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  • Mutation  (43)
  • American Association for the Advancement of Science (AAAS)  (43)
  • American Chemical Society (ACS)
  • PANGAEA
  • 1985-1989  (43)
  • 1987  (43)
Collection
Publisher
  • American Association for the Advancement of Science (AAAS)  (43)
  • American Chemical Society (ACS)
  • PANGAEA
  • Springer  (8)
Years
  • 1985-1989  (43)
Year
  • 1
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1987-05-01
    Description: A fundamental problem in chemistry and biochemistry is understanding the role of solvation in determining molecular properties. Recent advances in statistical mechanical theory and molecular dynamics methodology can be used to solve this problem with the aid of supercomputers. By using these advances the free energies of solvation of all the chemical classes of amino acid side chains, four nucleic acid bases and other organic molecules can be calculated. The effect of a site-specific mutation on the stability of trypsin is predicted. The results are in good agreement with available experiments.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bash, P A -- Singh, U C -- Langridge, R -- Kollman, P A -- CA-25644/CA/NCI NIH HHS/ -- GM-29072/GM/NIGMS NIH HHS/ -- RR-1081/RR/NCRR NIH HHS/ -- New York, N.Y. -- Science. 1987 May 1;236(4801):564-8.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/3576184" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acids ; Chemistry, Physical ; *Computer Simulation ; Hydrogen Bonding ; Models, Chemical ; Mutation ; Physicochemical Phenomena ; Purines ; Pyrimidines ; Solvents ; *Thermodynamics
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  • 2
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1987-12-04
    Description: The relatively nonspecific single-stranded deoxyribonuclease, staphylococcal nuclease, was selectively fused to an oligonucleotide binding site of defined sequence to generate a hybrid enzyme. A cysteine was substituted for Lys116 in the enzyme by oligonucleotide-directed mutagenesis and coupled to an oligonucleotide that contained a 3'-thiol. The resulting hybrid enzyme cleaved single-stranded DNA at sites adjacent to the oligonucleotide binding site.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Corey, D R -- Schultz, P G -- New York, N.Y. -- Science. 1987 Dec 4;238(4832):1401-3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Chemistry, University of California, Berkeley 94720.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/3685986" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Base Sequence ; DNA, Single-Stranded/metabolism ; Hydrolysis ; Micrococcal Nuclease/*genetics/metabolism ; Models, Molecular ; Mutation ; Protein Conformation ; Staphylococcus aureus/enzymology/genetics ; Substrate Specificity
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  • 3
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1987-06-05
    Description: The body plan of Drosophila is determined to a large extent by homeotic genes, which specify the identity and spatial arrangement of the body segments. Homeotic genes share a characteristic DNA segment, the homeo box, which encodes a defined domain of the homeotic proteins. The homeo domain seems to mediate the binding to specific DNA sequences, whereby the homeotic proteins exert a gene regulatory function. By isolating the normal Antennapedia gene, fusing its protein-coding sequences to an inducible promoter, and reintroducing this fusion gene into the germline of flies, it has been possible to transform head structures into thoracic structures and to alter the body plan in a predicted way. Sequence homologies suggest that similar genetic mechanisms may control development in higher organisms.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gehring, W J -- New York, N.Y. -- Science. 1987 Jun 5;236(4806):1245-52.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2884726" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Base Sequence ; Blastoderm/ultrastructure ; Drosophila/embryology/*genetics ; Embryonic and Fetal Development ; *Genes, Homeobox ; Mutation ; Ovum/ultrastructure
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  • 4
    Publication Date: 1987-09-11
    Description: The envelope of the human immunodeficiency virus type 1 (HIV-1) plays a central role in the process of virus entry into the host cell and in the cytopathicity of the virus for lymphocytes bearing the CD4 molecule. Mutations that affect the ability of the envelope glycoprotein to form syncytia in CD4+ cells can be divided into five groups: those that decrease the binding of the envelope protein to the CD4 molecule, those that prevent a post-binding fusion reaction, those that disrupt the anchorage of the envelope glycoprotein in the membrane, those that affect the association of the two subunits of the envelope glycoprotein, and those that affect post-translational proteolytic processing of the envelope precursor protein. These findings provide a functional model of the HIV envelope glycoprotein.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kowalski, M -- Potz, J -- Basiripour, L -- Dorfman, T -- Goh, W C -- Terwilliger, E -- Dayton, A -- Rosen, C -- Haseltine, W -- Sodroski, J -- AI24755/AI/NIAID NIH HHS/ -- CA40658/CA/NCI NIH HHS/ -- CA40659/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 1987 Sep 11;237(4820):1351-5.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/3629244" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Genes ; Genes, Viral ; Glycoproteins/analysis/*genetics ; HIV/*genetics ; Mutation ; Phenotype ; Plasmids ; Viral Envelope Proteins/analysis/*genetics
