Download or read book The Role of the Associated 3 to 5 Exonuclease Activity and Processivity Factor UL42 of Herpes Simplex Virus Type 1 DNA Polymerase on the Fidelity of DNA Replication written by Liping Song and published by . This book was released on 2004 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: Abstract: Herpes simplex virus type 1 (HSV-1) DNA polymerase (pol) has an associated 32 to 52 exonuclease (exo) activity that plays an important role in maintaining the fidelity of DNA replication and viability of the virus. To assess the functional significance of the exo activity, the aspects of fidelity and translesion DNA synthesis affected by HSV-1 pol deficient in this exo activity (D368A) were examined and compared with those of wild-type pol. Because HSV-1 pol forms a stable heterodimer with UL42, a protein that stimulates the polymerizing activity and increases the processivity of pol, the impact of UL42 on fidelity was also evaluated. Pre-steady-state kinetic analysis revealed that the D368A mutation destroyed exo activity without significantly altering the inherent polymerization function. It was demonstrated that both wild-type and mutant pols could selectively incorporate correct vs. incorrect nucleotides, and exo activity enhanced nucleotide selectivity by roughly an order of magnitude under steady-state conditions. However, the primary effect of exo activity on fidelity was manifested during processive DNA synthesis, because it functioned to remove incorporated mismatches, the latter which impeded the extension ability of pol, particularly in the presence of UL42 processivity factor. UL42 did not alter the pre-steady-state rate constants for correct nucleotide incorporation, misincorporation, translocation, or nucleotide excision. However, UL42 decreased dissociation of pol from DNA, which not only made the enzyme more processive but also allowed enough time to excise replication errors. Lesions, such as abasic (AP) sites, also impeded extension beyond the sites, although both HSV-1 wild-type and exo-deficient pols could incorporate dATP opposite the AP site with reduced efficiencies compared to that for normal DNA synthesis. The exo activity facilitated sensing of the lesion through increased excision rate, thereby preventing extension through repeated incorporation and excision events. Taken together, the results of this study suggest that the associated exo activity of HSV-1 pol coordinates with the polymerizing activity by partitioning the primer terminus between the exo and polymerizing sites to proofread errors and prevent translesion synthesis, ultimately increasing the fidelity of HSV-1 DNA synthesis.

Download or read book DNA Replication and Related Cellular Processes written by Jelena Kusic-Tisma and published by BoD – Books on Demand. This book was released on 2011-09-26 with total page 316 pages. Available in PDF, EPUB and Kindle. Book excerpt: Since the discovery of the DNA structure researchers have been highly interested in the molecular basis of genome inheritance. This book covers a wide range of aspects and issues related to the field of DNA replication. The association between genome replication, repair and recombination is also addressed, as well as summaries of recent work of the replication cycles of prokaryotic and eukaryotic viruses. The reader will gain an overview of our current understanding of DNA replication and related cellular processes, and useful resources for further reading.

Download or read book Functional Significance of the Physical Interaction Between the Herpes Simplex Virus Type 1 Origin binding Protein UL9 and the DNA Polymerase Processivity Factor UL42 written by Kelly S. Trego and published by . This book was released on 2003 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: Abstract: The origin (ori)-binding protein of herpes simplex virus type 1 (HSV-1), encoded by the UL9 open-reading frame, has been shown to physically interact with a number of cellular and viral proteins, including three HSV-1 proteins (ICP8, UL42, and UL8) essential for ori-dependent DNA replication. In this report, it is demonstrated for the first time that the DNA polymerase processivity factor, UL42 protein, provides accessory function to the UL9 protein, by enhancing the 3' to 5' helicase activity of UL9 on partially duplex non-specific DNA substrates. UL42 fails to enhance the unwinding activity of a non-cognate helicase, suggesting enhancement of unwinding requires the physical interaction between UL42 and UL9. UL42 increases the steady-state rate for unwinding a 23/38-mer by UL9, but only at limiting UL9 concentrations, consistent with a role in increasing the affinity of UL9 for DNA. Optimum enhancement of unwinding was observed at UL42:UL9 molecular ratios of 4:1, although enhancement was reduced when high ratios of UL42:DNA were present. Under the assay conditions employed, UL42 did not alter the rate of dissociation of UL9 from the DNA substrate. UL42 also did not alter the requirement or time for an assembly/conformational change step, regardless of whether it was added to DNA prior to or at the same time as UL9, or after steady-state unwinding by UL9 alone had been achieved. Thus, the increased affinity of UL9 for DNA most likely is the result of an increase in the association rate constant for binding of UL9 to DNA, and explains why helicase enhancement is observed only at subsaturating concentrations of UL9 with respect to DNA. Consistent with this interpretation are results which demonstrate that UL42 also enhances the ATPase activity of UL9 on single-strand and partially duplex DNA substrates when UL9 is limiting. In contrast, ICP8 enhances unwinding at both saturating and subsaturating UL9 concentrations, and reduces or eliminates the lag period. The different means by which ICP8 and UL42 enhance activities of UL9 suggest that these two members of the presumed functional replisome may act synergistically on UL9 to effect initiation of HSV-1 DNA replication in vivo.

