Dependent Deoxyribonucleic Acid Research Articles

Synthesis and antitumor activity of fused quinoline derivatives.

Some tetracyclic quinolines (9 and 14) with a [2-methoxy-4-[(methylsulfonyl)amino]phenyl]amino side chain were prepared and their deoxyribonucleic acid (DNA) intercalative properties, KB cytotoxicity, antitumor activity (P388 leukemia), and ability to induce topoisomerase II dependent DNA cleavage were investigated. The indoloquinoline derivative 9 exhibited the most potent activity (dose = 6.3 mg, T/C% = 300) in this series. The steric structural features of the chromophores of the compounds previously and newly synthesized were studied by a computer-associated molecular graphics technique. Relationships between the steric structural features of the chromophores and biological activities are also discussed.

Deoxyribonucleic acid polymerase from the marine Pseudomonas sp. BAL-31.

A deoxyribonucleic acid (DNA)-dependent DNA polymerase (DNA nucleotidyltransferase) was purified 3,000-fold from the marine Pseuodomonas sp. BAL-31. The molecular weight of the native enzyme was estimated by glycerol gradient sedimentation to be 110,000. The enzyme migrated in sodium dodecyl sulfate-acrylamide gels as a single polypeptide with a molecular weight of 105,000. An absolute requirement for divalent cation was satisfied by Mg2+ or Mn2+ at concentrations of 1 mM. Monovalent cations at concentrations higher than 50 mM showed an inhibitory effect. The polymerase activity was resistant to N-ethylmaleimide and showed a wide pH optimum.

Processive nature of reverse transcription by avian myeloblastosis virus deoxyribonucleic acid polymerase.

The ribonucleic acid dependent deoxyribonucleic acid polymerase from avian myeloblastosis virus was shown to synthesize poly(dT) transcripts by a processive mechanism using poly(rA)1100.oligo(dT)12-18 as template and primer. Template challenge experiments demonstrate that at low temperature and ionic strength, the polymerase remains bound to the completed template-daughter strand complex after completion of daughter strand elongation. Higher temperatures and ionic strength increase the dissociation of the enzyme from the complex, thus reducing transcript length. Analysis of product size and quantity indicates that the degree of processivity is also influenced by the types and concentrations of metal ions present and indicates that the metal ions affect the activity of the poly(rA) as a template more than they affect processivity or enzyme activity. The results also lead to the conclusion that initiation is the rate-limiting step under all of our experimental conditions. The arguments for a processive as opposed to distributive mechanism are based on an analysis of enzyme-template interactions, product size, and amount of product made under specific reaction conditions.

Ribonucleic acid dependent deoxyribonucleic acid synthesis by Escherichia coli deoxyribonucleic acid polymerase. I. Characterization of the polymerization reaction.

Ribonucleic acid dependent deoxyribonucleic acid synthesis by Escherichia coli deoxyribonucleic acid polymerase. I. Characterization of the polymerization reaction.

Inactivation of Herpes Simplex Virus by Thiosemicarbazones and Certain Cations

We demonstrated that herpes simplex virus types 1 and 2, including a type 2 strain which transforms hamster cells in vitro, and Herpesvirus saimiri are inactivated by exposure to thiosemicarbazones. Because thiosemicarbazones are thought to interact with heavy metals in this inactivation process (9), we tested and found some of these herpesviruses to be susceptible to exposure to certain heavy metals. A virion polymerase was sought because the ribonucleic acid (RNA)-dependent deoxyribonucleic acid (DNA) polymerase of Rous sarcoma virus and the DNA-dependent RNA polymerase of vaccinia virus are inhibited. However, neither DNA nor RNA polymerase activity could be demonstrated in herpes simplex virions. The ability of thiosemicarbazone to ameliorate the course of herpes simplex virus infection in rabbit eyes was observed, but was considered insufficient to be of clinical importance.

A new deoxyribonucleic acid dependent deoxyribonucleic acid polymerase from HeLa cell mitochondria.

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTNew deoxyribonucleic acid dependent deoxyribonucleic acid polymerase from HeLa cell mitochondriaMichael Fry and Arthur WeissbachCite this: Biochemistry 1973, 12, 19, 3602–3608Publication Date (Print):September 1, 1973Publication History Published online1 May 2002Published inissue 1 September 1973https://doi.org/10.1021/bi00743a005RIGHTS & PERMISSIONSArticle Views23Altmetric-Citations47LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (870 KB) Get e-Alerts Get e-Alerts

Characteristics of deoxyribonucleic acid polymerase isolated from spores of Rhizopus stolonifer.

