The Roles Of The Helicase Double Hexamer Complex And The Ssdna Binding Protein Rpa During Eukaryotic Dna Replication

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The Roles of the Helicase Double-hexamer Complex and the SsDNA-binding Protein RPA During Eukaryotic DNA Replication

Author : Caitlin Marie Niesen Friend
Publisher :
ISBN 13 :
Total Pages : 163 pages
Book Rating : 4.:/5 (119 download)

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Book Synopsis The Roles of the Helicase Double-hexamer Complex and the SsDNA-binding Protein RPA During Eukaryotic DNA Replication by : Caitlin Marie Niesen Friend

Download or read book The Roles of the Helicase Double-hexamer Complex and the SsDNA-binding Protein RPA During Eukaryotic DNA Replication written by Caitlin Marie Niesen Friend and published by . This book was released on 2020 with total page 163 pages. Available in PDF, EPUB and Kindle. Book excerpt: Eukaryotic DNA replication is a complex process that must occur accurately, completely, and only once per cell cycle. To accomplish these goals, the events of DNA replication are tightly coupled to cell-cycle progression. Origins of replication are licensed by loading of the Mcm2-7 replicative DNA helicase during G1. Two Mcm2-7 hexamers load onto each origin as a double hexamer encircling dsDNA. At this stage, the helicases are inactive. Upon entry into S phase, loaded Mcm2-7 complexes then recruit a number of other replication proteins that activate the helicase. Helicase activation results in separation of the double hexamer, a transition to encircling ssDNA, and initiation of DNA unwinding. Once activated, the helicase produces the ssDNA that acts as template for new DNA synthesis. Helicase activation is the committed step of DNA replication after which the cell must complete genome duplication before it can segregate its chromosomes and divide. The work described in this thesis focuses on mechanisms that are essential for eukaryotic DNA replication with a focus on DNA unwinding and DNA synthesis. In Chapter II, I explore the essential functions and purpose of the double-hexamer conformation of the loaded helicases. Using a helicase mutant that loads as two single hexamers, I show that initial origin DNA melting can occur in the context of a single-hexamer helicase. Importantly, the amount of unwinding that occurs within a single helicase is not sufficient to allow the transition onto ssDNA. Further DNA unwinding and subsequent DNA synthesis requires robust double-hexamer helicase interactions. Together, my findings strongly suggest that the double-hexamer conformation is essential to complete helicase activation. In Chapter III, I explore the role and specificity of ssDNA-binding proteins (SSBs) in eukaryotic DNA replication. To this end, I substituted the eukaryotic SSB RPA with SSBs from other systems: E. coli SSB (EcSSB) and T4 bacteriophage Gp32. I find that DNA unwinding is supported by RPA and EcSSB but not Gp32, suggesting that eukaryotic DNA unwinding requires at least one SSB function beyond ssDNA binding. Although both RPA and EcSSB support DNA synthesis, we only observed robust lagging-strand synthesis in the presence of RPA. My studies indicate that RPA must perform multiple functions beyond ssDNA binding to facilitate eukaryotic DNA replication.

The Eukaryotic Replisome: a Guide to Protein Structure and Function

Author : Stuart MacNeill
Publisher : Springer Science & Business Media
ISBN 13 : 9400745729
Total Pages : 344 pages
Book Rating : 4.4/5 (7 download)

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Book Synopsis The Eukaryotic Replisome: a Guide to Protein Structure and Function by : Stuart MacNeill

Download or read book The Eukaryotic Replisome: a Guide to Protein Structure and Function written by Stuart MacNeill and published by Springer Science & Business Media. This book was released on 2012-08-23 with total page 344 pages. Available in PDF, EPUB and Kindle. Book excerpt: High-fidelity chromosomal DNA replication underpins all life on the planet. In humans, there are clear links between chromosome replication defects and genome instability, genetic disease and cancer, making a detailed understanding of the molecular mechanisms of genome duplication vital for future advances in diagnosis and treatment. Building on recent exciting advances in protein structure determination, the book will take the reader on a guided journey through the intricate molecular machinery of eukaryotic chromosome replication and provide an invaluable source of information, ideas and inspiration for all those with an interest in chromosome replication, whether from a basic science, translational biology and medical research perspective.

