Download or read book Helicase and DNA Replication Activities of SV40 Large T Antigen written by Kyungok Wun-Kim and published by . This book was released on 1992 with total page 236 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book SV40 Large T Antigen Helicase written by and published by . This book was released on 2009 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: To initiate DNA replication, SV40 large T antigen needs to recognize and bind to the origin in SV40 DNA. This is achieved through sequence specific contacts between the T antigen origin binding domain (OBD) and the pentanucleotide regions in the center of the origin, as well as non-sequence specific interactions between the helicase domain and the EP and AT regions of the origin. This leads to the assembly of a double hexamer of T antigen over a melted origin DNA. Subsequently, the DNA becomes unwound bidirectionally, providing SS DNA templates for DNA replication. However, these events are not fully understood. For instance, it is not clear how T antigen separates DS DNA at the origin or how the separated strands become threaded through the double hexamer. In this dissertation, I identified a new unwinding activity of large T antigen. The helicase can unwind the central pentanucleotides in an ATP-hydrolysis dependent way. This activity of T antigen, like its structural distortion activity that acts on the flanking EP and AT regions, is an indispensable component of the unwinding of the entire origin. Specific sequences in the pentanucleotide region are necessary for the activity, and the flanking AT track can stimulate it. The SV40 hexameric helicase consists of a positively charged central channel and six hydrophilic channels in the large tiers. The hydrophilic channels separate adjacent large tier domains within each hexamer. In this dissertation, I generated a series of mutants with single-point substitutions in the hydrophilic channels and studied the function of the hydrophilic channels in SV40 DNA replication. The mutants were characterized in various biochemical assays and grouped into four major classes according to their properties. One class of mutant proteins (class A-D429A, N449S and N515S) displayed normal DNA binding, ATPase, and helicase activities. However, they were defective specifically at unwinding origin DNA. The three mutants were found to be deficient in EP melting activity. Two of them (D429A and N515S) also failed to unwind the central pentanucleotide region of the origin. Taken together, my data indicate that the hydrophilic channels play active roles in unwinding the origin to provide the single-stranded substrates for DNA replication. Based on my results and on published structural and functional information, a model is proposed in this dissertation to illustrate how T antigen could separate the pentanucleotide region at the center of the origin. My data also suggest a mechanism by which the step-wise assembly of the T antigen double hexamer could trigger unwinding of the origin.
Download or read book Initiation of Simian Virus 40 SV40 DNA Replication written by and published by . This book was released on 2005 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: It is well established that during initiation of SV40 DNA synthesis, a double hexamer of T antigen forms over the origin and acts as a bidirectional helicase. The subsequent events are much less clear. In fact, the structure on which DNA synthesis begins is not known, but has been hypothesized to be the double hexamer tightly associated with cellular initiation factors replication protein A (RPA), topoisomerase I (topo I) and more loosely with DNA polymerase & alpha;/primase (pol/prim). I now demonstrate that after a double hexamer forms over small origin fragments, a new structure consisting of a single hexamer associated with DNA is generated in an ATP dependent reaction from double hexamers. This structure, called the preinitiation complex (PIC), requires about 5 minutes to form whereas double hexamers are generated within 20 seconds. Importantly, PICs can associate with RPA and topo I whereas double hexamers, which have not been converted to PICs, can only bind to topo I. PICs are not simply T antigen hexamers associated with single-stranded DNA as the latter structures were shown not to bind RPA or topo I. Topo I can bind to an RPA-associated PIC, but RPA cannot bind to a topo I-associated PIC suggesting that the binding order is RPA then topo I. Importantly, DNA synthesis activity appears to be associated with the PICs but not with double hexamers. In this dissertation, a series of mutants with single-point substitutions in the helicase domain are generated to discover activities required for initiation of DNA replication. Four of these mutants (456 RA, 460ED, 462GA, and 499DA) are normal in their ability to hydrolyze ATP and are capable of associating into double hexamers in the presence of origin DNA. Furthermore, they possess normal ability to bind to single-stranded DNA. However, they fail to melt the early palindrome region of the origin. They also are severely impaired in unwinding origin-containing DNA fragments and in carrying out a helicase reaction with an M13 partial duplex DNA substrate. Interestingly, these mutants retain some ability to perform a helicase reaction with artificial replication forks, indicating that their intrinsic helicase activity is functional. Intriguingly, these mutants have almost completely lost their ability to bind to double-stranded DNA nonspecifically. Taken together, my data indicate that structural distortion and subsequent unwinding of the origin depend upon T antigen's ability to bind to DNA nonspecifically.