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  • 5
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1987-09-18
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Marx, J L -- New York, N.Y. -- Science. 1987 Sep 18;237(4821):1415.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/3114880" target="_blank"〉PubMed〈/a〉
    Keywords: Bacillus thuringiensis/genetics ; *Containment of Biohazards ; *DNA, Recombinant ; Fungi/genetics ; Mutation ; Pseudomonas/genetics ; Pseudomonas fluorescens/genetics ; Rhizobium/genetics ; United States ; United States Environmental Protection Agency
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  • 6
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1987-03-13
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Marrack, P -- New York, N.Y. -- Science. 1987 Mar 13;235(4794):1311-3.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2435000" target="_blank"〉PubMed〈/a〉
    Keywords: Antigens/*immunology ; B-Lymphocytes/immunology ; Epitopes/immunology ; HLA Antigens/immunology ; HLA-DR Antigens/immunology ; Immunoglobulins/genetics/immunology ; Mutation ; Receptors, Antigen, T-Cell/genetics/immunology ; T-Lymphocytes/immunology
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  • 7
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1987-12-18
    Description: The principles of pattern formation in embryogenesis can be studied in Drosophila by means of a powerful combination of genetic and transplantation experiments. The segmented pattern of the Drosophila embryo is organized by two activities localized at the anterior and posterior egg poles. Both activities exert inducing and polarizing effects on the pattern when transplanted to other egg regions. A small set of maternal genes have been identified that are required for these activities. Mutants in these genes lack either the anterior or posterior part of the segmented pattern. The unsegmented terminal embryonic regions require a third class of genes and form independently of the anterior and posterior centers.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Nusslein-Volhard, C -- Frohnhofer, H G -- Lehmann, R -- New York, N.Y. -- Science. 1987 Dec 18;238(4834):1675-81.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Max-Planck-Institut fur Entwicklungsbiologie, Tubingen, Federal Republic of Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/3686007" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Drosophila/cytology/*embryology/genetics ; Embryo, Nonmammalian/cytology/physiology ; Genes ; Mutation ; Phenotype
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  • 8
    Publication Date: 1987-08-14
    Description: On the basis of electrophysiological analysis of Shaker mutants, the Shaker locus of Drosophila melanogaster has been proposed to encode a structural component of a voltage-dependent potassium channel, the A channel. Unlike sodium channels, acetylcholine receptors, and calcium channels, K+ channels have not been purified biochemically. To facilitate biochemical studies of a K+ channel, genomic DNA from the Shaker locus has been cloned. Rearrangements in five Shaker mutants have been mapped to a 60-kilobase segment of the genome. Four complementary DNA clones have been analyzed. These clones indicate that the Shaker gene contains multiple exons distributed over at least 65 kilobases of genomic DNA in the region where the mutations mapped. Furthermore, the gene may produce several classes of alternatively spliced transcripts. Two of the complementary DNA clones have been sequenced and their sequences support the hypothesis that Shaker encodes a component of a K+ channel.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Papazian, D M -- Schwarz, T L -- Tempel, B L -- Jan, Y N -- Jan, L Y -- NS15963/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 1987 Aug 14;237(4816):749-53.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2441470" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Base Sequence ; Cloning, Molecular ; DNA/*genetics/isolation & purification ; Drosophila melanogaster/*genetics ; Exons ; *Ion Channels ; Membrane Proteins/*genetics ; Mutation ; Nucleic Acid Hybridization ; Potassium/*metabolism ; RNA Splicing ; Transcription, Genetic ; Translocation, Genetic
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  • 9
    Publication Date: 1987-01-30