DNA Replication Controls: Volume 1

Author : Eishi Noguchi
Publisher : MDPI
ISBN 13 : 3038425680
Total Pages : 313 pages
Book Rating : 4.0/5 (384 download)

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Book Synopsis DNA Replication Controls: Volume 1 by : Eishi Noguchi

Download or read book DNA Replication Controls: Volume 1 written by Eishi Noguchi and published by MDPI. This book was released on 2018-04-27 with total page 313 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

DNA helicases: expression, functions and clinical implications

Author : Fumiaki Uchiumi
Publisher : Frontiers Media SA
ISBN 13 : 2889195759
Total Pages : 80 pages
Book Rating : 4.8/5 (891 download)

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Book Synopsis DNA helicases: expression, functions and clinical implications by : Fumiaki Uchiumi

Download or read book DNA helicases: expression, functions and clinical implications written by Fumiaki Uchiumi and published by Frontiers Media SA. This book was released on 2015-06-26 with total page 80 pages. Available in PDF, EPUB and Kindle. Book excerpt: Helicases are the proteins that bind to double- or single-stranded DNA and/or RNA chains to unwind higher order structures, usually consuming energy from the hydrolysis of ATP molecules. The biological roles of helicases are associated with a variety of DNA and/or RNA metabolisms, including DNA-replication, -repair, -recombination, RNA processing, and transcription. Dysfunctions of helicases cause various diseases, such as xeroderma pigmentosum (XP), premature aging syndrome, cancer and immunodeficiency, in humans. Moreover, recent genetic analyses revealed that mutations in helicase-encoding genes are frequently found in patients of specific diseases. Some helicases regulate cellular senescence by controlling integrity of genomes, and others play a role in neuromuscular functions presumably by modulating processing of mRNAs. However, the molecular mechanisms of how helicases are regulated in order to maintain our health are not yet fully understood. In this research topic, we will focus on the expression and functions of helicases and their encoding genes, reviewing recent research progresses that provide new insights into development of clinical and pharmaceutical treatments targeting helicases.

Macromolecular Protein Complexes III: Structure and Function

Author : J. Robin Harris
Publisher : Springer Nature
ISBN 13 : 3030589714
Total Pages : 580 pages
Book Rating : 4.0/5 (35 download)

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Book Synopsis Macromolecular Protein Complexes III: Structure and Function by : J. Robin Harris

Download or read book Macromolecular Protein Complexes III: Structure and Function written by J. Robin Harris and published by Springer Nature. This book was released on 2020-11-30 with total page 580 pages. Available in PDF, EPUB and Kindle. Book excerpt: 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.

DNA Repair

Author : Francesca Storici
Publisher : BoD – Books on Demand
ISBN 13 : 9533076496
Total Pages : 396 pages
Book Rating : 4.5/5 (33 download)

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Book Synopsis DNA Repair by : Francesca Storici

Download or read book DNA Repair written by Francesca Storici and published by BoD – Books on Demand. This book was released on 2011-09-09 with total page 396 pages. Available in PDF, EPUB and Kindle. Book excerpt: DNA repair is fundamental to all cell types to maintain genomic stability. A collection of cutting-edge reviews, DNA Repair - On the pathways to fixing DNA damage and errors covers major aspects of the DNA repair processes in a large variety of organisms, emphasizing foremost developments, questions to be solved and new directions in this rapidly evolving area of modern biology. Written by researchers at the vanguard of the DNA repair field, the chapters highlight the importance of the DNA repair mechanisms and their linkage to DNA replication, cell-cycle progression and DNA recombination. Major topics include: base excision repair, nucleotide excision repair, mismatch repair, double-strand break repair, with focus on specific inhibitors and key players of DNA repair such as nucleases, ubiquitin-proteasome enzymes, poly ADP-ribose polymerase and factors relevant for DNA repair in mitochondria and embryonic stem cells. This book is a journey into the cosmos of DNA repair and its frontiers.

Mechanism and Importance of Mcm2-7 Double-hexamer Formation During DNA Replication Initiation

Author : Kanokwan Champasa
Publisher :
ISBN 13 :
Total Pages : 147 pages
Book Rating : 4.:/5 (112 download)

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Book Synopsis Mechanism and Importance of Mcm2-7 Double-hexamer Formation During DNA Replication Initiation by : Kanokwan Champasa