Download or read book The Role of the 3 5 Exonuclease Activity of Herpes Simplex Virus Type 1 in Translesion DNA Synthesis written by Jason Stroud and published by . This book was released on 2005 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: Abstract: Accurate copying of DNA is vital for maintaining genome integrity and organismal viability. The associated 3' to 5' exonuclease (exo) activity of herpes simplex virus (HSV) DNA polymerase (pol) has been shown to play multiple roles in DNA replication error avoidance. The pol-associated exo activity has been shown previously to prevent nascent strand extension in the presence of damaged primer terminus by causing futile cycles of incorporation and excision of nucleotides at the damage site. To further characterize the interaction between the exo and pol domains of the HSV pol catalytic subunit, the ability of exo-deficient (exo- ) and wild-type (wt) pol to extend a DNA primer on a template containing an apyrimidinic (AP) site was assayed. We hypothesized that the communication between the exo and pol domains would allow the enzyme to "look back" to detect an error even after it has replicated through it.

Download or read book Viral Genome Replication written by Craig E. Cameron and published by Springer Science & Business Media. This book was released on 2009-05-28 with total page 636 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book provides the first comprehensive review of viral genome replication strategies, emphasizing not only pathways and regulation but also the structure-function, mechanism, and inhibition of proteins and enzymes required for this process.

Download or read book Cumulated Index Medicus written by and published by . This book was released on 1989 with total page 1506 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Coordination of Th Estrand Displacement Activity of the Herpes Simplex Virus DNA Polymerase written by James Krulisky and published by . This book was released on 2005 with total page 72 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Viral Polymerases written by Satya Prakash Gupta and published by Academic Press. This book was released on 2018-10-29 with total page 498 pages. Available in PDF, EPUB and Kindle. Book excerpt: Viral Polymerases: Structures, Functions and Roles as Antiviral Drug Targets presents in-depth study information on the structure and functions of polymerases and their roles in the lifecycle of viruses, and as drug targets. Viral polymerases constitute a vital component in the lifecycle of many viruses, such as human immunodeficiency virus (HIV), hepatitis viruses, influenza virus, and several others. They are essentially required for the replication of viruses. Thus, the polymerases that can be found in viruses (called viral polymerases) represent favorable targets for the design and development of antiviral drugs. - Provides comprehensive, state-of-the-art coverage on virus infections, the virus lifecycle, and mechanisms of polymerase inhibition - Analyzes the structure-activity relationships of inhibitors of each viral polymerase - Presents a consistent and comprehensive coverage of all aspects of viral polymerases, including structure, function and their role as antiviral drug targets

Download or read book Dissertation Abstracts International written by and published by . This book was released on 2005 with total page 796 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Structure function Analysis of the Herpes Simplex Virus DNA Polymerase Subunit UL42 written by Connie Shui-Yi Chow and published by . This book was released on 1997 with total page 272 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Factors Affecting the Processivity of Herpes Simplex Virus Type 1 DNA Polymerase written by Aaron L. Woofter and published by . This book was released on 1996 with total page 30 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Isolation of Host Proteins Involved in Herpes Simplex Virus Type 1 DNA Synthesis written by Whitney Cogswell and published by . This book was released on 2008 with total page 49 pages. Available in PDF, EPUB and Kindle. Book excerpt: Abstract: Herpes simplex virus type 1 (HSV-1) is the prototypic member of a large family of viruses known as Herpesviridae. Herpesviruses possess a double-stranded DNA genome and infect a broad range of species. In addition to HSV-1, there are seven other herpesviruses that are known to infect humans. Although antiviral treatment is available for HSV infections, there are few or no options for treatment of infections by other herpesviruses. One of the best targets for development of new antivirals is the viral DNA replication apparatus. HSV-1 encodes for seven proteins directly involved in viral DNA replication. However, no HSV-1 origin-dependent DNA replication has been reconstituted in vitro using purified viral proteins. It is hypothesized that proteins (host and/or viral) in addition to the seven known viral DNA replication proteins are involved in viral DNA replication in vivo. Moreover, it is predicted that such proteins would interact with one or more of the viral DNA replication proteins. In an effort to identify interacting host proteins, co-immunoprecipitation analysis was performed using antibodies specific for an essential HSV DNA replication protein, UL42, the polymerase processivity factor. Extracts from infected and mock-infected cells were immunoprecipitated with the UL42 antibody. UL42, and all that is bound to it, bind to the antibody which binds to the Protein G agarose matrix. Those proteins that are specifically pulled down from infected cell extracts, but not from mock-infected extracts, were to be identified by mass-spectrometry. The immunoprecipitates were analyzed following separation on denaturing polyacrylamide gels. Gels were silver-stained or analyzed for the presence of UL42 using a Western blot. Conditions were adjusted to optimize the amount of UL42 immunoprecipitated, but UL42 could not be immunoprecipitated quantitatively. Following immunoprecipitation under optimum conditions, no differences were observed between the proteins pulled-down from mock- or infected-cell extracts. Due to the poor ability of the antibody to pull-down UL42, a second approach was employed. A histidine-tagged version of UL42 was purified using a nickel chelating column and then mixed with infected or mock-infected cell extracts. Those proteins that specifically interact with his-UL42 were expected to bind to a nickel column. However, nonspecific interactions with the matrix were observed and prevented identification of proteins by mass-spectrometry.