    Description: Isochromosomal, respiratory-deficient yeast strains, such as a mit-, a hypersuppressive petite, and a petite lacking mitochondrial DNA, are phenotypically identical in spite of differences in their mitochondrial genomes. Subtractive hybridizations of complementary DNA's to polyadenylated RNA isolated from derepressed cultures of these strains reveal the presence of nuclear-encoded transcripts whose abundance varies not only between them and their respiratory-competent parent, but among the respiratory-deficient strains themselves. Transcripts of some nuclear-encoded mitochondrial proteins, like cytochrome c and the alpha and beta subunits of the mitochondrial adenosine triphosphatase, whose abundance is affected by glucose or heme, do not vary. In the absence of major metabolic variables, yeast cells seem to respond to the quality and quantity of mitochondrial DNA and modulate the levels of nuclear-encoded RNA's, perhaps as a means of intergenomic regulation.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Parikh, V S -- Morgan, M M -- Scott, R -- Clements, L S -- Butow, R A -- New York, N.Y. -- Science. 1987 Jan 30;235(4788):576-80.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/3027892" target="_blank"〉PubMed〈/a〉
    Keywords: Base Sequence ; Cell Nucleus/physiology ; Cytochrome c Group/genetics ; DNA, Fungal/genetics ; DNA, Mitochondrial/genetics ; Electron Transport Complex IV/genetics ; Gene Expression Regulation ; Genes, Fungal ; Genotype ; Mitochondria/*physiology ; Mutation ; RNA, Fungal/genetics ; RNA, Messenger/genetics ; RNA, Ribosomal/genetics ; Saccharomyces cerevisiae/*genetics
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  • 10
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1987-02-27
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Racker, E -- New York, N.Y. -- Science. 1987 Feb 27;235(4792):959-61.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2434995" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Bacteria/metabolism ; Cloning, Molecular ; Crystallization ; Humans ; Ion Channels/physiology ; Membrane Proteins/genetics/*physiology ; Mitochondria/metabolism ; Mutation ; Protein Conformation ; Receptors, Cell Surface/physiology
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  • 11
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1987-11-20
    Description: The repertoire of antibody variable (V) regions has been subject to evolutionary selection, affecting both the diversity of V region genes in the germline and their expression in the B lymphocyte population and its subsets. In ontogeny, contact with an antigen leads to the expansion of B cells expressing antibodies complementary to it. In a defined phase of B cell differentiation, new sets of V regions are generated from the existing repertoire through somatic hypermutation. Cells carrying advantageous antibody mutants are selected into the memory compartment and produce a stable secondary response upon reexposure to the antigen.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Rajewsky, K -- Forster, I -- Cumano, A -- New York, N.Y. -- Science. 1987 Nov 20;238(4830):1088-94.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute for Genetics, University of Cologne, Koln, FRG.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/3317826" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antibodies/*genetics ; *Antibody Diversity ; B-Lymphocytes/*physiology ; *Biological Evolution ; *Genes, Immunoglobulin ; Genes, Switch ; Immunity ; Immunoglobulin Isotypes/genetics ; Immunoglobulin Variable Region/genetics ; Mice ; Mutation ; Selection, Genetic
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  • 12
    Publication Date: 1987-09-11
    Description: The validity of mouse liver tumor end points in assessing the potential hazards of chemical exposure to humans is a controversial but important issue, since liver neoplasia in mice is the most frequent tumor target tissue end point in 2-year carcinogenicity studies. The ability to distinguish between promotion of background tumors versus a genotoxic mechanism of tumor initiation by chemical treatment would aid in the interpretation of rodent carcinogenesis data. Activated oncogenes in chemically induced and spontaneously occurring mouse liver tumors were examined and compared as one approach to determine the mechanism by which chemical treatment caused an increased incidence of mouse liver tumors. Data suggest that furan and furfural caused an increased incidence in mouse liver tumors at least in part by induction of novel weakly activating point mutations in ras genes even though both chemicals did not induce mutations in Salmonella assays. In addition to ras oncogenes, two activated raf genes and four non-ras transforming genes were detected. The B6C3F1 mouse liver may thus provide a sensitive assay system to detect various classes of proto-oncogenes that are susceptible to activation by carcinogenic insult. As illustrated with mouse liver tumors, analysis of activated oncogenes in spontaneously occurring and chemically induced rodent tumors will provide information at a molecular level to aid in the use of rodent carcinogenesis data for risk assessment.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Reynolds, S H -- Stowers, S J -- Patterson, R M -- Maronpot, R R -- Aaronson, S A -- Anderson, M W -- New York, N.Y. -- Science. 1987 Sep 11;237(4820):1309-16.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/3629242" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Line ; *Cell Transformation, Neoplastic ; Cells, Cultured ; Liver Neoplasms/*genetics ; Mice ; Mutation ; Nucleic Acid Hybridization ; *Oncogenes ; *Proto-Oncogenes ; Risk
