Relevant bibliographies by topics / RNases H

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  1. Journal articles
  2. Dissertations / Theses
  3. Books
  4. Book chapters
  5. Conference papers

Academic literature on the topic 'RNases H'

Author: Grafiati
Published: 4 May 2024

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Journal articles on the topic "RNases H"

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Allen, S. J. W., S. H. Krawczyk, L. R. McGee, N. Bischofberger, A. S. Mulato, and J. M. Cherrington. "Inhibition of HIV-1 RNase H Activity by Nucleotide Dimers and Monomers." Antiviral Chemistry and Chemotherapy 7, no. 1 (February 1996): 37–45. http://dx.doi.org/10.1177/095632029600700107.

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Nucleotide dimers and monomers were shown to inhibit human immunodeficiency virus type 1 (HIV) RNase H activity. Several effective inhibitors were identified and placed into three general groups based on biochemical characterization of their inhibition, The first group (group A) inhibited HIV RNase H and the closely related feline immunodeficiency virus (FIV) RNase H, but did not inhibit less related retroviral or cellular RNases H or HIV reverse transcriptase (RT). The second group (group B) inhibited the RNase H activity of several retroviruses as well as the reverse transcriptase function of HIV RT. The third group (group C) inhibited RNases H from retroviral and cellular sources but did not inhibit HIV RT. Kinetic analyses of HIV RNase H inhibition were conducted and all three types of inhibitors exhibited a competitive mode of inhibition with regard to substrate. The small nucleotides described here represent the most potent (Ki values from 0.57 to 16 μM) and selective inhibitors of HIV RNase H reported to date. Further structure - function analyses of these molecules may lead to the discovery of unique, potent antiretroviral therapeutics.
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Leich, Franziska, Nadine Stöhr, Anne Rietz, Renate Ulbrich-Hofmann, and Ulrich Arnold. "Endocytotic Internalization as a Crucial Factor for the Cytotoxicity of Ribonucleases." Journal of Biological Chemistry 282, no. 38 (July 17, 2007): 27640–46. http://dx.doi.org/10.1074/jbc.m702240200.

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The cytotoxic action of ribonucleases (RNases) requires the interaction of the enzyme with the cellular membrane, its internalization, translocation to the cytosol, and the degradation of ribonucleic acid. The interplay of these processes as well as the role of the thermodynamic and proteolytic stability, the catalytic activity, and the evasion from the intracellular ribonuclease inhibitor (RI) has not yet been fully elucidated. As cytosolic internalization is indispensable for the cytotoxicity of extracellular ribonucleases, we investigated the extent of cytosolic internalization of a cytotoxic, RI-evasive RNase A variant (G88R-RNase A) and of various similarly cytotoxic but RI-sensitive RNase A tandem enzyme variants in comparison to the internalization of the non-cytotoxic and RI-sensitive RNase A. After incubation of K-562 cells with the RNase A variants for 36 h, the internalized amount of RNases was analyzed by rapid cell disruption followed by subcellular fractionation and semiquantitative immunoblotting. The data indicate that an enhanced cellular uptake and an increased entry of the RNases into the cytosol can outweigh the abolishment of catalytic activity by RI. As all RNase A variants proved to be resistant to the proteases present in the different subcellular fractions for more than 100 h, our results suggest that the cytotoxic potency of RNases is determined by an efficient internalization into the cytosol.
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Watkins, Harriet A., and Edward N. Baker. "Structural and Functional Characterization of an RNase HI Domain from the Bifunctional Protein Rv2228c from Mycobacterium tuberculosis." Journal of Bacteriology 192, no. 11 (April 2, 2010): 2878–86. http://dx.doi.org/10.1128/jb.01615-09.

