Tracking of Progressing Human DNA Polymerase Holoenzymes Reveals Distributions of DNA Lesion Bypass Activities PDF Download
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Author: Joseph Cardina
Publisher:
ISBN:
Category :
Languages : en
Pages : 0
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Book Description
In lagging strand DNA synthesis, DNA polymerase [delta] (pol [delta]) holoenzymes composed of pol [delta] and the proliferating cell nuclear antigen (PCNA) sliding clamp perform high fidelity DNA synthesis with little error. The pol [delta] holoenzyme occasionally encounters structural deformities in the native DNA sequence called DNA lesions. Upon encountering these lesions, it was previously believed that pol [delta] would stall on the DNA template at some point before the lesion launching a DNA damage tolerance (DDT) pathway to replicate the lesion and remaining DNA before allowing pol [delta] to resume its typical high fidelity DNA synthesis. Recent literature within the past 20 years or so has challenged this perspective by showing human pol [delta] can replicate various DNA lesions. These studies have questioned the role that DDT plays in lagging strand DNA synthesis upon encounter of a DNA lesion, thus providing a need for further analysis. As a result, we aimed to quantitatively characterize the encounters of pol [delta] with several biologically relevant DNA lesions at physiological conditions. Our results show that pol [delta] supports dNTP incorporation while inserting across from, extending from, and elongating past several different DNA lesions, and the exact extent of these values is dependent on the exonuclease activity of pol [delta] and the identity of the lesion itself. We also found that of the pol [delta] that dissociates upon encountering the lesion, the dissociation events are unevenly distributed around the lesion with different distributions depending on the lesion. Our findings show that lagging strand DNA synthesis is more complex than previously thought while advancing our understanding of the role of DDT in lagging strand DNA synthesis.
Author: Joseph Cardina
Publisher:
ISBN:
Category :
Languages : en
Pages : 0
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Book Description
In lagging strand DNA synthesis, DNA polymerase [delta] (pol [delta]) holoenzymes composed of pol [delta] and the proliferating cell nuclear antigen (PCNA) sliding clamp perform high fidelity DNA synthesis with little error. The pol [delta] holoenzyme occasionally encounters structural deformities in the native DNA sequence called DNA lesions. Upon encountering these lesions, it was previously believed that pol [delta] would stall on the DNA template at some point before the lesion launching a DNA damage tolerance (DDT) pathway to replicate the lesion and remaining DNA before allowing pol [delta] to resume its typical high fidelity DNA synthesis. Recent literature within the past 20 years or so has challenged this perspective by showing human pol [delta] can replicate various DNA lesions. These studies have questioned the role that DDT plays in lagging strand DNA synthesis upon encounter of a DNA lesion, thus providing a need for further analysis. As a result, we aimed to quantitatively characterize the encounters of pol [delta] with several biologically relevant DNA lesions at physiological conditions. Our results show that pol [delta] supports dNTP incorporation while inserting across from, extending from, and elongating past several different DNA lesions, and the exact extent of these values is dependent on the exonuclease activity of pol [delta] and the identity of the lesion itself. We also found that of the pol [delta] that dissociates upon encountering the lesion, the dissociation events are unevenly distributed around the lesion with different distributions depending on the lesion. Our findings show that lagging strand DNA synthesis is more complex than previously thought while advancing our understanding of the role of DDT in lagging strand DNA synthesis.
Author: Melvin DePamphilis
Publisher: Garland Science
ISBN: 1136738231
Category : Science
Languages : en
Pages : 476
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Book Description
Genome Duplication provides a comprehensive and readable overview of the underlying principles that govern genome duplication in all forms of life, from the simplest cell to the most complex multicellular organism. Using examples from the three domains of life - bacteria, archaea, and eukarya - Genome Duplication shows how all living organisms store their genome as DNA and how they all use the same evolutionary-conserved mechanism to duplicate it: semi-conservative DNA replication by the replication fork. The text shows how the replication fork determines where organisms begin genome duplication, how they produce a complete copy of their genome each time a cell divides, and how they link genome duplication to cell division. Genome Duplication explains how mistakes in genome duplication are associated with genetic disorders and cancer, and how understanding genome duplication, its regulation, and how the mechanisms differ between different forms of life, is critical to the understanding and treatment of human disease.
Author: Giovanni Maga
Publisher: World Scientific
ISBN: 9813226420
Category : Science
Languages : en
Pages : 398
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Book Description
Maintenance of the information embedded in the genomic DNA sequence is essential for life. DNA polymerases play pivotal roles in the complex processes that maintain genetic integrity. Besides their tasks in vivo, DNA polymerases are the workhorses in numerous biotechnology applications such as the polymerase chain reaction (PCR), cDNA cloning, next generation sequencing, nucleic acids based diagnostics and in techniques to analyze ancient and otherwise damaged DNA (e.g. for forensic applications). Moreover, some diseases are related to DNA polymerase defects and chemotherapy through inhibition of DNA polymerases is used to fight HIV, Herpes and Hepatitis B and C infections. This book focuses on (i) biology of DNA polymerases, (ii) medical aspects of DNA polymerases and (iii) biotechnological applications of DNA polymerases. It is intended for a wide audience from basic scientists, to diagnostic laboratories, to companies and to clinicians, who seek a better understanding and the practical use of these fascinating enzymes.
