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| calf thymus ribonuclease hSummarySummary: A ribonuclease that specifically cleaves the RNA moiety of RNA:DNA hybrids. It has been isolated from a wide variety of prokaryotic and eukaryotic organisms (particularly calf thymus) as well as retroviruses. EC 3.1.26.4. Top Publications
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Publications
The involvement of human ribonucleases H1 and H2 in the variation of response of cells to antisense phosphorothioate oligonucleotidesAnneloor L M A ten Asbroek
Neurozintuigen Laboratory, Academic Medical Center, Amsterdam, The Netherlands
Eur J Biochem 269:583-92. 2002..RNase H2 is involved in the activity assayed in vitro. The presence of cell-type specific factors affecting the activity and localization of RNase H2 is strongly suggested...
Mutations in yeast replication proteins that increase CAG/CTG expansions also increase repeat fragilityJulie L Callahan
Department of Biology, Program in Genetics, Tufts University, Medford, Massachusetts 02155, USA
Mol Cell Biol 23:7849-60. 2003..These results suggest that processes that generate strand breaks, such as faulty Okazaki fragment processing or DNA repair, are an important source of TNR expansions...
Selective inhibitory DNA aptamers of the human RNase H1Frédéric Pileur
INSERM U386, IFR Pathologies Infectieuses, Universite Victor Segalen Bordeaux 2, 146, rue Leo Saignat, 33076 Bordeaux Cedex, France
Nucleic Acids Res 31:5776-88. 2003..Finally, the inhibitory aptamers were capable of completely abolishing the action of an antisense oligonucleotide in a rabbit reticulocyte lysate supplemented with human RNase H1, with IC50 ranging from 50 to 100 nM...
Nonpolar thymine isosteres in the Ty3 polypurine tract DNA template modulate processing and provide a model for its recognition by Ty3 reverse transcriptaseDaniela Lener
Resistance Mechanisms Laboratory, HIV Drug Resistance Program, NCI-Frederick, National Institutes of Health, Frederick, Maryland 21702-1201, USA
J Biol Chem 278:26526-32. 2003....
Specific cleavages by RNase H facilitate initiation of plus-strand RNA synthesis by Moloney murine leukemia virusSharon J Schultz
Department of Microbiology, School of Medicine, University of Washington, Seattle 98195-7242, USA
J Virol 77:5275-85. 2003..These data suggest a model in which efficient initiation of plus-strand synthesis requires the generation of a gap immediately following the plus-strand primer 3' terminus...
Failure to produce mitochondrial DNA results in embryonic lethality in Rnaseh1 null miceSusana M Cerritelli
Laboratory of Molecular Genetics, National Institutes of Health, Bethesda, MD 20892, USA
Mol Cell 11:807-15. 2003..These findings also have important implications for therapy of mitochondrial dysfunctions and drug development for the structurally related RNase H of HIV...
Dissecting the effects of DNA polymerase and ribonuclease H inhibitor combinations on HIV-1 reverse-transcriptase activitiesCathryn A Shaw-Reid
Department of Antiviral Research, Merck Research Laboratories, West Point, Pennsylvania 19486-0004, USA
Biochemistry 44:1595-606. 2005....
Mechanism for nucleoside analog-mediated abrogation of HIV-1 replication: balance between RNase H activity and nucleotide excisionGalina N Nikolenko
Viral Mutation Section, HIV Drug Resistance Program, National Cancer Institute, Frederick, MD 21702, USA
Proc Natl Acad Sci U S A 102:2093-8. 2005....
Using pyrrolo-deoxycytosine to probe RNA/DNA hybrids containing the human immunodeficiency virus type-1 3' polypurine tractChandravanu Dash
Resistance Mechanisms Laboratory, HIV Drug Resistance Program, National Cancer Institute-Frederick, Frederick, MD 21702, USA
Nucleic Acids Res 32:1539-47. 2004..pdC substitution within the template strand of a DNA duplex does not appear to significantly affect RT-catalyzed DNA synthesis. Implications of these findings on the use of pdC to examine nucleic acid structure are discussed...
Uncovering the complexities of retroviral ribonuclease H reveals its potential as a therapeutic targetGeorge J Klarmann
Reverse Transcriptase Biochemistry Section, HIV Drug Resistance Program, National Cancer Institute, Frederick, P.O. Box B Frederick, MD 21702, USA
AIDS Rev 4:183-94. 2002..Our current understanding of retroviral RNase H function and the status of small molecule inhibitors are the focus of this review...
Crystal structures of RNase H bound to an RNA/DNA hybrid: substrate specificity and metal-dependent catalysisMarcin Nowotny
Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA
Cell 121:1005-16. 2005..In transposases, they are symmetrically coordinated and exchange roles to alternately activate a water and a 3'-OH for successive strand cleavage and transfer by a ping-pong mechanism...
Synthesis and properties of oligonucleotide chimeras containing 5'-amino-2'-deoxy-2'-fluoroarabinonucleosidesEkaterina Viazovkina
Department of Chemistry, McGill University, Montreal, Quebec, Canada
Nucleosides Nucleotides Nucleic Acids 22:1335-8. 2003..The corresponding relative rates observed with the human enzyme were: gap DNA > 2'F-ANA(5'N) > 2'F-ANA > DNA(5'N)...
Efficient reduction of target RNAs by small interfering RNA and RNase H-dependent antisense agents. A comparative analysisTimothy A Vickers
GeneTrove Division and Antisense Core Research Department, Isis Pharmaceuticals, Inc, Carlsbad, California 92008, USA
J Biol Chem 278:7108-18. 2003..These results demonstrate that siRNA oligonucleotide- and RNase H-dependent antisense strategies are both valid strategies for evaluating function of genes in cell-based assays...
Inhibition of HIV-1 ribonuclease H by a novel diketo acid, 4-[5-(benzoylamino)thien-2-yl]-2,4-dioxobutanoic acidCathryn A Shaw-Reid
Department of Biological Chemistry, Merck Research Laboratories, West Point, Pennsylvania 19486 0004, USA
J Biol Chem 278:2777-80. 2003....