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ABSTRACT The open reading frame Rv2228c from Mycobacterium tuberculosis is predicted to encode a protein composed of two domains, each with individual functions, annotated through sequence similarity searches. The N-terminal domain is homologous with prokaryotic and eukaryotic RNase H domains and the C-terminal domain with α-ribazole phosphatase (CobC). The N-terminal domain of Rv2228c (Rv2228c/N) and the full-length protein were expressed as fusions with maltose binding protein (MBP). Rv2228c/N was shown to have RNase H activity with a hybrid RNA/DNA substrate as well as double-stranded RNase activity. The full-length protein was shown to have additional CobC activity. The crystal structure of the MBP-Rv2228c/N fusion protein was solved by molecular replacement and refined at 2.25-Å resolution (R = 0.182; R free = 0.238). The protein is monomeric in solution but associates in the crystal to form a dimer. The Rv2228c/N domain has the classic RNase H fold and catalytic machinery but lacks several surface features that play important roles in the cleavage of RNA/DNA hybrids by other RNases H. The absence of either the basic protrusion of some RNases H or the hybrid binding domain of others appears to be compensated by the C-terminal CobC domain in full-length Rv2228c. The double-stranded-RNase activity of Rv2228c/N contrasts with classical RNases H and is attributed to the absence in Rv2228c/N of a key phosphate binding pocket.
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Ohtani, Naoto, Mitsuru Haruki, Masaaki Morikawa, and Shigenori Kanaya. "Molecular diversities of RNases H." Journal of Bioscience and Bioengineering 88, no. 1 (January 1999): 12–19. http://dx.doi.org/10.1016/s1389-1723(99)80168-6.

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Hyjek, Malwina, Małgorzata Figiel, and Marcin Nowotny. "RNases H: Structure and mechanism." DNA Repair 84 (December 2019): 102672. http://dx.doi.org/10.1016/j.dnarep.2019.102672.

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Goulian, Mehran, and Cheryl J. Heard. "Discrimination between mammalian RNases H-1 and H-2." Analytical Biochemistry 192, no. 2 (February 1991): 398–402. http://dx.doi.org/10.1016/0003-2697(91)90555-8.

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Lim, Shion A., Kathryn M. Hart, Michael J. Harms, and Susan Marqusee. "Evolutionary trend toward kinetic stability in the folding trajectory of RNases H." Proceedings of the National Academy of Sciences 113, no. 46 (October 31, 2016): 13045–50. http://dx.doi.org/10.1073/pnas.1611781113.

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Proper folding of proteins is critical to producing the biological machinery essential for cellular function. The rates and energetics of a protein’s folding process, which is described by its energy landscape, are encoded in the amino acid sequence. Over the course of evolution, this landscape must be maintained such that the protein folds and remains folded over a biologically relevant time scale. How exactly a protein’s energy landscape is maintained or altered throughout evolution is unclear. To study how a protein’s energy landscape changed over time, we characterized the folding trajectories of ancestral proteins of the ribonuclease H (RNase H) family using ancestral sequence reconstruction to access the evolutionary history between RNases H from mesophilic and thermophilic bacteria. We found that despite large sequence divergence, the overall folding pathway is conserved over billions of years of evolution. There are robust trends in the rates of protein folding and unfolding; both modern RNases H evolved to be more kinetically stable than their most recent common ancestor. Finally, our study demonstrates how a partially folded intermediate provides a readily adaptable folding landscape by allowing the independent tuning of kinetics and thermodynamics.
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Hiller, Bjoern, Martin Achleitner, Silke Glage, Ronald Naumann, Rayk Behrendt, and Axel Roers. "Mammalian RNase H2 removes ribonucleotides from DNA to maintain genome integrity." Journal of Experimental Medicine 209, no. 8 (July 16, 2012): 1419–26. http://dx.doi.org/10.1084/jem.20120876.

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Ribonucleases H (RNases H) are endonucleases which cleave the RNA moiety of RNA/DNA hybrids. Their function in mammalian cells is incompletely understood. RNase H2 mutations cause Aicardi-Goutières syndrome, an inflammatory condition clinically overlapping with lupus erythematosus. We show that RNase H2 is essential in mouse embryonic development. RNase H2–deficient cells proliferated slower than control cells and accumulated in G2/M phase due to chronic activation of a DNA damage response associated with an increased frequency of single-strand breaks, increased histone H2AX phosphorylation, and induction of p53 target genes, most prominently the cyclin-dependent kinase inhibitor 1 encoding cell cycle inhibitor p21. RNase H2–deficient cells featured an increased genomic ribonucleotide load, suggesting that unrepaired ribonucleotides trigger the DNA damage response in these cells. Collectively, we show that RNase H2 is essential to remove ribonucleotides from the mammalian genome to prevent DNA damage.
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Kirby, Karen A., Bruno Marchand, Yee Tsuey Ong, Tanyaradzwa P. Ndongwe, Atsuko Hachiya, Eleftherios Michailidis, Maxwell D. Leslie, et al. "Structural and Inhibition Studies of the RNase H Function of Xenotropic Murine Leukemia Virus-Related Virus Reverse Transcriptase." Antimicrobial Agents and Chemotherapy 56, no. 4 (January 17, 2012): 2048–61. http://dx.doi.org/10.1128/aac.06000-11.