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  • 13
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1987-02-13
    Description: A general mechanism for the splicing of nuclear messenger RNA precursors in eukaryotic cells has been widely accepted. This mechanism, which generates lariat RNAs possessing a branch site, seems related to the RNA-catalyzed reactions of self-splicing introns. The splicing of nuclear messenger RNA precursors involves the formation of a multicomponent complex, the spliceosome. This splicing body contains at least three different small nuclear ribonucleoprotein particles (snRNPs), U2, U5, and U4 + U6. A complex containing precursor RNA and the U2 snRNP particle is a likely intermediate in the formation of the spliceosome.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sharp, P A -- CA14051/CA/NCI NIH HHS/ -- GM34277/GM/NIGMS NIH HHS/ -- P01-CA42063/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 1987 Feb 13;235(4790):766-71.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/3544217" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Base Sequence ; Introns ; Mutation ; Nucleic Acid Precursors/*genetics ; Protein Biosynthesis ; RNA Precursors ; *RNA Splicing ; RNA, Catalytic ; RNA, Messenger/*genetics ; RNA, Ribosomal/genetics ; RNA, Small Nuclear/genetics ; Saccharomyces cerevisiae/genetics ; Tetrahymena/genetics
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  • 14
    Publication Date: 1987-05-29
    Description: Whole-cell and single-channel voltage-clamp techniques were used to identify and characterize the channels underlying the fast transient potassium current (A current) in cultured myotubes and neurons of Drosophila. The myotube (A1) and neuronal (A2) channels are distinct, differing in conductance, voltage dependence, and gating kinetics. The myotube currents have a faster and more voltage-dependent macroscopic inactivation rate, a larger steady-state component, and a less negative steady-state inactivation curve than the neuronal currents. The myotube channels have a conductance of 12 to 16 picosiemens, whereas the neuronal channels have a conductance of 5 to 8 picosiemens. In addition, the myotube channel is affected by Shaker mutations, whereas the neuronal channel is not. Together, these data suggest that the two channels are separate molecular structures, the expression of which is controlled, at least in part, by different genes.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Solc, C K -- Zagotta, W N -- Aldrich, R W -- NS 07158-07/NS/NINDS NIH HHS/ -- NS23294/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 1987 May 29;236(4805):1094-8.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2437657" target="_blank"〉PubMed〈/a〉
    Keywords: Drosophila/*genetics/metabolism ; Electrophysiology ; Ion Channels/*metabolism ; Muscles/metabolism ; Mutation ; Neurons/metabolism ; Potassium/*metabolism
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  • 15
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1987-05-29
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Solomon, F -- New York, N.Y. -- Science. 1987 May 29;236(4805):1043-4.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/3554513" target="_blank"〉PubMed〈/a〉
    Keywords: Dictyostelium/genetics ; Muscles/physiology ; Mutation ; Myosins/genetics/*physiology ; Phenotype ; Saccharomyces cerevisiae
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  • 16
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1987-06-05
    Description: Recombinant DNA procedures have now been applied to the problem of the identification of molecular defects in man that account for heritable diseases, somatic mutations associated with neoplasia, and acquired infectious disease. Thus recombinant DNA technology has rapidly expanded our ability to diagnose disease. Substantial advances in the simplification of procedures for diagnostic purposes have been made, and the informed physician has gained in diagnostic accuracy as a consequence of these developments. The wide application of recombinant DNA diagnostics will depend on simplicity, speed of results, and cost containment.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Caskey, C T -- DK31428/DK/NIDDK NIH HHS/ -- New York, N.Y. -- Science. 1987 Jun 5;236(4806):1223-9.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/3296189" target="_blank"〉PubMed〈/a〉
    Keywords: Alleles ; Base Sequence ; *DNA, Recombinant ; Forensic Medicine/methods ; Genetic Diseases, Inborn/*diagnosis ; Genetic Linkage ; *Genetic Techniques ; Humans ; Infection/*diagnosis ; Mutation ; Neoplasms/*genetics
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  • 17
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1987-12-11