Download or read book Mechanism and Importance of Mcm2-7 Double-hexamer Formation During DNA Replication Initiation written by Kanokwan Champasa and published by . This book was released on 2019 with total page 147 pages. Available in PDF, EPUB and Kindle. Book excerpt: All cells must duplicate their genome completely and accurately in each cell cycle. Thus, DNA replication is a highly-regulated multi-step process that ensures the genome is duplicated only once per cell cycle. In eukaryotic cells, initiation of DNA replication begins with loading of two heterohexameric Mcm2-7 helicases around origin DNA during G1 phase. The two helicases are loaded in opposite orientations and interact with each other at their N-terminal domains to form a head-to-head "double hexamer". In S phase, the helicases are activated by helicase-activation proteins to initiate DNA unwinding. Importantly, this event is the committed step of replication initiation. Loading of two helicases in the head-to-head double hexamer ensures DNA unwinding on both sides of the origin and allows the assembly of bi-directional forks essential for complete DNA replication. Two Mcm2-7 helicases are loaded onto the DNA sequentially. The order of events during the first helicase loading has been established, but the mechanism of double-hexamer formation remains unclear. Because the two helicases interact at their N-terminal domains, these regions represent potential mediators of double-hexamer formation. This thesis outlines the potential mechanism and the importance of double-hexamer formation. A conserved motif within Mcm2-7 N-terminal region is required for stable double-hexamer formation and cell viability. Single-molecule analyses of Mcm2-7 containing a mutation within this motif indicated that this mutant form double-hexamer interactions briefly before the two hexamers come apart. Interestingly, after double-hexamer dissolution, the two mutant helicases do not form subsequent double-hexamer interaction. Both wild-type and the mutant Mcm2-7 exhibit double-hexamer interaction rapidly after the arrival of the second Mcm2-7. Together, these data support the model that double-hexamer formation is coordinated with loading of the second Mcm2-7. Finally, the requirement of the double hexamer during helicase activation was investigated using Mcm2-7 complex containing the mutant that inhibits double-hexamer formation. The double hexamer is not essential for recruitment of three critical helicase-activation proteins, but it is required for initial origin DNA unwinding. These findings identify a crucial motif for stable double-hexamer formation and suggest that DNA unwinding is the first step in replication initiation that requires double-hexamer form of the helicases.

DNA Replication

Author : Hisao Masai
Publisher : Springer
ISBN 13 : 9811069557
Total Pages : 581 pages
Book Rating : 4.8/5 (11 download)

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Book Synopsis DNA Replication by : Hisao Masai

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.

Elucidating the Role of Dpb11 in Replication Initiation

Author : Nalini Dhingra
Publisher :
ISBN 13 :
Total Pages : 103 pages
Book Rating : 4.:/5 (913 download)

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Book Synopsis Elucidating the Role of Dpb11 in Replication Initiation by : Nalini Dhingra

Download or read book Elucidating the Role of Dpb11 in Replication Initiation written by Nalini Dhingra and published by . This book was released on 2015 with total page 103 pages. Available in PDF, EPUB and Kindle. Book excerpt:

The Initiation of DNA Replication in Eukaryotes

Author : Daniel L. Kaplan
Publisher : Springer
ISBN 13 : 3319246968
Total Pages : 564 pages
Book Rating : 4.3/5 (192 download)

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Book Synopsis The Initiation of DNA Replication in Eukaryotes by : Daniel L. Kaplan

Download or read book The Initiation of DNA Replication in Eukaryotes written by Daniel L. Kaplan and published by Springer. This book was released on 2016-02-11 with total page 564 pages. Available in PDF, EPUB and Kindle. Book excerpt: Every time a cell divides, a copy of its genomic DNA has to be faithfully copied to generate new genomic DNA for the daughter cells. The process of DNA replication needs to be precisely regulated to ensure that replication of the genome is complete and accurate, but that re-replication does not occur. Errors in DNA replication can lead to genome instability and cancer. The process of replication initiation is of paramount importance, because once the cell is committed to replicate DNA, it must finish this process. A great deal of progress has been made in understanding how DNA replication is initiated in eukaryotic cells in the past ten years, but this is the first one-source book on these findings. The Initiation of DNA Replication in Eukaryotes will focus on how DNA replication is initiated in eukaryotic cells. While the concept of replication initiation is simple, its elaborate regulation and integration with other cell processes results in a high level of complexity. This book will cover how the position of replication initiation is chosen, how replication initiation is integrated with the phases of the cell cycle, and how it is regulated in the case of damage to DNA. It is the cellular protein machinery that enables replication initiation to be activated and regulated. We now have an in-depth understanding of how cellular proteins work together to start DNA replication, and this new resource will reveal a mechanistic description of DNA replication initiation as well.