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ABSTRACTRNase H inhibitors (RNHIs) have gained attention as potential HIV-1 therapeutics. Although several RNHIs have been studied in the context of HIV-1 reverse transcriptase (RT) RNase H, there is no information on inhibitors that might affect the RNase H activity of other RTs. We performed biochemical, virological, crystallographic, and molecular modeling studies to compare the RNase H function and inhibition profiles of the gammaretroviral xenotropic murine leukemia virus-related virus (XMRV) and Moloney murine leukemia virus (MoMLV) RTs to those of HIV-1 RT. The RNase H activity of XMRV RT is significantly lower than that of HIV-1 RT and comparable to that of MoMLV RT. XMRV and MoMLV, but not HIV-1 RT, had optimal RNase H activities in the presence of Mn2+and not Mg2+. Using hydroxyl-radical footprinting assays, we demonstrated that the distance between the polymerase and RNase H domains in the MoMLV and XMRV RTs is longer than that in the HIV-1 RT by ∼3.4 Å. We identified one naphthyridinone and one hydroxyisoquinolinedione as potent inhibitors of HIV-1 and XMRV RT RNases H with 50% inhibitory concentrations ranging from ∼0.8 to 0.02 μM. Two acylhydrazones effective against HIV-1 RT RNase H were less potent against the XMRV enzyme. We also solved the crystal structure of an XMRV RNase H fragment at high resolution (1.5 Å) and determined the molecular details of the XMRV RNase H active site, thus providing a framework that would be useful for the design of antivirals that target RNase H.
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Cerritelli, Susana M., and Robert J. Crouch. "RNases H: Multiple roles in maintaining genome integrity." DNA Repair 84 (December 2019): 102742. http://dx.doi.org/10.1016/j.dnarep.2019.102742.

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Dissertations / Theses on the topic "RNases H"

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Pileur, Frédéric. "Les RNases H eucaryotes : étude comparative sur des substrats modèles et obtention d'inhibiteurs aptamétriques sélectifs." Bordeaux 2, 2001. http://www.theses.fr/2001BOR28843.