Download or read book Jubb Kennedy Palmer s Pathology of Domestic Animals Volume 2 written by Grant Maxie and published by Elsevier Health Sciences. This book was released on 2015-08-14 with total page 1219 pages. Available in PDF, EPUB and Kindle. Book excerpt: With an emphasis on the disease conditions of dogs, cats, horses, swine, cattle and small ruminants, Jubb, Kennedy, and Palmer's Pathology of Domestic Animals, 6th Edition continues its long tradition of being the most comprehensive reference book on common domestic mammal pathology. Using a body systems approach, veterinary pathology experts provide overviews of general system characteristics, reactions to insult, and disease conditions that are broken down by type of infectious or toxic insult affecting the anatomical subdivisions of each body system. The sixth edition now boasts a new full-color design, including more than 2,000 high-resolution images of normal and abnormal organs, tissues, and cells. Updated content also includes evolved coverage of disease agents such as the Schmallenberg virus, porcine epidemic diarrhea virus, and the porcine deltacoronavirus; plus new information on molecular-based testing, including polymerase chain reaction (PCR) and in-situ hybridization, keep you abreast of the latest diagnostic capabilities. - Updated content includes new and evolving pathogens and diagnostic techniques. - Updated bibliographies give readers new entry points into the rapidly expanding literature on each subject. - NEW! High-resolution color images clearly depict the diagnostic features of hundreds of conditions. - NEW! Introduction to the Diagnostic Process chapter illustrates the whole animal perspective and details the approaches to systemic, multi-system, and polymicrobial disease. - NEW! Coverage of camelids is now included in the reference's widened scope of species. - NEW! Team of 30+ expert contributors offers the latest perspective on the continuum of issues in veterinary pathology. - NEW! Expanded resources on the companion website include a variety of helpful tools such as full reference lists with entries linked to abstracts in Pub Med and bonus web-only figures. - NEW! Full-color design improves the accessibility of the text.

Download or read book The Role of the Herpes Simplex Virus Type 1 Alkaline Nuclease in Processing DNA Replication Intermediates written by Joshua Norkin Goldstein and published by . This book was released on 2000 with total page 482 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Essential Human Virology written by Jennifer Louten and published by Academic Press. This book was released on 2022-05-28 with total page 412 pages. Available in PDF, EPUB and Kindle. Book excerpt: Essential Human Virology, Second Edition focuses on the structure and classification of viruses, virus transmission and virus replication strategies based upon type of viral nucleic acid. Several chapters focus on notable and recognizable viruses and the diseases caused by them, including influenza, HIV, hepatitis viruses, poliovirus, herpesviruses and emerging and dangerous viruses. Additionally, how viruses cause disease (pathogenesis) is highlighted, along with discussions on immune response to viruses, vaccines, anti-viral drugs, gene therapy, the beneficial uses of viruses, research laboratory assays and viral diagnosis assays. Fully revised and updated with new chapters on coronaviruses, nonliving infectious agents, and notable non-human viruses, the book provides students with a solid foundation in virology. - Focuses on human diseases and the cellular pathology that viruses cause - Highlights current and cutting-edge technology and associated issues - Presents real case studies and current news highlights in each chapter - Features dynamic illustrations, chapter assessment questions, key terms, and a summary of concepts, as well as an instructor website with lecture slides, a test bank and recommended activities - Updated and revised, with new chapters on coronaviruses, nonliving infectious agents, and notable non-human viruses

Download or read book Nuclear Organization of Herpes Simplex Virus Type 1 Infection written by Jennifer Burkham and published by . This book was released on 2000 with total page 376 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Encyclopedia of Virology written by and published by Academic Press. This book was released on 2021-02-24 with total page 4109 pages. Available in PDF, EPUB and Kindle. Book excerpt: Encyclopedia of Virology, Fourth Edition, Five Volume Set builds on the solid foundation laid by the previous editions, expanding its reach with new and timely topics. In five volumes, the work provides comprehensive coverage of the whole virosphere, making this a unique resource. Content explores viruses present in the environment and the pathogenic viruses of humans, animals, plants and microorganisms. Key areas and concepts concerning virus classification, structure, epidemiology, pathogenesis, diagnosis, treatment and prevention are discussed, guiding the reader through chapters that are presented at an accessible level, and include further readings for those needing more specific information. More than ever now, with the Covid19 pandemic, we are seeing the huge impact viruses have on our life and society. This encyclopedia is a must-have resource for scientists and practitioners, and a great source of information for the wider public. Offers students and researchers a one-stop shop for information on virology not easily available elsewhere Fills a critical gap of information in a field that has seen significant progress in recent years Authored and edited by recognized experts in the field, with a range of different expertise, thus ensuring a high-quality standard