    Description: Messenger RNA's are translated in successive three-nucleotide steps (a reading frame), therefore decoding must proceed in only one of three possible frames. A molecular model for correct propagation of the frame is presented based on (i) the measured translational properties of transfer RNA's (tRNA's) that contain an extra nucleotide in the anticodon loop and (ii) a straightforward concept about anticodon loop structure. The model explains the high accuracy of reading frame maintenance by normal tRNA's, as well as activities of all characterized frameshift suppressor tRNA's that have altered anticodon loops.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Curran, J F -- Yarus, M -- GM30881/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1987 Dec 11;238(4833):1545-50.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder 80309.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/3685992" target="_blank"〉PubMed〈/a〉
    Keywords: Anticodon/*genetics ; Base Sequence ; Codon ; Mutation ; Nucleic Acid Conformation ; Protein Biosynthesis ; RNA, Messenger/genetics ; RNA, Transfer/*genetics
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  • 18
    Publication Date: 1987-05-01
    Description: Neoplastic transformation has been associated with a variety of structural changes in cell surface carbohydrates, most notably increased sialylation and beta 1-6-linked branching of complex-type asparagine (Asn)-linked oligosaccharides (that is, -GlcNAc beta 1-6Man alpha 1-6Man beta 1-). However, little is known about the relevant glycoproteins or how these transformation-related changes in oligosaccharide biosynthesis may affect the malignant phenotype. Here it is reported that a cell surface glycoprotein, gp 130, is a major target of increased beta 1-6-linked branching and that the expression of these oligosaccharide structures is directly related to the metastatic potential of the cells. Glycosylation mutants of a metastatic tumor cell line were selected that are deficient in both beta 1-6 GlcNAc transferase V activity and metastatic potential in situ. Moreover, induction of increased beta 1-6 branching in clones of a nonmetastatic murine mammary carcinoma correlated strongly with acquisition of metastatic potential. The results indicate that increased beta 1-6-linked branching of complex-type oligosaccharides on gp 130 may be an important feature of tumor progression related to increased metastatic potential.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Dennis, J W -- Laferte, S -- Waghorne, C -- Breitman, M L -- Kerbel, R S -- R0I-CA41233/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 1987 May 1;236(4801):582-5.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2953071" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Asparagine ; Carbohydrate Conformation ; Cell Line ; Cell Transformation, Neoplastic ; Glucosyltransferases/metabolism ; Glycosylation ; Lysosome-Associated Membrane Glycoproteins ; *Membrane Glycoproteins ; Membrane Proteins/metabolism ; Mice ; Mutation ; *N-Acetylglucosaminyltransferases ; *Neoplasm Metastasis ; Neoplasms, Experimental/genetics/metabolism ; *Oligosaccharides/biosynthesis ; Structure-Activity Relationship
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  • 19
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1987-09-25
    Description: The aspartate receptor of Escherichia coli and Salmonella typhimurium is a cell surface sensory transducer that binds extracellular aspartate and sends a transmembrane signal to the inside of the bacterium. The flexibility and allostery of this receptor was examined by placing sulfhydryl groups as potential cross-linking sites at targeted locations in the protein. Seven different mutant receptors were constructed, each containing a single cysteine residue at a different position in the primary structure. Intramolecular disulfide bond formation within oligomers of these mutant receptors is shown to trap structural fluctuations and to detect ligand-induced changes in structure. The results indicate that the receptor oligomer has a flexible, dynamic structure which undergoes a global change upon aspartate binding.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Falke, J J -- Koshland, D E Jr -- New York, N.Y. -- Science. 1987 Sep 25;237(4822):1596-600.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2820061" target="_blank"〉PubMed〈/a〉
    Keywords: Allosteric Regulation ; Bacterial Proteins/*physiology ; *Chemotaxis ; Cloning, Molecular ; Cysteine ; Disulfides ; Macromolecular Substances ; Membrane Proteins/*physiology ; Mutation ; Protein Conformation ; *Receptors, Amino Acid ; Receptors, Neurotransmitter/*physiology ; Structure-Activity Relationship
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  • 20
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1987-10-09
    Description: Evidence from many sources shows that the control of gene expression in higher organisms is related to the methylation of cytosine in DNA, and that the pattern of methylation is inherited. Loss of methylation, which can result from DNA damage, will lead to heritable abnormalities in gene expression, and these may be important in oncogenesis and aging. Transformed permanent lines often lose gene activity through de novo methylation. It is proposed that epigenetic defects in germline cells due to loss of methylation can be repaired by recombination at meiosis but that some are transmitted to offspring.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Holliday, R -- New York, N.Y. -- Science. 1987 Oct 9;238(4824):163-70.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Genetics Division, National Institute for Medical Research, Mill Hill, London, United Kingdom.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/3310230" target="_blank"〉PubMed〈/a〉