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Les RNAses H sont des enzymes qui hydrolysent spécifiquement le brin ARN d'un hybride ARN/ADN. Celles-ci sont retrouvées tout au long des règnes animaux et végétaux. Elles participent à l'enlèvement des fragments d'Okazaki lors de la synthèse discontinue de l'ADN. Un rôle dans la transcription est également suspecté. Il existe deux classes de RNases H, la classe I (type 2) et la classe II (type 1), la classification reposant sur des critères biochimiques généraux (sensibilité au NEM, concentration en cations divalents à l'optimum d'activité, poids moléculaire). Tandis que les enzymes de classe I eucaryotes sont localisées dans le noyau, les enzymes de classe II sont retrouvées dans le cytoplasme et la mitochondrie. Les RNases H cellulaires sont aussi connues pour leur action dans les effets d'oligodésoxyribonucléotides antisens. Dans un souci d'optimisation d'oligonucléotides antisens et pour détenir un nouveau critère de classification, nous avons décidé d'étudier le comportement de RNases H eucaryotes de différentes origines sur les hybrides de 20 nucléotides de long. Nous avons analysé les premières coupures de chaque hybride. Il s'est avéré que les RNases HI testées (origine bovine et humaine) préféraient l'extrémité 3' des ARN engagés dans la formation d'hybrides tandis que les RNases HII coupaient à 6 et 8 nucléotides de l'extrémité 5' de ces mêmes ARN. De plus, grâce à ce nouveau critère de nouvelles informations en faveur d'une localisation mitochondriale des RNases HII eucaryotes ont été obtenues. Par la suite nous avons tenté de cloner un gène de RNase HII chez le protozoaire parasite Leishmania mexicana amazonensis. Cette tentative a échoué. Actuellement, très peu d'inhibiteurs de RNases H existent et la stratégie SELEX constitue un bon moyen d'obtenir de tels ligands. Nous avons entrepris une sélection in vitro contre la RNase HII recombinante humaine. A l'issue de la sélection deux aptamères ont retenu notre attention. Le premier, b33, était un bon inhibiteur de la RNase HII avec une IC50 de 120 nM. Cette inhibition était spécifique des RNases HGII eucaryotes. Celui-ci peut se structurer en tige-boucle imparfaite. Le second, b12 n'inhibait que modestement la RNase HII humaine et celui-ci avait la possibilité de former plusieurs structures impliquant des tétrades de G
RNases H are ubiquitous enzymes that hydrolyse the RNA of a DNA/RNA hybrid. They are found in all kingdoms. They participate in the removal of RNA primers of Okazaki fragments. A role in transcription also suspected. RNases H are divided in two classes : class I and class II. RNases HI are nuclear whereasRNases HII are cytoplasmic and mitochondrial. RNases H are also known to be implicated in antisens effects of oligodeoxyribonucleotides. To help in designing new antisens molecules and to possess a new classification criterion, we have analysed the first cuts of these enzymes on various hybrids of 20 nucleotides in length. The tested RNases HI (from bovine and human origin) prefers the 3' end of the RNA engaged in a hybrid whereas RNases HII cut preferentially at 6 and 8 nucleotides from the 5' end of the same RNAs. Moreover informations on mitochondrial localisation of RNases HII has been obtained using this new classification criterion. After this, we have attempted to clone an RNase HII gene from the protozoan Leishmania mexicana amazonensis. This attempt did not succeed. Nowadays, only a few inhibitors of the RNase H activity are known. A good mean to obtain such inhibitors is to use SELEX strategies. We have made an in vitro selection of single stranded DNA aptamers against human recombinant RNase HII. One, b33 inhibited RNaseHII with an IC50 value of 120 nM. This inhibition was specific for eukaryotic RNases HII. B33 could fold into an imperfect stem-loop structure. The second aptamer, b12 poorly inhibited human RNase HII. Moreover several structures could be formed implicating G-quartet formation
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Kemiha, Samira. "Étude du rôle des protéines Ribonucléases H dans la réponse cellulaire au stress réplicatif." Electronic Thesis or Diss., Université de Montpellier (2022-....), 2022. http://www.theses.fr/2022UMONT020.

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Au cours de la phase S, la réplication de l’ADN est initiée au niveau de multiples origines réparties le long du génome. La machinerie de réplication, ou réplisome, peut rencontrer des obstacles ralentissant sa progression, comme des structures secondaires de l’ADN ou des protéines liées à l’ADN telles que les ARN polymérases, générant ainsi ce que l’on appelle un stress réplicatif. Les réplisomes bloqués par un obstacle sont des structures fragiles qui peuvent générer des cassures et conduire à l’instabilité du génome. Lorsque la progression de l’ARN polymérase est ralentie ou arrêtée, le brin d’ARN naissant peut potentiellement s’hybrider avec le brin d’ADN complémentaire en déplaçant le second brin d’ADN, formant ainsi une structure à trois brins appelée R-loop, pouvant entraver la progression du réplisome. La coordination des processus de réplication et de transcription limite les interférences entre la réplication et la transcription. Cependant, cette coordination n’est pas parfaite et même dans des conditions physiologiques, la transcription et l’accumulation de R-loops peuvent conduire à des évènements de recombinaison, notamment au cours de la phase S. Les Ribonucléases H (RNases H) de type 1 et 2 sont des protéines impliquées dans la résolution des R-loops par la dégradation spécifique du brin d’ARN au sein du duplexe ARN:ADN. Les cellules dépourvues de RNases H présentent une accumulation de R-loops et sont extrêmement sensibles à différents agents génotoxiques induisant du stress réplicatif (e.g. MMS : méthanesulfonate de méthyle ou HU : hydroxyurée). Le but de mes travaux de thèse est de déterminer le rôle des RNases H dans la réponse cellulaire au stress réplicatif. Dans deux modèles cellulaires, la levure S. cerevisiae et les cellules humaines, nous avons pu montrer que les cellules déplétées en RNases H présentent des défauts de prise en charge et de redémarrage des fourches de réplication arrêtées en condition de stress réplicatif induit. L'utilisation de mutants de séparation de fonction de RNase H2 suggère que l’élimination défectueuse des hybrides ARN:ADN est responsable de ces défauts. La mesure du taux d’hybrides ARN:ADN au cours du cycle cellulaire montre qu’il augmente en phase S en présence de stress réplicatif exogène dans des cellules sauvages et mutantes pour RNases H. De plus, nos résultats indiquent que l’inhibition de la transcription ou la surexpression de l’hélicase ARN:ADN Sénataxine restaure la prise en charge et le redémarrage des fourches de réplication arrêtées lors d’un stress induit par le MMS et en absence des RNases H. Ainsi, l’ensemble de nos résultats suggère une étroite coopération entre les Ribonucléases H et l’hélicase Sénataxine pour résoudre les interférences entre les ARN polymérases et/ou les hybrides ARN:ADN avec les machineries de réplication
During S phase, DNA replication starts at multiple origins distributed throughout the genome. As the replication machinery (or replisome) progresses throughout the DNA, it often encounters obstacles such as DNA secondary structures or transcription complexes, thereby generating what is called replication stress. Stalled replisomes are fragile structures that can give rise to chromosome breaks and trigger genome instability. When RNA polymerases stall, the nascent RNA can potentially anneal with the template DNA strand, creating a three-strand structure called R-loop. Coordination between replication and transcription in S phase limits the risks of collisions between the replisome and RNA polymerases. Even though, physiological transcription level and R-loops accumulation lead to recombination events in S phase. Type 1 and 2 ribonucleases H (RNase H) are specific proteins involved R-loops’ resolution through the degradation of the RNA strand within the RNA:DNA duplex. In the absence of RNases H, cells accumulate R-loops and are extremely sensitive to different replication stress-inducing genotoxic agents (e.g. MMS: methyl methanesulfonate or HU: hydroxyurea).The goal of my PhD project was to assess the roles of RNases H in the cellular response to replication stress. Using two cellular models, the budding yeast S. cerevisiae and mammalian cells, we demonstrated that RNases H mutations induce HU- and MMS-stalled replication forks processing and restart defects. Analysis of separation-of-function RNase H2 mutants suggests that it is the RNA:DNA hybrids removal activity of RNase H2 that is important for the correct processing of stalled forks experiencing replication stress. Indeed, quantification of RNA:DNA hybrids during the cell cycle reveals a higher level of hybrids in S phase in the presence of exogenous replication stress in both wild-type and RNases H-depleted cells. Moreover, our results demonstrate that the inhibition of transcrip tion or the overexpression of the RNA:DNA helicase Senataxin restore stalled replication fork processing and restart upon MMS treatment when cells lack RNase H2 activities. Altogether, our data indicate that Ribonucleases H1 and 2 and Senataxin helicase cooperate to resolve RNA polymerases and/or RNA:DNA hybrids interferences with replication
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Pâtureau, Bénédicte Marie. "Induction of rnase H activity by arabinose-peptide nucleic acids." Thesis, McGill University, 2005. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=98763.

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Antisense oligonucleotides (AON) offer a rational approach for drug design. The specificity of AONs towards a complementary messenger RNA (mRNA) target via Watson and Crick base pairing as well as their ease of synthesis render this technology very attractive. RNase H-degradation of mRNA via formation of a AON/mRNA hybrid is crucial to mainstream antisense technologies. Numerous studies have demonstrated the importance of the AON's structure and conformational flexibility for efficient induction of RNase H activity. However the precise mode of action and substrate specificity of the RNase H are not fully understood at present. Our Laboratory recently discovered that incorporation of flexible acyclic linkers (e.g. butanediol, 2'-seco-RNA) significantly amplifies enzyme activity. Unfortunatly incorporation of such linkers was accompanied by a drop in the thermal stability of the AON/RNA hybrids. This prompted us to incorporate a less flexible linker such as a peptide nucleic acid, with the hope to maintain similar enzymatic activity while increasing the duplex thermal stability.
This thesis highlights the synthesis of the 5'-amino nucleoside analogue required for the incorporation of the peptide nucleic acid in both 2'-fluoroarabinonucleic acid (2'F-ANA) and DNA. Circular dichroism experiments afforded information on the hybrid conformation in solution, whereas UV thermal melting studies provided a measure of the thermal stability of such hybrid duplexes. Finally, ability of various linker modified AON/RNA hybrids to activate the RNase H enzyme was evaluated in parallel with the corresponding native unmodified DNA/RNA hybrids.
Incorporation of a PNA residue within DNA or 2'-FANA did not afford improvement in neither thermal stability nor enzymatic cleavage (except for homopolymeric sequences vs DNA) as compared to control or butyl-sequences.
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Yang, Taehwan. "Understanding the relation between RNase H and retrotransposition activity in the context of the Aicardi-Goutieres syndrome." Thesis, Georgia Institute of Technology, 2014. http://hdl.handle.net/1853/53997.