Encyclopedia of Biological Chemistry

Author :
Publisher : Academic Press
ISBN 13 : 0123786312
Total Pages : 3223 pages
Book Rating : 4.1/5 (237 download)

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Book Synopsis Encyclopedia of Biological Chemistry by :

Download or read book Encyclopedia of Biological Chemistry written by and published by Academic Press. This book was released on 2013-01-08 with total page 3223 pages. Available in PDF, EPUB and Kindle. Book excerpt: The 4-volume Encyclopedia of Biological Chemistry, Second Edition, represents the current state of a dynamic and crucial field of study. The Encyclopedia pulls together over 500 articles that help define and explore contemporary biochemistry, with content experts carefully chosen by the Editorial Board to assure both breadth and depth in its coverage. Editors-In-Chief William J. Lennarz and M. Daniel Lane have crafted a work that proceeds from the acknowledgement that understanding every living process-from physiology, to immunology, and genetics-is impossible without a grasp on the basic chemistry that provides its underpinning. Each article in the work provides an up-to-date snapshot of a given topic, written by experts, as well as suggestions for further readings for students and researcher wishing to go into greater depth. Available on-line via SciVerse ScienceDirect, the functionality of the Encyclopedia will provide easy linking to referenced articles, electronic searching, as well an online index and glossary to aid comprehension and searchability. This 4-volume set, thoroughly up-to-date and comprehensive, expertly captures this fast-moving field Curated by two esteemed editors-in-chief and an illustrious team of editors and contributors, representing the state of the field Suggestions for further readings offer researchers and students avenues for deeper exploration; a wide-ranging glossary aids comprehension

The Mechanisms of DNA Replication

Author : David Stuart
Publisher : BoD – Books on Demand
ISBN 13 : 953510991X
Total Pages : 502 pages
Book Rating : 4.5/5 (351 download)

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Book Synopsis The Mechanisms of DNA Replication by : David Stuart

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.

DNA Replication, Recombination, and Repair

Author : Fumio Hanaoka
Publisher : Springer
ISBN 13 : 443155873X
Total Pages : 548 pages
Book Rating : 4.4/5 (315 download)

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Book Synopsis DNA Replication, Recombination, and Repair by : Fumio Hanaoka

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.

Chromosome Biology

Author : Rudi Appels
Publisher : Springer Science & Business Media
ISBN 13 : 1461554098
Total Pages : 405 pages
Book Rating : 4.4/5 (615 download)

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Book Synopsis Chromosome Biology by : Rudi Appels

Download or read book Chromosome Biology written by Rudi Appels and published by Springer Science & Business Media. This book was released on 2012-12-06 with total page 405 pages. Available in PDF, EPUB and Kindle. Book excerpt: Chromosome biology has been brought to a golden age by phenomenal advanced in molecular genetics and techniques. This is true in the plant arena, and it is becoming increasingly true in animal studies, where chromosomes are more difficult to work with. With advanced knowledge of transformation, scientists can tell exactly where a new element enters a chromosome. Conversely, molecular biologists can make large mistakes if they do not understand the behavior of chromosomes. Written by internationally recognized experts in the field, this book is the most authoritative work on the subject to date. Students of genetics, crop science and plant breeding, entomology, animal science, and related fields will benefit from this comprehensive and practical textbook.

DNA Helicases and DNA Motor Proteins

Author : Maria Spies
Publisher : Springer Science & Business Media
ISBN 13 : 1461450373
Total Pages : 308 pages
Book Rating : 4.4/5 (614 download)

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Book Synopsis DNA Helicases and DNA Motor Proteins by : Maria Spies

Download or read book DNA Helicases and DNA Motor Proteins written by Maria Spies and published by Springer Science & Business Media. This book was released on 2012-11-19 with total page 308 pages. Available in PDF, EPUB and Kindle. Book excerpt: 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.

DNA Tumor Viruses

Author : Blossom Damania
Publisher : Springer Science & Business Media
ISBN 13 : 0387689451
Total Pages : 805 pages
Book Rating : 4.3/5 (876 download)

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Book Synopsis DNA Tumor Viruses by : Blossom Damania

Download or read book DNA Tumor Viruses written by Blossom Damania and published by Springer Science & Business Media. This book was released on 2008-12-19 with total page 805 pages. Available in PDF, EPUB and Kindle. Book excerpt: This unique book focuses on the DNA viruses in the human population that are associated with cancers. It covers most of the viruses that are thought to contribute to human malignancy. This book represents a comprehensive review of the field of DNA tumor virology. Right now, while there are books out there that cover individual viruses that are also covered in this book, there is no single book that covers this topic comprehensively. This book is the first current, comprehensive review of its kind in the market.

Genome Duplication

Author : Melvin DePamphilis
Publisher : Garland Science
ISBN 13 : 1136738231
Total Pages : 476 pages
Book Rating : 4.1/5 (367 download)

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Book Synopsis Genome Duplication by : Melvin DePamphilis

Download or read book Genome Duplication written by Melvin DePamphilis and published by Garland Science. This book was released on 2010-10-06 with total page 476 pages. Available in PDF, EPUB and Kindle. Book excerpt: 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.