Deoxyribonucleic acid (DNA)-dependent DNA polymerase was purified several hundredfold from germinated and ungerminated spores of the fungus Rhizopus stolonifer. The partially purified enzymes from both spore stages exhibited identical characteristics; incorporation of [(3)H]deoxythymidine monophosphate into DNA required Mg(2+), DNA, a reducing agent, and the simultaneous presence of deoxyguanosine triphosphate, deoxycytidine triphosphate, and deoxyadenosine triphosphate. Heat-denatured and activated DNAs were better templates than were native DNAs. The buoyant density of the radioactive product of the reaction was similar to that of the template DNA. The enzyme is probably composed of a single polypeptide chain with an S value of 5.12 and an estimated molecular weight of 70,000 to 75,000. During the early stages of purification, the enzyme fraction from ungerminated spores required exogenous DNA for maximum activity, whereas the corresponding enzyme fraction from germinated spores did not require added DNA. Apparently DNA polymerase from germinated spores was more tightly bound to endogenous DNA than was the enzyme from ungerminated spores.

Inhibitory effect of streptonigrin on a murine sarcoma virus-induced tumor cell line (MSC) and selection of drug-resistant clones.

A cell line, MSC, chronically infected with the MSV-M sarcoma-leukemia virus complex, was exposed to the ribonucleic acid (RNA)-dependent deoxyribonucleic acid polymerase inhibitor streptonigrin (SN). Replication of cells was inhibited by nanogram concentrations of the drug. Some resistant cells were isolated and passed in the presence of SN. The retention of resistance was dependent on continuous presence of the inhibitor. Virus production by the resistant cells was reduced, but not eliminated. Furthermore, the drug inhibited RNA synthesis in secondary mouse embryo fibroblasts, but not in the MSC cells.

Deoxyribonucleic acid polymerase activities in normal and leukovirus-infected chicken embryo cells.

Chicken embryo cells normally contain, in addition to deoxyribonucleic acid (DNA)-dependent DNA (D-DNA) polymerases, a novel "R-DNA-polymerase" which specifically copies polyriboadenylic acid strands. This R-DNA polymerase cannot copy natural ribonucleic acid or polyribocytidylic acid strands to a significant extent. Infection of cells with the leukovirus RAV-2 leads to the intracellular formation of large amounts of the viral RNA-dependent DNA polymerase whose properties differ from the cell R-DNA polymerase. Chicken cells transformed by a Rous sarcoma virus mutant which produce noninfectious alpha-type Rous sarcoma virus (f), a leukovirus known to be deficient in the viral RNA-dependent DNA polymerase, do not contain detectable viral RNA-dependent DNA polymerase, whereas the cellular R-DNA polymerase is found in normal amounts. There seems to be no relationship between the cellular R-DNA polymerase and the RNA-dependent DNA polymerase of the avian leukoviruses.

Properties of Maedi Nucleic Acid and the Presence of Ribonucleic Acid- and Deoxyribonucleic Acid-Dependent Deoxyribonucleic Acid Polymerase in the Virions

Maedi virus contains a ribonucleic acid (RNA) which can be resolved into three major components, namely, 62S, 33S, and 13S, by sucrose gradient centrifugation. The presence of RNA- and deoxyribonucleic acid (DNA)-dependent DNA polymerase in virions of maedi virus was demonstrated. The enzyme product could be converted into acid-soluble form by pancreatic deoxyribonuclease, but was resistant to digestion by pancreatic ribonuclease and to hydrolysis by NaOH.

Surface-active agents for isolation of the core component of avian myeloblastosis virus.