Effects of mutations in the G tract of the human immunodeficiency virus type 1 polypurine tract on virus replication and RNase H cleavageJohn G Julias
HIV Drug Resistance Program, NCI-Frederick, P.O. Box B, Building 539, Room 130A, Frederick, MD 21702-1201, USA
J Virol 78:13315-24. 2004..This result is consistent with the idea that the 3' end-processing reactions of retroviral integrases may help to generate defined ends from a heterogenous population of linear viral DNAs...
Crystal structure of Argonaute and its implications for RISC slicer activityJi Joon Song
Watson School of Biological Sciences, 1 Bungtown Road, Cold Spring Harbor, NY 11724, USA
Science 305:1434-7. 2004..quot; The architecture of the molecule and the placement of the PAZ and PIWI domains define a groove for substrate binding and suggest a mechanism for siRNA-guided mRNA cleavage...
Determination of the role of the human RNase H1 in the pharmacology of DNA-like antisense drugsHongjiang Wu
Department of Core Technology, Isis Pharmaceuticals, Inc, Carlsbad, California 92008, USA
J Biol Chem 279:17181-9. 2004..Further, we show that there are several additional previously undescribed RNases H in human cells that may participate in the effects of DNA-like antisense oligonucleotides...
A fluorescence-based high-throughput screening assay for inhibitors of human immunodeficiency virus-1 reverse transcriptase-associated ribonuclease H activityMichael A Parniak
Department of Medicine, University of Pittsburgh, Pittsburgh, PA 15261, USA
Anal Biochem 322:33-9. 2003..Several chemical libraries totaling more than 106,000 compounds were screened with this assay in approximately 1 month...
An unusual sugar conformation in the structure of an RNA/DNA decamer of the polypurine tract may affect recognition by RNase HMary L Kopka
Molecular Biology Institute, University of California, Los Angeles, CA 90095 1570, USA
J Mol Biol 334:653-65. 2003..Disruption could cause the enzyme to pause at the 5'-end of the PPT, leaving it intact. Pyrimidine-purine (YR) steps are most deformable and the T-A step especially can undergo A-to-B transitions readily...
Two-metal ion mechanism of RNA cleavage by HIV RNase H and mechanism-based design of selective HIV RNase H inhibitorsKlaus Klumpp
Roche Discovery Welwyn, Welwyn Garden City, UK
Nucleic Acids Res 31:6852-9. 2003..Based on this difference in active site structure, a series of small molecule N-hydroxyimides was identified with significant enzyme inhibitory potency and selectivity for HIV RNase H...
'Binding, bending and bonding': polypurine tract-primed initiation of plus-strand DNA synthesis in human immunodeficiency virusJason W Rausch
Reverse Transcriptase Biochemistry Section, HIV Drug Resistance Program, National Cancer Institute at Frederick, Building 535, Room 325, Frederick, MD 21702, USA
Int J Biochem Cell Biol 36:1752-66. 2004..In this review, plus-strand primer processing in HIV-1 is discussed from biochemical, structural, and historical perspectives. A comparative analysis of PPT-processing in different LTR-containing retroelements is also presented...
Cotranscriptionally formed DNA:RNA hybrids mediate transcription elongation impairment and transcription-associated recombinationPablo Huertas
Departamento de Genetica, Facultad de Biologia, Universidad de Sevilla, Avenida Reina, Mercedes 6, 41012 Seville, Spain
Mol Cell 12:711-21. 2003..These data support a model to explain the connection between recombination, transcription, and mRNA metabolism and provide a new perspective to understanding transcription-associated recombination...
Mutations in the 5' end of the human immunodeficiency virus type 1 polypurine tract affect RNase H cleavage specificity and virus titerMary Jane McWilliams
HIV-Drug Resistance Program, Frederick Cancer Research and Development Center, National Cancer Institute, Frederick, Maryland 21702-1201, USA
J Virol 77:11150-7. 2003..The mutants tested preferentially retained specific segments of the PPT, suggesting an effect on cleavage specificity. These results suggest that structural features of the PPT are important for its recognition and cleavage in vivo...
Structural requirements at the catalytic site of the heteroduplex substrate for human RNase H1 catalysisWalt F Lima
Department of Molecular and Structural Biology, Isis Pharmaceuticals, 2292 Faraday Avenue, Carlsbad, CA 92008, USA
J Biol Chem 279:36317-26. 2004....
Two modes of HIV-1 polypurine tract cleavage are affected by introducing locked nucleic acid analogs into the (-) DNA templateChandravanu Dash
Resistance Mechanisms Laboratory, HIV Drug Resistance Program, NCI-Frederick, National Institutes of Health, Frederick, MD 21702, USA
J Biol Chem 279:37095-102. 2004....
A capillary electrophoretic assay for ribonuclease H activityKing C Chan
Laboratory of Proteomics and Analytical Technologies, SAIC-Frederick, Inc, Center for Cancer Research, NCI at Frederick, Frederick, MD 21702, USA
Anal Biochem 331:296-302. 2004..The assay was broadly applicable to other RNases H, specifically those from human, Escherichia coli, and HIV-2, although product profiles varied for each enzyme...
Sequence, distance, and accessibility are determinants of 5'-end-directed cleavages by retroviral RNases HSharon J Schultz
Department of Microbiology, School of Medicine, University of Washington, Seattle, WA 98195, USA
J Biol Chem 281:1943-55. 2006..Together these finding demonstrate that the selection of 5'-end-directed cleavage sites by retroviral RNases H results from a combination of nucleotide sequence, permissible distance, and accessibility to the RNA 5'-end...
Examining Ty3 polypurine tract structure and function by nucleoside analog interferenceChandravanu Dash
Resistance Mechanisms Laboratory, HIV Drug Resistance Program, NCI-Frederick, National Institutes of Health, Frederick, Maryland 21702, USA
J Biol Chem 281:2773-83. 2006....
