of Replication Fork Collapse Caused by ATR Inhibition written by Nishita K. Shastri and published by . This book was released on 2017 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Replication stress, characterized by stalling of DNA replication and the accumulation of abnormal replication intermediates, has been linked to the genomic instability observed in cancer. Previous studies have defined specific genomic sequences that are difficult to replicate to be more vulnerable to replication-associated breaks and rearrangements. However, many of these sequences have been identified through indirect and potentially biased approaches. To identify DNA sequences that contribute to replication-associated genomic instability, I will describe genome-wide screens I have performed to determine the location, sequence, and frequency of replication perturbations within the mammalian genome upon replication stress. Ataxia telangiectasia and Rad3-related protein (ATR) is a checkpoint kinase that is a key upstream regulator of the response pathway to replication fork stalling during replication stress that prevents fork collapse. Through inhibition of this response pathway in mouse embryonic fibroblasts, my aims are to 1) characterize regions that lead to frequent replication fork stalling and collapse, and 2) further define genomic regions that become processed into double-strand breaks. Since replication protein A (RPA) binds to single-stranded DNA that becomes exposed when replication forks stall, RPA ChIP-Seq has been performed to map sites of frequently collapsed replication forks; however, not all stalled replication forks result in breaks. To differentiate a replication fork that has simply stalled from a fork that has become sensitized to double-strand break formation, I developed and applied a novel and specific break-detection assay, BrITL. With these complementary approaches to map replication-problematic loci, subsequent bioinformatics methods have been utilized to characterize features of the identified genomic regions that make it prone to fork collapse and detrimental DNA break formation when cells experience replication stress. While well-established difficult-to-replicate sequences (e.g. triplet and telomere repeats) exhibited enhanced fork collapse in RPA ChP'd cells exposed to replication stress, these sequences were overshadowed by sites composed of previously uncharacterized simple tandem repeats. Circular dichroism and thermal difference absorption spectra indicate that the most commonly observed simple repeat at RPA-enriched sites (CAGAGG) folds into a stable intramolecular secondary structure and is sufficient to stall DNA replication in vitro and in vivo. BrITL analysis confirmed that these repetitive regions of RPA accumulation are also sites of DNA breakage. Interestingly, a majority of break sites identified by BrITL do not associate with RPA accumulation, but rather tend to locate around inverted retroelements that are predicted to form highly stable intrastrand stem-loop structures. Due to the lack of available ssDNA at these potential hairpin-forming sites, RPA accumulation would be limited. Overall, my studies represent the first unbiased identification of mammalian genomic sites that are vulnerable to replication stress and rely on ATR for stability.

Download or read book The Biology of Pseudomonas written by J Sokatch and published by Elsevier. This book was released on 2012-12-02 with total page 632 pages. Available in PDF, EPUB and Kindle. Book excerpt: The Bacteria, A Treatise on Structure and Function, Volume X: The Biology of Pseudomonas is generally an update of information already published about pseudomonas. This book contains information that has been discovered since the release of "Genetics and Biochemistry of Pseudomonas. Divided into three parts, the book starts with the foundation, which is the biology of the pseudomonas. The next part deals about the genetics, while the last part tackles the biochemistry of pseudomonas. The first section of this book covers topics including the modern review of the taxonomy of pseudomonas. Other sections include chapters on the important medical applications of features of these bacteria. Chapters on the virulence factors, membrane transport, and plasmids are also presented in this book. The second section of this book deals with genetics and topics including cloning and regulation of transcription. The metabolic versatility is given recognition in the third section of this book. Moreover, this section thoroughly discusses amino acid metabolism, cytochrome, and hydrocarbon catabolism.

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.