Sixty-one surface-active agents were evaluated in a procedure designed to assess their ability to remove the envelope from the core component of avian myeloblastosis virus (AMV). The procedure consisted of centrifugation of intact AMV through a series of sucrose gradients each containing an upper layer of agent at one of eight concentrations between 0.01 and 10%. The effectiveness of an agent in producing AMV cores was indicated by (i) the appearance of light-scattering bands in the region of core buoyant density in gradient tubes; (ii) the range of surfactant concentration over which these bands appeared; and (iii) an electron microscopy assessment by the negative-staining technique of the relative proportion of core to non-core material in each of these bands. Six nonionic surfactants were selected by this screening method for comparison in regard to recovery of core protein and endogenous ribonucleic acid (RNA)-dependent deoxyribonucleic acid (DNA) polymerase activity, as well as further morphologic evaluation by electron microscopy. The nonionic surfactants of the polyoxyethylene alcohol class (particularly, Sterox SL) were most effective. Nonionic surfactants of the polyoxyethylene alkylphenol class (particularly, Nonidet P-40) were also effective. Sterox SL and Nonidet P-40 each gave a more than fivefold increase in specific activity of endogenous RNA-dependent DNA polymerase, and each gave a low recovery of core protein. Sterox SL did not interfere to the extent that Nonidet P-40 did in procedures which involved spectrophotometric assay at 260 nm. The use of Sterox SL resulted in the least envelope contamination of core preparations by electron microscopy examination, the most recovery of protein and endogenous RNA-dependent DNA polymerase activity, and a core buoyant density in sucrose of 1.27 g/ml.

Deficiency of viral ribonucleic acid-dependent deoxyribonucleic acid polymerase in noninfectious virus-like particles released from murine sarcoma virus-transformed hamster cells.

Virions from hamster cells transformed by a new strain of murine sarcoma virus (MSV) appear to represent a form of MSV deficient in one or more of the viral components necessary for infectivity. Both the noninfectious virions and the sarcoma virus-transformed cells, which have no detectable replicating leukemia helper virus of either murine or hamster origin, are deficient in viral-type ribonucleic acid (RNA)-dependent deoxyribonucleic acid (DNA) polymerase activity (i.e., reverse transcriptase activity stimulated by the synthetic RNA-DNA template polyribo-adenylic-oligodeoxythymidylic acid). In comparison, both murine leukemia virus (MuLV) and MuLV-infected cells have abundant viral-type reverse transcriptase activity. It appears, therefore, that the leukemia virus genome may be required for the production of infectious sarcoma virus by contributing information needed for the full expression of functional viral-type reverse transcriptase.

Specific inhibition of mammalian ribonucleic acid C-type virus deoxyribonucleic acid polymerases by rat antisera.

Inhibition of the ribonucleic acid (RNA)- and deoxyribonucleic acid (DNA)-dependent DNA polymerase activities of mammalian C-type viruses was obtained with sera from rats bearing murine leukemia virus-induced transplant tumors. Polymerase activities of nonmammalian (viper) C-type virus and murine mammary tumor virus were not inhibited by such sera nor by serum from a rat immunized with the DNA polymerase of feline leukemia virus purified by isoelectric focusing. The latter serum appeared to inhibit preferentially the DNA-dependent DNA polymerase activity of mammalian C-type viruses showing no inhibition of RNA-dependent DNA synthesis.

Deoxyribonucleic acid polymerase(s) of Rous sarcoma virus: effects of virion-associated endonuclease on the enzymatic product.

Purified preparations of Rous sarcoma virus (RSV) contain ribonuclease which is either a constituent of the virion surface or an adsorbed contaminant. Treatment of the virus with nonionic detergent to activate ribonucleic acid (RNA)-dependent deoxyribonucleic acid (DNA) polymerase renders the viral genome susceptible to hydrolysis by the external ribonuclease. The extent of this susceptibility can be substantially reduced by the use of limited amounts of detergent. At a concentration of detergent which provides a maximum initial rate of DNA synthesis, the degradation of endogenous viral RNA results in a reduced yield of high molecular weight DNA: RNA hybrid from the polymerase reaction. Attempts to detect virion-associated deoxyribonuclease, by using a variety of double helical DNA species as substrates, have been unsuccessful, but small amounts of nuclease activity directed against single-stranded DNA may be present in purified virus.

Transformation of murine cells by two "slow viruses," visna virus and progressive pneumonia virus.

Visna and progressive pneumonia virus (PPV), two antigenically related, non-oncogenic "slow viruses" which have ribonucleic acid (RNA)-dependent deoxyribonucleic acid (DNA) polymerase activity, were examined for their ability to transform cells. Murine cells which had been exposed to either visna or PPV developed foci of altered, spindle-shaped cells 3 to 4 weeks after infection. Visna and PPV transformed lines were established from these cultures. There was no evidence that other oncogenic DNA or RNA viruses were involved in the observed transformation. Visna or PPV could be "rescued" from all transformed lines by co-cultivation with normal sheep testis cells. "Rescued" virus was identified as visna or PPV, and they retained the capacity to transform mouse cells. These experiments may have important implications in the understanding of both viral carcinogenesis and "slow" viral infections.