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Ribonucleases (RNases) H1 and H2 are endonucleases that hydrolyze the RNA strand of RNA-DNA hybrids forming at the chromosomal level as well as extra-chromosomal hybrids. Extra-chromosomal RNA-DNA hybrids can frequently occur in cells as intermediate structures in the process of reverse transcription and generation of cDNA by retrotransposition. It is known that mutations in RNase H2 are found in Aicardi-Goutières syndrome (AGS) patients. AGS is a rare but severe immune-mediated neurodevelopmental disorder. Currently, the mechanism by which defects in RNase H2 cause AGS is still unclear. We hypothesized that defects in RNases H, including those associated with AGS can trigger the accumulation of extra-chromosomal RNA-DNA hybrids. Thus, we speculate that increased stability of such free RNA-DNA hybrid structures could be a likely trigger for stimulating the autoimmune system, mimicking a viral infection in AGS patients. RNase H2 protein subunits of human and yeast Saccharomyces cerevisiae RNase H2 proteins have conserved amino acid sequences. Based on the similarity between human and yeast RNase H2, we thought to utilize S. cerevisiae as a research model to generate and study several AGS-related mutants. Initially, we set up an assay to detect retrotransposition activity in the budding yeast by introducing a recombinant DNA which includes a Ty1 retrotransposable element fused to an inactive his3 marker gene. To test whether the retrotransposition assay works in our yeast strains, we treated yeast cells with phosphonoformic acid (PFA) or knocked out DBR1 gene coding for the RNA lariat debranching enzyme. Both approaches strongly reduced the frequency of retrotransposition in our strains, demonstrating that the system was working as expected. Next, we examined whether yeast cells with defective forms of RNases H or AGS-orthologous mutants of RNase H2 had altered retrotransposition activity compared with cells with wild-type RNases H. Results showed that the retrotransposition activity was repressed in the absence of both types of RNase H. In addition, AGS-related mutants showed decreased retrotransposition frequencies when RNase H1 was also knocked-out. These findings are relevant to uncover the mechanism of the AGS.
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CORONA, ANGELA. "Characterization of the mechanism of action of new HIV-1 reverse transcriptase-associated ribonuclease H inhibitors." Doctoral thesis, Università degli Studi di Cagliari, 2014. http://hdl.handle.net/11584/266462.

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HIV-1 the Reverse Transcriptase (RT), the most renowned retroviral specific enzyme, was the first anti-HIV target to be exploited, as. HIV-1 RT combines two functions essential for viral replication: DNA polymerase, synthesis DNA either in a RNA dependent (RDDP) or DNA dependent (DDDP) manner, and Ribonuclease H (RNase H) . The RNase H activity catalyzes highly specific hydrolytic events on the RNA strand of the RNA/DNA replication intermediate, critical to the synthesis of integration-competent double-stranded proviral DNA. Because of its essential role, RNase H is a promising target for drug development. However, despite years of efforts, no RNase H inhibitor (RHI) has yet reached clinical approval. In this work we pursued the identification and characterization of new promising RHIs targeting either the RNase H active site itself (RNase H active site chelating agents) or both RNase H and RDDP activities (allosteric dual inhibitors). The first approach faced the challenging nature of the RNase H active site region, the morphology of wich is, more open than that of the relatively similar,HIV-1 integrase (IN). This hampers the identification of a druggable pocket. We initially used Foamy Virus RT as a tool, to perform NMR and docking analyses on the interaction between FV RT RNase H domain and a previously identified diketo acid (DKA) derivative, inhibitor RDS1643. The amino acid residues of the FV RNase H active site region (T641, I647, Y672 and W703) were established to be important for the interaction with the inhibitor and analogous residues were successfully identified in the HIV-1 RNase H domain using structural overlays. Further docking and site directed mutagenesis studies were performed using six couples of ester/acid DKA, derived from RDS1643, showing for the first time, a broad interaction between RHIs and conserved residues in the HIV-1 RNase H active site region (R448, N474, Q475, Y501 and R557). Moreover, ester and acid derivatives exhibited a different binding orientation, that reflected a different specificity for RNase H versus IN. Among the synthesised derivatives one, RDS1759, showed to be an RNase H selective active site inhibitor characterized also, for the first time,in cell-based assays. The second approach focused on the determination of the mechanism of action of a new isatine-derived RNase H/RDDP dual inhibitor, RMNC6. Docking analysis and site directed mutagenesis results suported the hypothesis of a two-sites mode of action, with an independent role for two pockets,to be further characterized for a rational optimization of the scaffold.
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Acosta-Hoyos, Antonio J. "Relationship Between RNase H and Excision Activities of HIV-1 Reverse Transcriptase (RT)." Scholarly Repository, 2010. http://scholarlyrepository.miami.edu/oa_dissertations/458.

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Replication of HIV-1 is inhibited by azidothymidine (AZT), which leads to chain termination and inhibition of DNA synthesis. Resistance to AZT is frequently the result of mutations that increase the ability of RT to remove the chain-terminating nucleotides after they have been incorporated. It has been proposed that RNase H cleavage of the RNA template can occur when RT is stalled near the site of chain termination and contributes to the inhibition by causing the dissociation of the primer-template before the chain terminator can be excised. Mutations in the connection and RNase H domains of RT have been shown to increase excision. It has long been known that resistance to thymidine analogs is conferred by the mutations M41L, D67N, K70R, L210W, T215F/Y and T219Q/E in RT and that this resistance is suppressed by the additional presence of the M184V mutation. Changes in excision activity on DNA templates have been observed with these mutant RTs, but effects on RNase H cleavage resulting in indirect effects on excision activity is also possible with RNA templates. We used a 5'-labeled -3'-chain-terminated DNA primer annealed to either a DNA or RNA template to evaluate primer rescue activities, a 5'-labeled RNA template to evaluate RNA cleavage activity and a biotin-tagged chain-terminated oligodeoxynucleotide to monitor primer-template dissociation. We first investigated differences between RNA and DNA templates when the primers were chain terminated and observed a correlation between RNase H activities and template/primer (T/P) dissociation. An inverse correlation was observed between excision rescue rates and RNase H cleavages leading to T/P dissociation. We observed that the chain terminator (i.e. AZTMP or ddAMP) affected RNase H cleavages and excision rates with RNA template and dNTPs. When we investigated mutations in the N-terminal domain of RT associated with nucleoside reverse transcriptase inhibitor (NRTI) resistance we found that primer rescue was decreased when M184V was present in combination with thymidine analog mutations (TAMs) and the template was RNA with either ATP or PPi as excision substrate. RNase H cleavage at secondary cleavage sites (-7, -8) was substantially reduced with M41L/T215Y RT in comparison with wild type RT, and primer-template dissociation was decreased. In contrast, when M184V was present, RNase H cleavage at the secondary cleavage sites and dissociation of the primer-template occurred at higher levels and excision rescue was decreased. The ability of RT to rescue an AZT terminated primer in the presence of the 184V mutation was restored when the RNase H activity was inactivated by the RNase H negative mutation E478Q. Electromobility shift assay (EMSA) analysis of AZT-resistant mutant RT with M184V showed an increased Kd for formation of the ternary complex. These results suggest that RNase H-mediated RNA-DNA template-primer dissociation is influenced by mutations associated with thymidine analog resistance, and that suppression of resistance to nucleoside RT inhibitors by M184V may be partly explained by effects on RNase H cleavage that decrease the time available for excision to occur. This is the first time that mutations in the polymerase domain are shown to affect excision rescue through an RNase H-dependent mechanism.
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Leo, Berit [Verfasser], and Birgitta [Akademischer Betreuer] Wöhrl. "Foamy Virus RNase H - Aktivität, Struktur und Funktion / Berit Leo. Betreuer: Birgitta Wöhrl." Bayreuth : Universität Bayreuth, 2013. http://d-nb.info/1059352982/34.

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Becaud, Jessica. "Towards RNase H mimics : artificial catalysts for the site specific cleavage of RNA /." [S.l.] : [s.n.], 2005. http://www.zb.unibe.ch/download/eldiss/05becaud_j.pdf.

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Schönewolf, Nicola. "Mutationen in der Connection und RNAse H-Domain der Reversen Transkriptase von HIV-1." Diss., lmu, 2010. http://nbn-resolving.de/urn:nbn:de:bvb:19-121176.

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Larrouy, Béatrice. "Effets sur la traduction d'oligonucléotides chimiquement modifiés : contribution de la RNase H, modulation post-transcriptionnelle." Bordeaux 2, 1996. http://www.theses.fr/1996BOR28413.

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Books on the topic "RNases H"

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Blain, Stacy Wister. Structure-function studies of Moloney murine leukemia virus RNase H. 1995.

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Book chapters on the topic "RNases H"

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Ponchon, Luc, Geneviève Beauvais, Sylvie Nonin-Lecomte, and Frédéric Dardel. "Selective RNase H Cleavage of Target RNAs from a tRNA Scaffold." In Recombinant and In Vitro RNA Synthesis, 9–18. Totowa, NJ: Humana Press, 2012. http://dx.doi.org/10.1007/978-1-62703-113-4_2.

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Hollis, Thomas, and Nadine M. Shaban. "Structure and Function of RNase H Enzymes." In Nucleic Acids and Molecular Biology, 299–317. Berlin, Heidelberg: Springer Berlin Heidelberg, 2011. http://dx.doi.org/10.1007/978-3-642-21078-5_12.

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Nowotny, Marcin, and Małgorzata Figiel. "The RNase H Domain: Structure, Function and Mechanism." In Human Immunodeficiency Virus Reverse Transcriptase, 53–75. New York, NY: Springer New York, 2013. http://dx.doi.org/10.1007/978-1-4614-7291-9_3.

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Moelling, Karin, Felix Broecker, and John E. Kerrigan. "RNase H: Specificity, Mechanisms of Action, and Antiviral Target." In Methods in Molecular Biology, 71–84. Totowa, NJ: Humana Press, 2014. http://dx.doi.org/10.1007/978-1-62703-670-2_7.

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Tachedjian, Gilda, and Nicolas Sluis-Cremer. "Role of RNase H Activity in NRTI/NNRTI Drug Resistance." In Human Immunodeficiency Virus Reverse Transcriptase, 281–303. New York, NY: Springer New York, 2013. http://dx.doi.org/10.1007/978-1-4614-7291-9_13.

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Arvola, René M., and Aaron C. Goldstrohm. "Measuring Poly-Adenosine Tail Length of RNAs by High-Resolution Northern Blotting Coupled with RNase H Cleavage." In Methods in Molecular Biology, 93–111. New York, NY: Springer US, 2023. http://dx.doi.org/10.1007/978-1-0716-3481-3_6.

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Seth, Punit P., and Eric E. Swayze. "CHAPTER 3. The Medicinal Chemistry of RNase H-activating Antisense Oligonucleotides." In Drug Discovery, 32–61. Cambridge: Royal Society of Chemistry, 2019. http://dx.doi.org/10.1039/9781788015714-00032.

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Wei, Fenju, Edeildo Ferreira da Silva-Júnior, Xinyong Liu, and Peng Zhan. "HIV-1 and HBV RNase H as Metal-Chelating Inhibitors: Discovery and Medicinal Chemistry Strategies." In Human Viruses: Diseases, Treatments and Vaccines, 585–602. Cham: Springer International Publishing, 2021. http://dx.doi.org/10.1007/978-3-030-71165-8_28.

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Moelling, K., M. Nawrath, T. Schulze, L. Pavlitzkova, M. Soucek, K. H. Budt, L. H. Pearl, M. T. Knoop, J. Kay, and V. Kruft. "Cleavage of RT/RNase H by HIV-1 Protease and Analysis of Substrate Cleavage Sites in vitro." In Retroviral Proteases, 19–29. London: Macmillan Education UK, 1990. http://dx.doi.org/10.1007/978-1-349-11907-3_4.

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Matthews, David A., Jay F. Davies, Zuzana Hostomska, Zdenek Hostomsky, and Steven R. Jordan. "Three-dimensional structure of the RNase H domain of HIV-1 reverse transcriptase at 2. 4 Å resolution." In Peptides, 682–84. Dordrecht: Springer Netherlands, 1992. http://dx.doi.org/10.1007/978-94-011-2264-1_272.

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Conference papers on the topic "RNases H"

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Sun, Yewei. "The role of eukaryotic RNase H in R-loop resolution." In Third International Conference on Biological Engineering and Medical Science (ICBioMed2023), edited by Alan Wang. SPIE, 2024. http://dx.doi.org/10.1117/12.3012930.

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