Download or read book Viruses and Human Disease written by Ellen G. Strauss and published by Elsevier. This book was released on 2007-09-21 with total page 476 pages. Available in PDF, EPUB and Kindle. Book excerpt: Completely revised and updated, the new edition of this groundbreaking text integrates basic virology with pathophysiological conditions to examine the connection between virology and human disease. Most virology textbooks focus on the molecular biology involved without adequate reference to physiology. This text focuses on viruses that infect humans, domestic animals and vertebrates and is based on extensive course notes from James Strauss' virology class at the California Institute of Technology taught for over 30 years. Expertly depicting in color the molecular structure and replication of each virus, it provides an excellent overview for students and professionals interested in viruses as agents of human disease. - Includes over 30% new material - virtually all of the figures and tables have been redrawn to include the latest information and the text has been extensively rewritten to include the most up-to-date information - Includes a new chapter on emerging and reemerging viral diseases such as avian flu, SARS, the spread of West Nile virus across America, and the continuing spread of Nipah virus in Southeast Asia - Further reading sections at the end of each chapter make it easy find key references - World maps depicting the current distribution of existing and newly emerging viruses are also incorporated into the text
Download or read book The SV40 Replicon Model for Analysis of Anticancer Drugs written by Robert M. Snapka and published by Elsevier. This book was released on 1996-05-23 with total page 205 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book provides the most up-to-date review of the simian virus 40 (SV40) minichromosome as a model for the mammalian chromosome in studies of DNA replication. It focuses on disruption of DNA replication by anticancer drugs and DNA-damaging agents. There is a strong emphasis on the unique advantages of SV40 as an experimental system for the analysis of these classes of anticancer drug mechanisms. The new high-resolution gel electrophoresis methods for the analysis of SV40 DNA replication are covered in detail to aid readers in designing and interpreting similar experiments. - Presents unique advantages of SV40 as an experimental system for the study of classes of anticancer drugs - Details new high-resolution gel electrophoresis methods for the analysis of SV40 DNA replication - Provides details to help the reader design and interpret similar experiments
Download or read book Modulation of the DNA Binding Activity of SV40 Large T Antigen by Cellular Protein Phosphatase 2AcC Replication Protein C written by Alicia Alexandra Rose Russo and published by . This book was released on 1989 with total page 57 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Analysis of Replication Activity of SV40 T Antigens written by Melinda Larsen and published by . This book was released on 1993 with total page 60 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Mutational Analysis of the Central Channel in the Simian Virus 40 Large T Antigen Helicase written by David Manna and published by . This book was released on 2006 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: I report in this dissertation that residues lining the small tier of the central channel have an important role in DNA binding, especially in single-stranded DNA binding. Defects in helicase activity for the small tier channel mutants can be accounted by their corresponding defects in DNA binding. One of the large tier central channel mutants (R456A) showed a defect in unwinding of origin DNA, but this could not be attributed to a problem in DNA binding. Combined with the results of others, it appears that the large tier is primarily involved in unwinding origin DNA. These findings are incorporated into a model of T antigen helicase activity where single-stranded DNA is looped out of one hexamer through hydrophilic side-channels in the large tier of the hexamer. The looped-out single-stranded DNA runs back into the origin binding domain of the adjacent hexamer. In this model, there is one strand of DNA within each small tier during DNA unwinding from the origin. (Abstract shortened by UMI.).
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.
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.