Author: Maria Spies
Publisher: Springer Science & Business Media
ISBN: 1461450373
Category : Medical
Languages : en
Pages : 308
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Book Description
In recent years, a number of groundbreaking structural and mechanistic studies deepened our understanding of helicase mechanisms and established new approaches for their analyses. Many fundamental mechanistic questions ranging from the mechanism of force generation, mechanochemical coupling to distinct mechanisms by which the same enzyme translocates on DNA removing obstacles, unwinds DNA and/or remodels nucleoprotein complexes, however, remain to be answered. It is even less understood how the helicase motors are incorporated into a wide range of genome maintenance and repair machines. The field has reached a stage when the studies of molecular mechanisms and basic biology of helicases can and shall be integrated with the studies of development, cancer and longevity. The objective of this book is to provide the first systematic overview of structure, function and regulation of DNA helicases and related molecular motors. By integrating the knowledge obtained through the diverse technical approaches ranging from single-molecule biophysics to cellular and molecular biological studies the editors aim to provide a unified view on how helicases function in the cell, are regulated in response to different cellular stresses and are integrated into large macromolecular assemblies to form a complex and adaptive living system.
Author:
Publisher: Academic Press
ISBN: 9780120342693
Category : Science
Languages : en
Pages : 368
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Book Description
DNA Repair and Replication contains an up-to-date review of general principles of DNA replication and an overview of the multiple pathways involved in DNA repair. Specific DNA repair pathways, including base-excision repair, light-dependent direct reversal of UV-damage, nucleotide-excision repair, transcription-coupled repair, double-strand break repair, and mismatch repair, are each discussed in separate chapters. Selected Contents: Base Excision Repair Eukaryotic DNA Mismatch Repair Double Strand Break Repair Functions of DNA Polymerases Somatic Hypermutation: A Mutational Panacea
Author: Robert D. Wells
Publisher: Springer
ISBN: 9781461415299
Category : Science
Languages : en
Pages : 0
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Book Description
Molecular Life Sciences: An Encyclopedic Reference will focus on understanding biological phenomena at the level of molecules and their interactions that govern life processes. The work will include articles on genes and genomes, protein structure and function, systems biology using genomics and proteomics as the focus, molecular aspects of cell structure and function, unifying concepts and theories from biology, chemistry, mathematics and physics that are essential for understanding the molecular life sciences (including teaching perspectives and assessment tools), and basic aspects of the various experimental approaches that are used in the Molecular Life Sciences.
Author: Jeffrey A Stuart
Publisher: Humana Press
ISBN: 9781934115602
Category : Science
Languages : en
Pages : 0
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Book Description
Since the publication of the first edition, the number of unique heritable mtDNA mutations recognized as being associated with bioenergetic dysfunction, cell death and disease has grown. Likewise, our understanding of the basic biology of somatic mtDNA mutations continues to improve. In Mitochondrial DNA: Methods and Protocols, Second Edition, specialists from eight countries share their expertise, providing detailed protocols for studying many aspects of mtDNA. The volume is divided into three sections, which cover the transduction of information from mtDNA to functionally active respiratory complexes, mitochondrial reactive oxygen species (ROS) production as well as mtDNA damage and its repair, and the identification and quantification of heteroplasmic mtDNA mutations. Written in the highly successful Methods in Molecular BiologyTM series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and notes sections, highlighting tips on troubleshooting and avoiding known pitfalls. Comprehensive and authoritative, Mitrochondrial DNA: Methods and Protocols, Second Edition promises to aid researchers in further expanding our knowledge of this vital area of cell biology.
Author: Roland Benz
Publisher: Wiley-VCH Verlag GmbH
ISBN: 9783527307753
Category : Eukaryotic Cells
Languages : en
Pages : 0
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Book Description
For the first time, current knowledge on this important of proteins is now available in a single resource. This first book on porins in prokaryotes and eukaryotes relates the known physiological functions of porins to their molecular structure and mechanism. It brings together biophysical evidence with studies performed in a cellular context, presenting a unified picture of the fundamental importance of porins for cellular function. From the contents: Structure of Prokaryotic Porins Functional Reconstitution of Porins Regulation of Bacterial Porin Function Role of Porins in Antibiotic Susceptibility Drug Efflux and Protein Export through Porins Structure and Function of Mitochondrial Porins VDAC Function in Intracellular Signalling and Apoptosis With 16 contributions by an interdisciplinary team of leading porin researchers, this reference is essential reading for every molecular or structural biologist with an interest in this important protein family.
Author: J. Robin Harris
Publisher: Springer Nature
ISBN: 3030589714
Category : Science
Languages : en
Pages : 580
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Book Description
This book covers important topics such as the dynamic structure and function of the 26S proteasome, the DNA replication machine: structure and dynamic function and the structural organization and protein–protein interactions in the human adenovirus capsid, to mention but a few. The 18 chapters included here, written by experts in their specific field, are at the forefront of scientific knowledge. The impressive integration of structural data from X-ray crystallography with that from cryo-electron microscopy is apparent throughout the book. In addition, functional aspects are also given a high priority. Chapter 1 is available open access under a Creative Commons Attribution 4.0 International License via link.springer.com.
Author: Moselio Schaechter
Publisher: Academic Press
ISBN: 0080961282
Category : Science
Languages : en
Pages : 1277
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Book Description
The Desk Encyclopedia of Microbiology, Second Edition is a single-volume comprehensive guide to microbiology for the advanced reader. Derived from the six volume e-only Encyclopedia of Microbiology, Third Edition, it bridges the gap between introductory texts and specialized reviews. Covering topics ranging from the basic science of microbiology to the current "hot" topics in the field, it will be invaluable for obtaining background information on a broad range of microbiological topics, preparing lectures and preparing grant applications and reports. - The most comprehensive single-volume source providing an overview of microbiology to non-specialists - Bridges the gap between introductory texts and specialized reviews - Provides concise and general overviews of important topics within the field making it a helpful resource when preparing for lectures, writing reports, or drafting grant applications
