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Book Mutational Analysis of the Central Channel in the Simian Virus 40 Large T Antigen Helicase

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.).

Book Mutational Analysis of the Origin Binding Domain of Simian Virus 40 Large T antigen Provides Insights Into Its Function in DNA Unwinding

Download or read book Mutational Analysis of the Origin Binding Domain of Simian Virus 40 Large T antigen Provides Insights Into Its Function in DNA Unwinding written by Erin C. Foster and published by . This book was released on 2010 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: DNA replication is an essential process of cell division required in order to maintain genomic integrity of all dividing cells. Although advancements have been made toward further understanding of this process, much is still unknown about the mechanisms underlying DNA replication, especially in mammalian systems. Eukaryotic DNA replication is a tightly regulated and complex process involving a myriad of proteins and numerous origins. Due to this complexity Simian Virus 40 (SV40) is used as a model system to simplify the investigation of the function of individual protein components. The replication of SV40 DNA employs one multifunctional viral protein, large T-antigen (T-ag). Many structural and genetic studies have provided a wealth of information about T-ag; however much remains unknown about the specific interactions between T-ag, DNA and replication factors and the precise sequence of events during replication. SV40 large T-ag is a multidomain protein that functions in origin recognition and unwinding events during initiation of SV40 DNA replication. The Origin Binding Domain (OBD) of T-ag plays a critical role during initiation to position T-ag on the origin through the use of a DNA binding motif consisting of A1 and B2 loops. After origin recognition, T-ag forms a double hexamer over the origin. Within each hexamer, the OBD adopts a lock washer structure where the origin recognizing A1 and B2 loops face towards the helicase domain and likely become unavailable for DNA binding. New surfaces of the OBD monomers are positioned along the DNA axis during hexamer formation. The role of the central channel of the OBD hexamer in DNA replication was investigated by analyzing the effects of mutations of residues lining the channel. All mutants showed binding defects with origin DNA and ssDNA especially at low protein concentrations, but only half were defective at supporting DNA replication in vitro. All mutants were normal in unwinding linear origin DNA fragments. However, replication defective mutants failed to unwind a small origin containing circular DNA whereas replication competent mutants did so normally. The presence of RPA and/or pol/prim restored circular DNA unwinding activity of compromised mutants probably by interacting with the separated DNA strands on the T-ag surface. The addition of RPA also recovered the ability of replication deficient mutants to support initiation and complete DNA replication in vitro. The addition of pol/prim resulted in the greatest recovery of mutant activity in minicircle unwinding and initiation. Compared to other polymerases tested, pol/prim was the only polymerase able to rescue mutant activity to WT levels indicated that this stimulation is specific to pol/prim. Of the four subunits of the pol/prim complex that could be responsible for stimulating mutant activity, the p180 subunit appeared to be active in recovering circular DNA unwinding. These results indicated a role for the OBD central channel in binding and threading ssDNA during unwinding of circular SV40 DNA. Mixing mutant and WT T-ag in minicircle unwinding assays suggested that only one monomer in an OBD hexamer was necessary for DNA unwinding. Results allowed for the development of a model of DNA threading through the T-ag complex illustrating how single stranded DNA could pass close to a trough generated by key residues in one monomer of the OBD hexamer.

Book SV40 Large T Antigen Helicase

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.

Book Viral Genome Replication

    Book Details:
  • Author : Craig E. Cameron
  • Publisher : Lulu.com
  • Release :
  • ISBN : 0359579507
  • Pages : 636 pages

Download or read book Viral Genome Replication written by Craig E. Cameron and published by Lulu.com. This book was released on with total page 636 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Book Viruses and Human Disease

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

Book Human Herpesviruses

    Book Details:
  • Author : Ann Arvin
  • Publisher : Cambridge University Press
  • Release : 2007-08-16
  • ISBN : 1139461648
  • Pages : 1325 pages

Download or read book Human Herpesviruses written by Ann Arvin and published by Cambridge University Press. This book was released on 2007-08-16 with total page 1325 pages. Available in PDF, EPUB and Kindle. Book excerpt: This comprehensive account of the human herpesviruses provides an encyclopedic overview of their basic virology and clinical manifestations. This group of viruses includes human simplex type 1 and 2, Epstein–Barr virus, Kaposi's Sarcoma-associated herpesvirus, cytomegalovirus, HHV6A, 6B and 7, and varicella-zoster virus. The viral diseases and cancers they cause are significant and often recurrent. Their prevalence in the developed world accounts for a major burden of disease, and as a result there is a great deal of research into the pathophysiology of infection and immunobiology. Another important area covered within this volume concerns antiviral therapy and the development of vaccines. All these aspects are covered in depth, both scientifically and in terms of clinical guidelines for patient care. The text is illustrated generously throughout and is fully referenced to the latest research and developments.

Book Chromosome Biology

    Book Details:
  • Author : Rudi Appels
  • Publisher : Springer Science & Business Media
  • Release : 2012-12-06
  • ISBN : 1461554098
  • Pages : 405 pages

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.

Book Cumulated Index Medicus

Download or read book Cumulated Index Medicus written by and published by . This book was released on 1995 with total page 1540 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Book Molecular Virology

    Book Details:
  • Author : Susanne Modrow
  • Publisher : Springer
  • Release : 2013-09-18
  • ISBN : 9783642207174
  • Pages : 0 pages

Download or read book Molecular Virology written by Susanne Modrow and published by Springer. This book was released on 2013-09-18 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: The book gives a comprehensive overview on the knowledge of virus infection relevant for humans and animals. For each virus family the molecular details of the virus particle and the viral replication cycle are described. In the case of virus types with relevance for human and/or animal health the data on molecular biology, genetics and virus-cell interaction are combined with those concerning, pathogenesis, epidemiology, clinics, prevention and therapy.

Book Oral  Head and Neck Oncology and Reconstructive Surgery   E Book

Download or read book Oral Head and Neck Oncology and Reconstructive Surgery E Book written by R. Bryan Bell and published by Elsevier Health Sciences. This book was released on 2017-08-25 with total page 967 pages. Available in PDF, EPUB and Kindle. Book excerpt: Oral, Head and Neck Oncology and Reconstructive Surgery is the first multidisciplinary text to provide readers with a system for managing adult head and neck cancers based upon stage. Using an evidence-based approach to the management and treatment of a wide variety of clinical conditions, the extensive experience of the author and contributors in head and neck surgery and oncology are highlighted throughout the text. This includes computer aided surgical simulation, intraoperative navigation, robotic surgery, endoscopic surgery, microvascular reconstructive surgery, molecular science, and tumor immunology. In addition, high quality photos and illustrations are included, which are easily accessible on mobile devices. - Management protocols and outcomes assessment provide clear guidelines for managing problems related to adult head and neck oncology and reconstructive surgery. - State-of-the art guidance by recognized experts details current techniques as well as technological advances in head and neck/cranio-maxillofacial surgery and oncology. - Evidence-based content details the latest diagnostic and therapeutic options for treating a wide-variety of clinical problems with an emphasis on surgical technique and outcomes. - Multidisciplinary approach reflects best practices in managing head and neck oncology and cranio-maxillofacial surgery. - 900 highly detailed images clearly demonstrate pathologies and procedures. - Designed for the modern classroom which lets you access important information anywhere through mobile tablets and smart phones.

Book Flexible Viruses

    Book Details:
  • Author : Vladimir Uversky
  • Publisher : John Wiley & Sons
  • Release : 2012-02-07
  • ISBN : 0470618310
  • Pages : 532 pages

Download or read book Flexible Viruses written by Vladimir Uversky and published by John Wiley & Sons. This book was released on 2012-02-07 with total page 532 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book provides up-to-date information on experimental and computational characterization of the structural and functional properties of viral proteins, which are widely involved in regulatory and signaling processes. With chapters by leading research groups, it features current information on the structural and functional roles of intrinsic disorders in viral proteomes. It systematically addresses the measles, HIV, influenza, potato virus, forest virus, bovine virus, hepatitis, and rotavirus as well as viral genomics. After analyzing the unique features of each class of viral proteins, future directions for research and disease management are presented.

Book Protein Nucleic Acid Interactions

Download or read book Protein Nucleic Acid Interactions written by Phoebe A. Rice and published by Royal Society of Chemistry. This book was released on 2008-05-22 with total page 417 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book provides both in-depth background and up-to-date information in this area. The chapters are organized by general themes and principles, written by experts who illustrate topics with current findings. Topics covered include: - the role of ions and hydration in protein-nucleic acid interactions - transcription factors and combinatorial specificity - indirect readout of DNA sequence - single-stranded nucleic acid binding proteins - nucleic acid junctions and proteins, - RNA protein recognition - recognition of DNA damage. It will be a key reference for both advanced students and established scientists wishing to broaden their horizons.

Book Dissertation Abstracts International

Download or read book Dissertation Abstracts International written by and published by . This book was released on 2008 with total page 994 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Book A Guide to Human Gene Therapy