Download or read book Molecular Mechanisms in DNA Replication and Recombination written by Charles C. Richardson and published by Wiely-Liss. This book was released on 1990 with total page 448 pages. Available in PDF, EPUB and Kindle. Book excerpt: "DNA to DNA transitions are spectacular events involving phenomenal biochemical and topological complexity and astounding requisites for precision and control. Molecular Mechanisms in DNA Replication and Recombination offers a detailed understanding of the molecular mechanisms of DNA replication and recombination and their regulation. The book represents a thorough picture of the various topological forms that the DNA double helix can assume, and the way in which these forms can recognize and interact with their cognate bindings proteins and enzymes. This volume features the work of X-ray crystallographers, structural chemists, and nucleic acid enzymologists to promote the cross-fertilization of ideas, experimental approaches, and techniques. It assesses major advances in the field such as: the ways in which replication od duplex DNA genomes, both prokaryotic and eukaryotic are initiated, the replication potential of SV40 (the state of phosphorylation of large T antigen and presumably its host cell analogue) and ori C (the functional interaction of the DNA protein with phospholipids, and presumably the cell membrane), the structure and dynamics of DNA polymerase action, and the molecular mechanism of site specific and homologous recombination. Molecular Mechanisms in DNA Replication and Recombination is of importance to scientists involved in nucleic acid research, molecular biology, enzymology, and celluar biochemistry." --
Download or read book The DNA Replication Machinery as Therapeutic Targets written by Andrew F. Gardner and published by Frontiers Media SA. This book was released on 2019-09-19 with total page 144 pages. Available in PDF, EPUB and Kindle. Book excerpt: In all organisms, the DNA replication machinery is responsible for accurate and efficient duplication of the chromosome. Inhibitors of replication proteins are commonly used in anti-cancer and anti-viral therapies. This eBook on “The DNA Replication Machinery as Therapeutic Targets” examines the normal functions of replication proteins as well as strategies to target each step during the replication process including DNA unwinding, DNA synthesis, and DNA damage bypass and repair. Articles discuss current strategies to develop drugs targeting DNA replication proteins as well as future outlooks and needs.
Download or read book DNA Replication The Regulatory Mechanisms written by Patrick Hughes and published by Springer Science & Business Media. This book was released on 2012-12-06 with total page 429 pages. Available in PDF, EPUB and Kindle. Book excerpt: DNA replication is a key event in the cell cycle. Although our knowledge is far from complete and many elusive regulatory mechanisms still remain beyondour grasp, many enzymes and a multiplicity of biochemical mechanisms involved have been discovered. Recent findings in E. coli have confirmed and yet surpassed the original hypothesis of F. Jacob. In yeast and higher eucaryotes, the apparent redundancy in putative origins and initiators has made an estimation of the importance of each identified element difficult to access. In spite of well established methodologies - which are also described in the book - the origin identification in mammalian chromosomes is still a controversial subject. On the other hand, considerable advances have been made in our understanding of virus DNA replication and this continues to deepen and broaden our understanding of the controls of cellular DNA replication.
Download or read book Fundamental Aspects of DNA Replication written by Jelena Kusic-Tisma and published by BoD – Books on Demand. This book was released on 2011-09-26 with total page 322 pages. Available in PDF, EPUB and Kindle. Book excerpt: DNA replication, the process of copying one double stranded DNA molecule to produce two identical copies, is at the heart of cell proliferation. This book highlights new insights into the replication process in eukaryotes, from the assembly of pre-replication complex and features of DNA replication origins, through polymerization mechanisms, to propagation of epigenetic states. It also covers cell cycle control of replication initiation and includes the latest on mechanisms of replication in prokaryotes. The association between genome replication and transcription is also addressed. We hope that readers will find this book interesting, helpful and inspiring.
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 GENETIC AND BIOCHEMICAL ANALYSIS OF SV40 LARGE T ANTIGEN HOST INTERACTIONS T ANTIGEN written by DAVID CHARLES KOHRMAN and published by . This book was released on 1991 with total page 310 pages. Available in PDF, EPUB and Kindle. Book excerpt: p185 may be functionally important.
Download or read book Cellular Proteins Associated with SV40 Small T Antigen written by Yu-Chung Yang and published by . This book was released on 1981 with total page 276 pages. Available in PDF, EPUB and Kindle. Book excerpt:
