| Third and Final Technical Report for F49620-92-0232-DEF (San Francisco State University) |
29 APR 95 |
137 pages |
| Authors:
Ernest Kun; SAN FRANCISCO STATE UNIV TIBURON CA ROMBERG TIBURON CENTERS
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 | Cellular proteins extracted from normal and cancer cells bind POLY(ADP-ribose) polymerase on nitro-cellulose membrane transblots. Histones at 1 rng/ml concentration completely prevent the binding of poly(ADP-ribose) polymerase to cellular proteins, indicating that the binding of histones to poly(ADP-ribose) polymerase sites competitively blocks the association of poly (ADP-ribose) polymerase to proteins other than histones. The direct binding of poly(ADP-ribos polymerase to histones is shown by crosslinking with glutaraldehyde. The C-terminal basic ... |
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| Progress Report for Grant F49620-92-J-0232 (San Francisco State University) |
08 APR 94 |
74 pages |
| Authors:
Ernest Kun; SAN FRANCISCO STATE UNIV TIBURON CA ROMBERG TIBURON CENTERS
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| Intracellular phosphorylation of poly (ADP-ribose) polymerase was assayed in streptolysin-0-permeabilized human lymphocytes. Whereas 32P incorporation from (gamma-32P)ATP into immuno-precipitated enzyme protein was undetectable in resting cells, significant phosphorylation of this enzyme was observed in lymphocytes treated with phytohemagglutinin. The phosphorylation of poly (ADP-ribose) polymerase in permeabilized cells was not stimulated by phorbol ester, but phosphorylation of other proteins and of a specific oligopeptide substrate of protein kinase C was increased ... |
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| Inhibition of DNA Binding by the Phosphorylation of Poly ADP-Ribose Polymerase Protein Catalyzed by Protein Kinase C |
21 APR 93 |
50 pages |
| Authors:
Ernest Kun; SAN FRANCISCO STATE UNIV TIBURON CA ROMBERG TIBURON CENTERS
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| Purified type II (beta) and type III (alpha) protein kinase C phosphorylates highly purified polyADP-ribose polymerase in vitro whereby 2 mols of phosphate are transferred from ATP to serine and threonine. |
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| Molecular Toxicology of Chromatin |
JAN 92 |
94 pages |
| Authors:
Ernest Kun; SAN FRANCISCO STATE UNIV TIBURON CA TIBURON CENTER FOR ENVIRONMENTAL STUDIES
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| The binding of the ADP unlimited ribosyl transferase protein and its polypeptide components, obtained by digestion with plasmin, to histone-Sepharose 4B matrices was determined by a centrifugation technique. Both the intact enzyme protein and the 29 kDa terminal polypeptide bound to histone affinity matrices in a strictly DNA-dependent manner. Whereas the nature of covalently matrix- bound histones had no apparent specificity towards the enzyme protein or its polypeptide components, among ... |
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| Molecular Toxicology of Chromatin |
04 JUL 89 |
17 pages |
| Authors:
Ernest Kun; SAN FRANCISCO STATE UNIV TIBURON CA TIBURON CENTER FOR ENVIRONMENTAL STUDIES
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| During the tenure of this grant period, extending previous studies, a novel physiological regulatory function of a specific DNA binding nuclear protein, ADPRT, has been uncovered, which can explain its cell physiological role as a gene regulator by way of topological modification of DNA structure. The relevance of this approach to the general theme of chromatin toxicology consists in the fact that subtle cellular responses to environmental and genetic factors ... |
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| Molecular Cloning of the Bovine Liver ADPRT cDNA |
13 DEC 88 |
13 pages |
| Authors:
Srinivas S. Sastry; Eva Kirsten; Ernest Kun; CALIFORNIA UNIV SAN FRANCISCO
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| A cDNA probe was prepared from a calf liver library, identified by synthetic polynucleotide probes and cloned into lambda gt 11 vector. Its hybridization with mRNA of calf liver identified a 4 kb mRNA. Keywords: Molecular biology, Amino acids. (aw) |
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| Molecular Toxicology of Chromatin |
31 DEC 87 |
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| Authors:
Ernest Kun; CALIFORNIA UNIV SAN FRANCISCO CARDIOVASCULAR RESEARCH INST
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 | Part I. Benzamide-DNA Interactions; Deductions from Binding, Enzyme- Kinetics and from X-ray Structural Analysis of a 9-Ethyladenine-Benzamide Adduct: The interaction of benzamide with the isolated components of calf thymus poly(ADP-ribose) polymerase and with liver nuclei has been investigated. Part II. Molecular Interactions Between DNA, Poly(ADP-Ribose) Polymerase and Histones: Molecular interactions between purified poly(ADP-ribose) polymerase, whole thymus histones, histone H1, rat fibroblast genomic DNA, and closed circular and linearized SV40 DNA ... |
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| Molecular Cloning of Adenosinediphosphoribosyl Transferase |
08 SEP 87 |
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| Authors:
Ernest Kun; CALIFORNIA UNIV SAN FRANCISCO
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| The purpose of obtaining the gene of Adenosinediphosphoribosyl Transferase (ADPRT) is: 1) the complete amino acid sequence of this large protein is best determined from the DNA sequence of the gene, 2) isolation of the gene provides gene probes that permit location and quantitation of the gene within genomic DNA, and 3) a variety of biological experiments at the cellular level requires specific gene probes. The DNA-associating enzyme, adenosinediphosphoribosyl transferase, ... |
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| Cloning of the poly(ADP-ribose) Gene from Rat Liver |
24 SEP 86 |
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| Authors:
Ernest Kun; CALIFORNIA UNIV SAN FRANCISCO
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| Inhibition of the nuclear enzyme poly (ADP-ribose) polymerase by substances that interfere with the DNA binding of the enzyme molecule profoundly inhibit cellular phenotypic changes (malignant transformation) induced either by non-toxic doses of ultimate carcinogens and more recently in an oncogene construct-containing cell line by steroid hormones. Enzyme inhibition in ontogenically stable cells had no measurable physiological effect as tested by cell growth or viability, thus the biological role of ... |
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| Molecular Toxicology of Chromatin: The Role of Poly (ADP-Ribose) in Gene Control |
15 DEC 85 |
118 pages |
| Authors:
Ernest Kun; CALIFORNIA UNIV SAN FRANCISCO CARDIOVASCULAR RESEARCH INST
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| This research endeavor approaches 'chromatin toxicity' in a selective manner. Environmental factors (both physical and chemical) exert a subtle long- term effect on cellular systems, that is distinguishable from the acute lethal effects of toxins or high doses of radiation. We focus our attention on the effect of 'low-dose' toxicology which affects cellular behavior and alters cellular phenotype. Present concepts define the molecular basis of cellular phenotype as a carefully ... |
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| Construction of New Potential Reactivators of Phosphonylated Acetylcholinesterase. Substitution of F for H in the Nucleus of Pyridinecarboxaldehyde Oximes |
NOV 83 |
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| Authors:
Jerome McLick; Ernest Kun; CALIFORNIA UNIV SAN FRANCISCO CARDIOVASCULAR RESEARCH INST
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| Two new Fluoro-pyridnecarboxaldehyde oxime methiodide (F-PAM) compounds have been synthesized: 3-F-2-PAM and 5-F-2-PAM. These compounds and their unquaternized oxime precursors have been rigorously characterized by elemental analysis, mass spectroscopy, MNR, UV, and pKa determination. Detail spectroscopic interpretations are provided and correlated with analogous data for other PAM compounds. Both F-isomers of 2-PAM are obtained in low yield, 3-F- 2-PAM is unstable during titration with NaOH, while 5-F-2-PAM is stable but ... |
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| Construction of New Potential Reactivators of Phosphonylated Acetylcholinesterase. Substitution of F for H in the Nucleus of Pyridinecarboxaldehyde Oximes |
NOV 82 |
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| Authors:
Jerome McLick; Ernest Kun; CALIFORNIA UNIV SAN FRANCISCO CARDIOVASCULAR RESEARCH INST
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| Syn-3-Fluoro-4-pyridinecarboxaldehyde oxime methiodide (3-F-4-PAM), a new potential reactivator of phosphonylated acetylcholinesterase, has been synthesized and characterized by classical organic chemical and structural methods. The pKa of 3-F-4-PAM is 8.18, which represents a lowering of the pKa value of 4-PAM (pKa 8.6) by 0.4 pKa units, due to the electron-withdrawing effect of the F atom. The pKa value of 3-F-4-M equals that of the potent reactivator TMB-4, and thus the reactivator ... |
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| Molecular Toxicology of Chromatin |
SEP 1982 |
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| Authors:
Ernest Kun; CALIFORNIA UNIV SAN FRANCISCO DEPT OF PHARMACOLOGY
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| The patho-biological function of the nuclear homopolymer; poly ADP- ribose is being studied. It was found that this homopolymer, that has been identified recently by us to be a unique nucleic acid, with helical conformation, and is covalently bound to prevalently non histone chromatin proteins, exhibits specific quantitative signals during aging differentiation and precancerous perturbations. (Author) |
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| Regulation of Chromatin Function by Polyadenosine Diphosphoribosylation |
07 JUN 1982 |
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| Authors:
Ernest Kun; Takeyoshi Minaga; Eva Kirsten; George Jackowski; Leonard Peller; CALIFORNIA UNIV SAN FRANCISCO
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| The biological function of poly (ADP-R) based on its macromolecular properties is envisaged as a nucleic acid component of a cross linking system capable of promoting or inhibiting the regulatory effect of chromatin proteins on transcription. Two examples, the action of triiodothyronine and of chemical carcinogens illustrate this complex action of the homopolymer functioning as a protein modifier. Although DNA and RNA can be profitably studied in isolated systems without ... |
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| Development of an Assay for the Early Detection of Organ Specific Carcinogenesis by the Determination and Turnover of NAD(+) and Polyadenosine Diphosphoribose |
28 OCT 80 |
88 pages |
| Authors:
Ernest Kun; CALIFORNIA UNIV SAN FRANCISCO
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| A hypothesis was proposed that predicts the possibility of developing a specific biochemical methodology capable of detecting early and specific signals in chromatin proteins that precede cellular toxicity or malignant transformation, caused by toxic agents or by other environmental factors (e.g., radiation). This long-range aim has been approached the identification of covalent modification of chromatin proteins by a specific enzymatic process of ADP-ribosylations and poly (ADP)-ribosylation to be the most ... |
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