Fabricating RNA microarrays with RNA-DNA surface ligation chemistryHye Jin Lee
Department of Chemistry, University of California-Irvine, 92697, USA
Anal Chem 77:7832-7. 2005..These RNA microarrays can be used in the study of RNA-protein/RNA/aptamer bioaffinity interactions and for the enzymatically amplified SPRI detection of DNA in the presence of RNase H...
Stepwise analyses of metal ions in RNase H catalysis from substrate destabilization to product releaseMarcin Nowotny
Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA
EMBO J 25:1924-33. 2006..Lastly, product release probably requires dissociation of metal ion A, which is inhibited by either high concentrations of divalent cations or mutation of an assisting protein residue...
Mutations of the RNase H C helix of the Moloney murine leukemia virus reverse transcriptase reveal defects in polypurine tract recognitionDavid Lim
Integrated Program in Cellular, Molecular and Biophysical Studies, Howard Hughes Medical Institute, College of Physicians and Surgeons, Columbia University, New York, New York 10032, USA
J Virol 76:8360-73. 2002..The data also suggest that the C helix may play an important role in polypurine tract recognition and proper formation of the plus-strand DNA's 5' end...
Altering the RNase H primer grip of human immunodeficiency virus reverse transcriptase modifies cleavage specificityJason W Rausch
HIV Drug Resistance Program, National Cancer Institute-Frederick, Frederick, Maryland 21702, USA
Biochemistry 41:4856-65. 2002..Reduced polymerization-independent RNase H activity also significantly influenced the rate of DNA strand transfer, suggesting the donor template must be reduced in size below 13 nt before this event proceeds...
Potent gene-specific inhibitory properties of mixed-backbone antisense oligonucleotides comprised of 2'-deoxy-2'-fluoro-D-arabinose and 2'-deoxyribose nucleotidesChun-Nam Lok
Lady Davis Institute for Medical Research, Department of Medicine, McGill University, Montreal, Quebec PQ, Canada H3A 2K6
Biochemistry 41:3457-67. 2002....
Mutations in the ribonuclease H active site of HIV-RT reveal a role for this site in stabilizing enzyme-primer-template bindingJason V Cristofaro
Department of Cell Biology and Molecular Genetics, University of Maryland College Park, Building 231, College Park, Maryland 20742, USA
Biochemistry 41:10968-75. 2002..In this regard RT is similar to other nucleic acid cleaving enzymes that show enhanced binding upon mutation of active site residues...
Oligonucleotides comprised of alternating 2'-deoxy-2'-fluoro-beta-D-arabinonucleosides and D-2'-deoxyribonucleosides (2'F-ANA/DNA 'altimers') induce efficient RNA cleavage mediated by RNase HKyung-Lyum Min
Department of Chemistry, McGill University, 801 Sherbrooke Street West, H3A 2K6, Montreal, QC, Canada
Bioorg Med Chem Lett 12:2651-4. 2002....
Efficient RNase H-directed cleavage of RNA promoted by antisense DNA or 2'F-ANA constructs containing acyclic nucleotide insertsMaria M Mangos
Contribution from McGill University, Department of Chemistry, Montreal, QC, Canada
J Am Chem Soc 125:654-61. 2003....
Chimeric RNA-DNA molecular beacon assay for ribonuclease H activityJ Rizzo
Department of Chemistry, School of Arts and Sciences, University of Pennsylvania, Philadelphia, PA, 19104, USA
Mol Cell Probes 16:277-83. 2002..This method permits real-time detection of RNase H activity and a convenient approach to RNase H kinetic and mechanistic study...
Pre-existing distortions in nucleic acid structure aid polypurine tract selection by HIV-1 reverse transcriptaseMamuka Kvaratskhelia
Reverse Transcriptase Biochemistry Section, Resistance Mechanisms Laboratory, HIV Drug Resistance Program, NCI-Frederick, National Institutes of Health, Frederick, Maryland 21702, USA
J Biol Chem 277:16689-96. 2002..Our data collectively suggest that the entire PPT sequence contributes to the structural distortion at the PPT/U3 junction, potentially providing a mechanism for its selective processing...
Human RNase H1 uses one tryptophan and two lysines to position the enzyme at the 3'-DNA/5'-RNA terminus of the heteroduplex substrateWalt F Lima
Department of Molecular and Structural Biology, Isis Pharmaceuticals, Carlsbad, California 92008, USA
J Biol Chem 278:49860-7. 2003..These results offer further insights into the interaction between human RNase H1 and the heteroduplex substrate as well as approaches to enhance the design of effective antisense oligonucleotides...
Mutating conserved residues in the ribonuclease H domain of Ty3 reverse transcriptase affects specialized cleavage eventsDaniela Lener
Reverse Transcriptase Biochemistry Section, Resistance Mechanisms Laboratory, HIV Drug Resistance Program, NCI-Frederick, National Institutes of Health, Frederick, Maryland 21702, USA
J Biol Chem 277:26486-95. 2002..DNA hybrid failed to support DNA strand transfer and release of the (+) strand polypurine tract primer from (+) RNA, suggesting that interrupting one or both of these events might account for the transposition defect...
Expression of the C-terminus of HIV-1 reverse transcriptase p66 and p51 subunits as a single polypeptide with RNase H activityRoberto Zuniga
Programa de Virologia, Instituto de Ciencias Biomedicas, Facultad de Medicina, Universidad de Chile, Independencia 1027, Santiago, Chile
Protein Eng Des Sel 17:581-7. 2004..The TCCR construct maintains Mn(2+)-dependent RNase H activity and specifically cleaves the substrate mimicking the tRNA removal required for second-strand transfer reactions...