Download or read book A Guide to Human Gene Therapy written by Roland W. Herzog and published by World Scientific. This book was released on 2010 with total page 415 pages. Available in PDF, EPUB and Kindle. Book excerpt: 1. Non-viral gene therapy / Sean M. Sullivan -- 2. Adenoviral vectors / Stuart A. Nicklin and Andrew H. Baker -- 3. Retroviral vectors and integration analysis / Cynthia C. Bartholomae [und weitere] -- 4. Lentiviral vectors / Janka Matrai, Marinee K.L. Chuah and Thierry VandenDriessche -- 5. Herpes simplex virus vectors / William F. Goins [und weitere] -- 6. Adeno-Associated Viral (AAV) vectors / Nicholas Muzyczka -- 7. Regulatory RNA in gene therapy / Alfred. S. Lewin -- 8. DNA integrating vectors (Transposon, Integrase) / Lauren E. Woodard and Michele P. Calos -- 9. Homologous recombination and targeted gene modification for gene therapy / Matthew Porteus -- 10. Gene switches for pre-clinical studies in gene therapy / Caroline Le Guiner [und weitere] -- 11. Gene therapy for central nervous system disorders / Deborah Young and Patricia A. Lawlor -- 12. Gene therapy of hemoglobinopathies / Angela E. Rivers and Arun Srivastava -- 13. Gene therapy for primary immunodeficiencies / Aisha Sauer, Barbara Cassani and Alessandro Aiuti -- 14. Gene therapy for hemophilia / David Markusic, Babak Moghimi and Roland Herzog -- 15. Gene therapy for obesity and diabetes / Sergei Zolotukhin and Clive H. Wasserfall -- 16. Gene therapy for Duchenne muscular dystrophy / Takashi Okada and Shin'ichi Takeda -- 17. Cancer gene therapy / Kirsten A.K. Weigel-Van Aken -- 18. Gene therapy for autoimmune disorders / Daniel F. Gaddy, Melanie A. Ruffner and Paul D. Robbins -- 19. Gene therapy for inherited metabolic storage diseases / Cathryn Mah -- 20. Retinal diseases / Shannon E. Boye, Sanford L. Boye and William W. Hauswirth -- 21. A brief guide to gene therapy treatments for pulmonary diseases / Ashley T. Martino, Christian Mueller and Terence R. Flotte -- 22. Cardiovascular disease / Darin J. Falk, Cathryn S. Mah and Barry J. Byrne

Book Tumor Suppressor Genes in Human Cancer

Download or read book Tumor Suppressor Genes in Human Cancer written by David E. Fisher and published by Springer Science & Business Media. This book was released on 2000-10-26 with total page 441 pages. Available in PDF, EPUB and Kindle. Book excerpt: David Fisher, MD, PhD, and an authoritative panel of academic, cutting-edge researchers review and summarize the current state of the field. Describing the broad roles of tumor suppressors from a perspective based in molecular biology and genetics, the authors detail the major suppressors and the pathways they regulate, including cell cycle progression, stress responses, apoptosis, and responses to DNA damage. Leading-edge and forward-looking, Tumor Suppressor Genes in Human Cancer illuminates what is currently known of tumor suppressor genes and their regulation, work that is already beginning to revolutionize cancer target elucidation, drug discovery, and treatment design.

Book Principles of Molecular Virology

Download or read book Principles of Molecular Virology written by Alan Cann and published by Elsevier. This book was released on 2005-07-26 with total page 340 pages. Available in PDF, EPUB and Kindle. Book excerpt: "Principles of Molecular Virology, Fourth Edition" provides an essential introduction to modern virology in a clear and concise manner. It is a highly enjoyable and readable text with numerous illustrations that enhance the reader's understanding of important principles. It contains new material on virus structure, virus evolution, zoonoses, bushmeat, SARS and bioterrorism. The standard version includes a CD-ROM with Flash animations, virtual interactive tutorials and experiments, self-assessment questions, useful online resources, along with the glossary, classification of subcellular infectious agents and history of virology.

Book An Introduction to Biotechnology

Download or read book An Introduction to Biotechnology written by W.T. Godbey and published by Elsevier. This book was released on 2014-12-08 with total page 435 pages. Available in PDF, EPUB and Kindle. Book excerpt: An Introduction to Biotechnology is a biotechnology textbook aimed at undergraduates. It covers the basics of cell biology, biochemistry and molecular biology, and introduces laboratory techniques specific to the technologies addressed in the book; it addresses specific biotechnologies at both the theoretical and application levels.Biotechnology is a field that encompasses both basic science and engineering. There are currently few, if any, biotechnology textbooks that adequately address both areas. Engineering books are equation-heavy and are written in a manner that is very difficult for the non-engineer to understand. Numerous other attempts to present biotechnology are written in a flowery manner with little substance. The author holds one of the first PhDs granted in both biosciences and bioengineering. He is more than an author enamoured with the wow-factor associated with biotechnology; he is a practicing researcher in gene therapy, cell/tissue engineering, and other areas and has been involved with emerging technologies for over a decade. Having made the assertion that there is no acceptable text for teaching a course to introduce biotechnology to both scientists and engineers, the author committed himself to resolving the issue by writing his own. - The book is of interest to a wide audience because it includes the necessary background for understanding how a technology works. - Engineering principles are addressed, but in such a way that an instructor can skip the sections without hurting course content - The author has been involved with many biotechnologies through his own direct research experiences. The text is more than a compendium of information - it is an integrated work written by an author who has experienced first-hand the nuances associated with many of the major biotechnologies of general interest today.