Mutations at position 184 of human immunodeficiency virus type-1 reverse transcriptase affect virus titer and viral DNA synthesisJohn G Julias
Basic Research Program, SAIC-Frederick, Inc, NCI-Frederick, Frederick, MD 21702-1201, USA
Virology 322:13-21. 2004..The M184T mutation increased the proportion of 2-LTR circle junctions containing a tRNA insertion, suggesting that the mutation affected the RNase H activity of RT...
Enzymatically amplified surface plasmon resonance imaging method using RNase H and RNA microarrays for the ultrasensitive detection of nucleic acidsTerry T Goodrich
Department of Chemistry, University of California-Irvine, Irvine, California 92697, USA
Anal Chem 76:6173-8. 2004..Finally, in a series of kinetics measurements, the initial rate of hydrolysis is shown to depend directly on the surface concentration of DNA-RNA heteroduplexes...
Selective inhibition of HIV-1 reverse transcriptase (HIV-1 RT) RNase H by small RNA hairpins and dumbbellsRami N Hannoush
Department of Chemistry, Otto Maass Chemistry Building, McGill University, 801 Sherbrooke Street West, , , Canada
Chembiochem 5:527-33. 2004..The results described here suggest a noncompetitive binding mechanism, as outlined in the differential inhibitory characteristics of each of the nucleic acid aptamers against the bacterial, human, and viral RNase H homologues...
Inhibition of human immunodeficiency virus type 1 reverse transcriptase, RNase H, and integrase activities by hydroxytropolonesJoël Didierjean
Unité Propre de Recherche 9002 du CNRS conventionnée à l Université Louis Pasteur, IBMC, 15 rue Rene Descartes, 67084 Strasbourg Cedex, France
Antimicrob Agents Chemother 49:4884-94. 2005..However, all tested compounds exhibited cellular toxicity that presently limits their applications...
Interpreting oligonucleotide microarray data to determine RNA secondary structure: application to the 3' end of Bombyx mori R2 RNAShenghua Duan
Department of Chemistry, University of Rochester, Rochester, New York 14627-0216, USA
Biochemistry 45:9819-32. 2006..It should also facilitate the design of antisense and siRNA oligonucleotides...
Specific recognition and cleavage of the plus-strand primer by reverse transcriptaseAngela Atwood-Moore
Section on Eukaryotic Transposable Elements, Laboratory of Gene Regulation and Development, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA
J Virol 79:14863-75. 2005..Thus, our results identify a conserved element in RT that contacts the PPT and is specifically required for PPT removal...
Creation of DNA overhangs by using modified DNA overhang cloning methodWei Li
Laboratory of Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, 530021, People s Republic of China
Appl Microbiol Biotechnol 75:703-9. 2007..The creation of DNA overhangs by using complementary DNA oligonucleotides, T4 ligase, and RNase H is simpler and cheaper than that by using reverse transcriptase and RNase H...
Effects of donor and acceptor RNA structures on the mechanism of strand transfer by HIV-1 reverse transcriptaseMark Nils Hanson
Department of Biochemistry and Biophysics, University of Rochester Medical Center, Rochester, NY 14642, USA
J Mol Biol 353:772-87. 2005..Overall results support that the acceptor structure has a major influence on the efficiency and position of the invasion and terminus transfer steps...
Biochemical characterization and functional complementation of ribonuclease HII and ribonuclease HIII from Chlamydophila pneumoniae AR39Rubing Liang
College of Life Science and Technology, Shanghai Jiaotong University, 800 Dong Chuan Road, Shanghai 200240, China
Microbiology 153:787-93. 2007..coli RNase H, perhaps representing a more primordial type. This is believed to be the first in vivo functional study of Chlamydophila RNase Hs and the results should contribute to the analysis of RNase Hs of other parasite species...
Mutations in human immunodeficiency virus type 1 RNase H primer grip enhance 3'-azido-3'-deoxythymidine resistanceKrista A Delviks Frankenberry
HIV Drug Resistance Program, National Cancer Institute at Frederick, Frederick, Maryland 21702, USA
J Virol 81:6837-45. 2007....
Characterization of the polymerase and RNase H activities of human foamy virus reverse transcriptasePaul L Boyer
HIV Drug Resistance Program, National Cancer Institute-FCRDC, P.O. Box B, Building 539, Room 130A, Frederick, MD 21702-1201, USA
J Virol 78:6112-21. 2004..Although the sequence of the basic loop of FV RT is different from the basic loop of either Moloney leukemia virus RNase H or Escherichia coli RNase H, the FV RT basic loop appears to have a similar function...
Selection of mutations in the connection and RNase H domains of human immunodeficiency virus type 1 reverse transcriptase that increase resistance to 3'-azido-3'-dideoxythymidineJessica H Brehm
University of Pittsburgh School of Medicine, S818 Scaife Hall, 3550 Terrace Street, Pittsburgh, PA 15261, USA
J Virol 81:7852-9. 2007....
Acceptor RNA cleavage profile supports an invasion mechanism for HIV-1 minus strand transferYan Chen
Department of Biochemistry and Biophysics, University of Rochester Medical Center, New York 14642, USA
J Biol Chem 280:14443-52. 2005..Observations with this new approach lend additional support to the proposed multistep transfer mechanism...
Single-stranded DNA aptamer RT1t49 inhibits RT polymerase and RNase H functions of HIV type 1, HIV type 2, and SIVCPZ RTsJay D Kissel
Department of Biology, Indiana University, Bloomington, Indiana 47405, USA
AIDS Res Hum Retroviruses 23:699-708. 2007..This is the first demonstration of universal inhibition of HIV and SIV(cpz) RTs by a nucleic acid aptamer and supports previous reports suggesting that resistance to RT1t49 may be exceptionally infrequent...
Evidence that HIV-1 reverse transcriptase employs the DNA 3' end-directed primary/secondary RNase H cleavage mechanism during synthesis and strand transferVandana Purohit
Department of Biochemistry and Biophysics, University of Rochester School of Medicine and Dentistry, Rochester, New York 14642, USA
J Biol Chem 280:40534-43. 2005..Overall, results indicate RT can catalyze pause-associated DNA 3' end-directed primary and secondary cuts during synthesis and these cuts can contribute to strand transfer by creation of an invasion site...
DNA polymerization by the reverse transcriptase of the human L1 retrotransposon on its own template in vitroOlga Piskareva
Institute of Biochemistry and Physiology of Microorganisms RAS Pushchino, Prosoekt Nauki 5, 142290 Pushchino, Moscow Region, Russia
FEBS Lett 580:661-8. 2006..A mechanism facilitating minus-strand DNA synthesis during reverse transcription of L1 element in vivo is discussed...
Interaction of the Ty3 reverse transcriptase thumb subdomain with template-primerArkadiusz Bibillo
Reverse Transcriptase Biochemistry Section, Resistance Mechanisms Laboratory, HIV Drug Resistance Program, NCI, Frederick, National Institutes of Health, Frederick, Maryland 21702-1201, USA
J Biol Chem 280:30282-90. 2005..Mutations in the thumb subdomain of Ty3 also affected RNase H activity, suggesting a closer spatial relationship between its N- and C-terminal catalytic centers compared with HIV-1 RT...
Selection of optimal antisense accessible sites of survivin and its application in treatment of gastric cancerQiang Song Tong
Department of Surgery, Union Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province, China
World J Gastroenterol 11:634-40. 2005..To select the optimal antisense accessible sites of survivin, a highly expressed gene in tumor tissues, in order to explore a novel approach to improve biological therapy of gastric cancer...
Forced selection of a human immunodeficiency virus type 1 variant that uses a non-self tRNA primer for reverse transcription: involvement of viral RNA sequences and the reverse transcriptase enzymeTruus E M Abbink
Department of Human Retrovirology, Academic Medical Center, University of Amsterdam, Meibergdreef 15, 1105 AZ Amsterdam, The Netherlands
J Virol 78:10706-14. 2004..We demonstrate that both the PAS and RT mutations improve the replication capacity of the tRNA(1,2)(Lys)-using virus...
Synthesis, physicochemical and biochemical studies of 1',2'-oxetane constrained adenosine and guanosine modified oligonucleotides, and their comparison with those of the corresponding cytidine and thymidine analoguesPushpangadan I Pradeepkumar
Contribution from the Department of Bioorganic Chemistry, Box 581, Biomedical Center, University of Uppsala, S-75123 Uppsala, Sweden
J Am Chem Soc 126:11484-99. 2004....
The HIV-1 reverse transcriptase mutants G190S and G190A, which confer resistance to non-nucleoside reverse transcriptase inhibitors, demonstrate reductions in RNase H activity and DNA synthesis from tRNA(Lys, 3) that correlate with reductions in replicatiJ Wang
Department of Medicine, University of Rochester School of Medicine and Dentistry, NY 14642, USA
Virology 348:462-74. 2006..It also suggests that high concentrations of efavirenz are unlikely to favor the selection of G190S clinically...
Reduced dNTP interaction of human immunodeficiency virus type 1 reverse transcriptase promotes strand transferDarwin J Operario
Departments of Microbiology and Immunology, University of Rochester Medical Center, 601 Elmwood Avenue, Rochester, NY 14642, USA
J Biol Chem 281:32113-21. 2006..Rather, kinetic interference leading to stalled DNA synthesis likely enhanced transfers. These results suggest that the RT-dNTP substrate interaction mechanistically influences strand transfer and recombination of HIV-1 RT...
Highly selective action of triphosphate metabolite of 4'-ethynyl D4T: a novel anti-HIV compound against HIV-1 RTGuangwei Yang
Department of Pharmacology, School of Medicine, Yale University, 333 Cedar Street, New Haven, CT 06520, USA
Antiviral Res 73:185-91. 2007..4'-Ed4TTP showed much less inhibitory effects toward major host DNA polymerases. Overall, our results suggest that 4'-Ed4TTP is the active form for anti-HIV-1 activity via its inhibitory effect against RT...
Facilitating RNA structure prediction with microarraysElzbieta Kierzek
Institute of Bioorganic Chemistry, Polish Academy of Sciences, Noskowskiego 12 14, 61 704 Poznan, Poland
Biochemistry 45:581-93. 2006..The results suggest that probing RNA with oligonucleotide microarrays can facilitate determination of secondary structure...
Insights into the multiple roles of pausing in HIV-1 reverse transcriptase-promoted strand transfersLu Gao
Department of Biochemistry and Biophysics, University of Rochester, New York 14642, USA
J Biol Chem 282:6222-31. 2007..We interpret the new results to mean that pause sites can also serve to stall DNA synthesis, allowing acceptor invasions initiated earlier in the template to catch up with the primer terminus...
Differential susceptibility of HIV-1 reverse transcriptase to inhibition by RNA aptamers in enzymatic reactions monitoring specific steps during genome replicationDaniel M Held
Department of Biology, Indiana University, Bloomington, Indiana 47405, USA
J Biol Chem 281:25712-22. 2006..Together, these results support a model wherein aptamers suppress viral replication by cumulative inhibition of RT at every stage of genome replication...
Combining mutations in HIV-1 reverse transcriptase with mutations in the HIV-1 polypurine tract affects RNase H cleavages involved in PPT utilizationMary Jane McWilliams
HIV Drug Resistance Program, NCI-Frederick, MD 21702-1201, USA
Virology 348:378-88. 2006..In contrast, the mutations in the PPT (alone) and RT (alone) affect the specificity of PPT cleavage but have much less effect on the overall rate of cleavage...
Short partially double-stranded oligodeoxynucleotide induces reverse transcriptase/RNase H-mediated cleavage of HIV RNA and contributes to abrogation of infectivity of virionsAlexey A Matskevich
Institute of Medical Virology, University of Zurich, CH-8006 Zurich, Switzerland
AIDS Res Hum Retroviruses 22:1220-30. 2006..The pretreatment with ODN A strongly reduced the infectivity of virions in cell culture in the absence of any DNA carriers or detergents...
Analysis of mutations made during active synthesis or extension of mismatched substrates further define the mechanism of HIV-RT mutagenesisGwyneth R Liesch
Department of Cell Biology and Molecular Genetics (CBMG, University of Maryland-College Park, College Park, Maryland 20742, USA
Biochemistry 42:5925-36. 2003..This is in contrast to RTs that must bind to then extend mismatches. The importance of these findings with respect to the mechanism of mutagenesis is discussed...
Cooperative regulation for Okazaki fragment processing by RNase HII and FEN-1 purified from a hyperthermophilic archaeon, Pyrococcus furiosusAsako Sato
Institute for Advanced Biosciences, Keio University, Tsuruoka, Yamagata, Japan
Biochem Biophys Res Commun 309:247-52. 2003..It is likely that Pf-RNase HII and Pf-FEN-1 cooperatively process Okazaki fragment during lagging-strand DNA replication...
Antisense oligonuclotides with oxetane-constrained cytidine enhance heteroduplex stability, and elicit satisfactory RNase H response as well as showing improved resistance to both exo and endonucleasesPushpangadan I Pradeepkumar
Department of Bioorganic Chemistry, Biomedical Center, University of Uppsala, Box 581, S-751 23 Uppsala, Sweden
Org Biomol Chem 1:81-92. 2003....
Comparative study of DNA enzymes and ribozymes against the same full-length messenger RNA of the vanilloid receptor subtype IJens Kurreck
Free University Berlin, Institute of Biochemistry, Thielallee 63, 14195 Berlin, Germany
J Biol Chem 277:7099-107. 2002..We therefore conclude that DNA enzymes are an inexpensive, very stable and active alternative to ribozymes for the specific cleavage of long RNA molecules...
Efficient Hsp90-independent in vitro activation by Hsc70 and Hsp40 of duck hepatitis B virus reverse transcriptase, an assumed Hsp90 client proteinJürgen Beck
Department of Internal Medicine II Molecular Biology, University Hospital Freiburg, Hugstetter Strasse 55, Freiburg D 79106, Germany
J Biol Chem 278:36128-38. 2003..Thus Hsc70, mostly known for its role in general protein folding, is able to effect activation of a highly specialized target protein...
Mutations in the RNase H domain of HIV-1 reverse transcriptase affect the initiation of DNA synthesis and the specificity of RNase H cleavage in vivoJohn G Julias
HIV Drug Resistance Program, National Cancer Institute, National Institutes of Health, P.O. Box B, Frederick, MD 21702-1201, USA
Proc Natl Acad Sci U S A 99:9515-20. 2002..Analysis of two-long-terminal repeat circle junctions showed that mutations in the RNase H domain affect the specificity of RNase H cleavage...
Crosslinking of 4.5S RNA to the Escherichia coli ribosome in the presence or absence of the protein FfhJutta Rinke-Appel
Max Planck Institut fur Molekulare Genetik, Berlin, Germany
RNA 8:612-25. 2002..5S molecule, and this was docked onto the ribosome using the crosslinking data. The results are discussed in terms of multiple functions and binding sites of the 4.5S RNA...
Strand transfer occurs in retroviruses by a pause-initiated two-step mechanismRicardo H Roda
Department of Biochemistry and Biophysics, University of Rochester Medical Center, Rochester, New York 14642, USA
J Biol Chem 277:46900-11. 2002..Nucleocapsid protein (NC) is known to influence primer elongation and strand exchange. The presence of NC increased the efficiency of transfers but did not appear to alter the fundamental transfer mechanism...
Mechanism of minus strand strong stop transfer in HIV-1 reverse transcriptionYan Chen
Department of Biochemistry and Biophysics, University of Rochester, New York 14642, USA
J Biol Chem 278:8006-17. 2003..The acceptor invades at gaps created by reverse transcriptase-RNase H in the donor-cDNA hybrid. The fragmented donor is eventually strand-displaced by the acceptor, completing the transfer...
Targeting degradation of RNA by RNase H using DNA hairpinsJing Li
School of Biology, Georgia Institute of Technology, Atlanta, Georgia 30332-0230, USA
Biochemistry 42:10945-54. 2003..The in vitro results indicate that DNA hairpins can enhance the stringency of RNase H targeted degradation of the RNA sites...
Cleavage of a DNA-RNA-DNA/DNA chimeric substrate containing a single ribonucleotide at the DNA-RNA junction with prokaryotic RNases HIIMitsuru Haruki
Department of Material and Life Science, Graduate School of Engineering, Osaka University, 2-1, Yamadaoka, Suita, Osaka, Japan
FEBS Lett 531:204-8. 2002..subtilis RNase HIII did not cleave the chimeric substrate containing a single ribonucleotide. These results suggest that bacterial and archaeal RNases HII are involved in excision of a single ribonucleotide misincorporated into DNA...
Structural basis for the unusual properties of 2',5' nucleic acids and their complexes with RNA and DNAB J Premraj
Department of Crystallography and Biophysics, University of Madras, Guindy Campus, Chennai 600 025, India
Biophys Chem 95:253-72. 2002....
RNA branching and debranching in the yeast retrovirus-like element Ty1Zhi Cheng
School of Biological Sciences, University of Missouri Kansas City, Kansas City, MO 64110, USA
Science 303:240-3. 2004..The properties of the lariat suggest it forms by a novel mechanism and that branching and debranching may play roles in Ty1 reverse transcription at the minus-strand transfer step...
Evolutionary dynamics and population control during in vitro selection and amplification with multiple targetsHua Shi
RNA 8:1461-70. 2002..Additionally, it can be used to isolate a full spectrum of aptamers in a sequential and exhaustive manner for all the different targets in a mixture...
NMR structure of an alpha-L-LNA:RNA hybrid: structural implications for RNase H recognitionJakob T Nielsen
Nucleic Acid Center, Department of Chemistry, University of Southern Denmark, 5230 Odense M, Denmark
Nucleic Acids Res 31:5858-67. 2003..We attempt to rationalise this impaired enzyme activity from the rearrangement of the sugar-phosphate backbone of the alpha-L-LNA:RNA hybrid...
Dynamic NMR structures of [Rp]- and [Sp]-phosphorothioated DNA-RNA hybrids: is flexibility required for RNase H recognition?Marco Tonelli
Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, California 94143 2280 USA
Biophys J 85:2525-38. 2003..These observations, together with the analysis of the crystal structure of a hybrid duplex in complex with ribonuclease H (RNase H), suggested that this flexibility may be required for recognition by RNase H...
Inhibition of aminoglycoside 6'-N-acetyltransferase type Ib-mediated amikacin resistance by antisense oligodeoxynucleotidesRenee Sarno
Department of Biological Science, College of Natural Science and Mathematics, California State University Fullerton, Fullerton, California 92834-6850, USA
Antimicrob Agents Chemother 47:3296-304. 2003..Our results indicate that use of antisense compounds could be a viable strategy to preserve the efficacies of existing antibiotics to which bacteria are becoming increasingly resistant...
Extension and cleavage of the polypurine tract plus-strand primer by Ty1 reverse transcriptaseFrançois Xavier Wilhelm
Institut de Biologie Moleculaire et Cellulaire, 15, rue R Descartes, 67084 Strasbourg, France
J Biol Chem 278:47678-84. 2003....
The ribonuclease H activity of the reverse transcriptases of human immunodeficiency viruses type 1 and type 2 is modulated by residue 294 of the small subunitZ Sevilya
Department of Cell Biology and Histology, Sackler School of Medicine, Tel Aviv University, Tel Aviv 69978, Israel
Nucleic Acids Res 31:1481-7. 2003..A comparative in vitro study of the kinetic parameters of the RNase H activity suggests that residue 294 affects the K(m) rather than the kcat value, influencing the affinity for the RNA.DNA substrate...
Oligonucleotide enhanced cytotoxicity of Idarubicin for lymphoma cellsJ G Sharp
J G Sharp Department of Cell Biology and Anatomy, University of Nebraska Medical Center, 986395 Nebraska Medical Center, Omaha, NE 68198 6395, USA
Leuk Lymphoma 42:417-27. 2001..This approach offers new opportunities for purging of lymphoma cells from hematopoietic harvests and systemic lymphoma therapy...
Multiple mechanisms for initiation of ColE1 DNA replication: DNA synthesis in the presence and absence of ribonuclease HS DasGupta
Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland 20892
Cell 51:1113-22. 1987..Lagging strand synthesis terminates 17 nucleotides upstream of the normal replication origin, forcing unidirectional replication...
Transcriptional activation of ColE1 DNA synthesis by displacement of the nontranscribed strandH Masukata
Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland 20892
Cell 51:1123-30. 1987..The necessary length for the single-stranded region is at least 40 nucleotides. The region probably provides a site for initial binding of a helicase that further unwinds the template DNA for initiation of DNA synthesis...
Regulators of serine/threonine protein phosphatases at the dawn of a clinical era?R E Honkanen
Department of Biochemistry and Molecular Biology, College of Medicine, University of South Alabama, Mobile, AL 36688, USA
Curr Med Chem 9:2055-75. 2002....
Circular transcripts of the testis-determining gene Sry in adult mouse testisB Capel
Laboratory of Eukaryotic Molecular Genetics, Medical Research Council, National Institute for Medical Research, London, England
Cell 73:1019-30. 1993..We suggest that the circles arise from normal splicing processes as a consequence of the unusual genomic structure surrounding the Sry locus in the mouse...
Role of cysteine residues in ribonuclease H from Escherichia coli. Site-directed mutagenesis and chemical modificationS Kanaya
Protein Engineering Research Institute, Osaka, Japan
Biochem J 271:59-66. 1990..Thus the sensitivity of E. coli RNAase H to N-ethylmaleimide arises not from blocking of the thiol group but from steric hindrance by the modifying group incorporated at either Cys-13 or Cys-133...
Translation of cyclin mRNA is necessary for extracts of activated xenopus eggs to enter mitosisJ Minshull
Department of Biochemistry, University of Cambridge, England
Cell 56:947-56. 1989..The extracts can enter mitosis if either of the cyclin mRNAs is left intact. We conclude that the synthesis of these cyclins is necessary for mitotic cell cycles in cleaving Xenopus embryos...
Crystal structure of the moloney murine leukemia virus RNase H domainDavid Lim
Integrated Program in Cellular, Molecular and Biophysical Studies, College of Physicians and Surgeons, Columbia University, New York, New York 10032, USA
J Virol 80:8379-89. 2006..coli, and HIV-1 revealed that a loop of the HIV-1 connection domain resides within the same region of the Mo-MLV and E. coli C-helix. The HIV-1 connection domain may serve to recognize and bind the RNA/DNA substrate major groove...
Insertion of a small peptide of six amino acids into the beta7-beta8 loop of the p51 subunit of HIV-1 reverse transcriptase perturbs the heterodimer and affects its activitiesPradeep K Pandey
Department of Biochemistry and Molecular Biology, University of Medicine and Dentistry of New Jersey, New Jersey Medical School, 185 South Orange Avenue, Newark, NJ 07103, USA
BMC Biochem 3:18. 2002....
The identification of spermine binding sites in 16S rRNA allows interpretation of the spermine effect on ribosomal 30S subunit functionsIoannis Amarantos
Laboratory of Biochemistry and Laboratory of Biology, School of Medicine, University of Patras, GR 26500 Patras, Greece
Nucleic Acids Res 30:2832-43. 2002..The above can be interpreted in terms of conformational changes in 16S rRNA, induced by the incorporation of ABA-spermine...
Role of integrase in reverse transcription of the Saccharomyces cerevisiae retrotransposon Ty1M Wilhelm
Institut de Biologie Moleculaire et Cellulaire, 15 rue Rene Descartes, 67084 Strasbourg, France
Eukaryot Cell 4:1057-65. 2005..We suggest that interaction between these acidic amino acid residues of IN and a basic region of RT could be critical for the correct folding of RT and for the formation of an active conformation of the enzyme...
Mg2+ dependency of HIV-1 reverse transcription, inhibition by nucleoside analogues and resistanceValerie Goldschmidt
Unité Propre de Recherche 9002 du CNRS conventionnée à l Université Louis Pasteur, IBMC, 15 rue Rene Descartes, 67084 Strasbourg Cedex, France
Nucleic Acids Res 34:42-52. 2006..Thus, differences in the free Mg2+ concentration between different cell types or during the cell cycle might strongly affect HIV-1 replication and its inhibition...
Solution structure of DNA/RNA hybrid duplex with C8-propynyl 2'-deoxyadenosine modifications: Implication of RNase H and DNA/RNA duplex interactionHunjoong Lee
Department of Chemistry, University of Houston, 136 Fleming Building, Houston, TX 77204 5003, USA
Biochim Biophys Acta 1769:20-8. 2007....
Research Grants
- FUNCTIONAL ANALYSIS OF AN RNA STRUCTURAL MOTIFYa Ming Hou; Fiscal Year: 2005..coli CysRS for its ability to distinguish cysteine from serine. These studies shall shed new light on the molecular interactions responsible for the accurate translation of the genetic code. ..
- Stem Cell Quality Assays: Correlation with Aging/HealthJOHN GRAHAM SHARP; Fiscal Year: 2010..This research will validate laboratory assays of stem cell compartment quality which can then be applied to clinical situations and may reveal blood cytokine assays with surrogate predictive value. ..
- Maintenance of the tRNA 3' endYa Ming Hou; Fiscal Year: 2007..Christine Chow and Dr. Ming-Daw Tsai. PHS 398 (Rev. 5/95) (Form Page 4) Page 2 EE Number pages consecutivelyat the bottom throughout the application. Do not use suffixes such as 3a, 3b. ..
- HIV RNase H natural product inhibitorsMICHAEL PARNIAK; Fiscal Year: 2007..The research program will have significant impact on public health by developing new anti-HIV therapeutics for use in the treatment of patients infected with HIV strains resistant to the current clinically used drugs. ..
- Genetic conflict shapes centromeres and heterochromatinHARMIT MALIK; Fiscal Year: 2007....
- Genetic conflict shapes centromeres and heterochromatinHarmit S Malik; Fiscal Year: 2010....
- FUNCTIONS OF tRNA MODIFICATIONSYa Ming Hou; Fiscal Year: 2009..abstract_text> ..
- FUNCTIONS OF tRNA MODIFICATIONSYa Ming Hou; Fiscal Year: 2010..Information to be gained from this proposal will provide important insights to build a solid foundation for selective inhibition of the bacterial enzyme so as to improve human health care. ..
- Role of Tetraspan Glycoproteins (CD63) in HIV ReplicationMONIQUE REGAIL FERGUSON; Fiscal Year: 2010....
- GnRH signaling in LbetaT2 gonadotrope cellsNicholas Webster; Fiscal Year: 2009..These genetic models will include cell-specific transgenic overexpression of selected co-repressors as well as gonadotrope-specific deletion of components of the Gs and Gq/11 pathways using cre-loxP technology. ..
- FUNCTIONS OF tRNA MODIFICATIONSYa Ming Hou; Fiscal Year: 2009..Information to be gained from this proposal will provide important insights to build a solid foundation for selective inhibition of the bacterial enzyme so as to improve human health care. ..
- A Link between RNAi and Fragile X Mental RetardationScott Hammond; Fiscal Year: 2009..While this project focuses on FMRP regulation of neuronal genes, it will provide a general framework for studies on all aspects of RNAi regulation of mammalian cellular pathways. ..
- Genetic conflict shapes centromeres and heterochromatinHARMIT MALIK; Fiscal Year: 2009....
- Mappicine inhibitors of HIV Ribonuclease HMICHAEL PARNIAK; Fiscal Year: 2003..abstract_text> ..
- FUNCTIONAL ANALYSIS OF AN RNA STRUCTURAL MOTIFYa Ming Hou; Fiscal Year: 2001..The results of these studies will be integrated into structural studies of tRNACys and its complex with cysteine-tRNA synthetase in order to have a better understanding of tRNA structural recognition by an aminoacyl-tRNA synthetase. ..
- Stable suppression of gene function in mammals by RNAiScott Hammond; Fiscal Year: 2002..proposed commercial application: not available ..
- Aminoacyl-tRNA synthetases in ArchaeaYa Ming Hou; Fiscal Year: 2006..jannaschii to gain a broader insight into its aminoacyl-tRNA synthetases as a basis for understanding the origin and evolution of contemporary mRNA-encoded protein synthesis in extant organisms. ..
- Maintenance of the tRNA 3' endYa Ming Hou; Fiscal Year: 2007..Because of the importance of CCA in maintenance of cellular life, the proposed studies will have a strong impact on human health and diseases. ..
- A Bioinformatic Approach to Inferring Protein ContactsMARCELLA MCCLURE; Fiscal Year: 2005..Several experimental laboratories have agreed to test the residue contact predictions resulting from these studies for Ebola, VSV and measles. ..
- Rational Design of HIV Entry InhibitorsMONIQUE FERGUSON; Fiscal Year: 2005..Since our peptides will be targeting viral structures, we expect them to have low toxicity, and no cross-resistance with the current antiretroviral drugs. ..
- Combinatorial Approaches to Activators of the NGF Recep*Nicholas Webster; Fiscal Year: 2005..The Specific Aim of this proposal is to screen the combinatorial asterriquinone library against the NGF receptor. ..