    Keywords: Aging ; Animals ; DNA/*genetics ; DNA Repair ; Genetic Diseases, Inborn/*genetics ; Humans ; Meiosis ; Methylation ; Mutation
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  • 21
    Publication Date: 1987-04-24
    Description: A recently developed assay for somatic cell mutations was used to study survivors of the atomic bomb at Hiroshima. This assay measures the frequency of variant erythrocytes produced by erythroid precursor cells with mutations that result in a loss of gene expression at the polymorphic glycophorin A (GPA) locus. Significant linear relations between variant frequency (VF) and radiation exposure were observed for three different variant cell phenotypes. The spontaneous and induced VFs agree with previous measurements of radiation-induced mutagenesis in other systems; this evidence supports a mutational origin for variant cells characterized by a loss of GPA expression and suggests that the GPA assay system may provide a cumulative dosimeter of past radiation exposures. VFs for some survivors differ dramatically from the calculated dose response, and these deviations appear to result primarily from statistical fluctuations in the number of mutations in the stem-cell pool. These fluctuations allow one to estimate the number of long-lived hemopoietic stem cells in humans.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Langlois, R G -- Bigbee, W L -- Kyoizumi, S -- Nakamura, N -- Bean, M A -- Akiyama, M -- Jensen, R H -- New York, N.Y. -- Science. 1987 Apr 24;236(4800):445-8.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/3563520" target="_blank"〉PubMed〈/a〉
    Keywords: Antibodies, Monoclonal ; Dose-Response Relationship, Radiation ; Flow Cytometry ; Gene Frequency ; Glycophorin/*genetics/immunology ; Humans ; MNSs Blood-Group System/*genetics ; Mutation ; *Nuclear Warfare ; Sialoglycoproteins/*genetics
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  • 22
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1987-08-07
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Marx, J L -- New York, N.Y. -- Science. 1987 Aug 7;237(4815):602-3.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/3603042" target="_blank"〉PubMed〈/a〉
    Keywords: Cell Transformation, Neoplastic ; Colonic Neoplasms/genetics ; Fibroblast Growth Factors/genetics ; Gene Expression Regulation ; Humans ; Mutation ; *Oncogenes ; Proto-Oncogenes ; Sarcoma, Kaposi/genetics
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  • 23
    Publication Date: 1987-04-24
    Description: Transcriptional enhancement is a general mechanism for regulation of gene expression in which particular proteins bound to specific DNA sequences stimulate the efficiency of initiation from linked promoters. One such protein, the glucocorticoid receptor, mediates enhancement in a glucocorticoid hormone-dependent manner. In this study, a region of the 795-amino acid rat glucocorticoid receptor that is active in transcriptional enhancement was identified. The active region was defined by expressing various receptor deletion mutants in stably and transiently transfected cells and examining the regulated transcription of hormone-responsive genes. Mutant receptors lacking as many as 439 amino-terminal amino acids retained activity, as did those with as many as 270 carboxyl-terminal amino acids deleted. This suggests that the 86-amino acid segment between the most extensive terminal deletions, which also includes sequences required for specific DNA binding in vitro, is sufficient for enhancer activation. In fact, a 150-amino acid receptor fragment that encompasses this segment mediates constitutive enhancement.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Miesfeld, R -- Godowski, P J -- Maler, B A -- Yamamoto, K R -- New York, N.Y. -- Science. 1987 Apr 24;236(4800):423-7.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/3563519" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; DNA-Binding Proteins/*genetics ; *Enhancer Elements, Genetic ; *Genes, Regulator ; Mutation ; Rats ; Receptors, Glucocorticoid/*genetics ; Structure-Activity Relationship ; Transfection
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  • 24
    Publication Date: 1987-08-14
    Description: Potassium currents are crucial for the repolarization of electrically excitable membranes, a role that makes potassium channels a target for physiological modifications that alter synaptic efficacy. The Shaker locus of Drosophila is thought to encode a K+ channel. The sequence of two complementary DNA clones from the Shaker locus is reported here. The sequence predicts an integral membrane protein of 70,200 daltons containing seven potential membrane-spanning sequences. In addition, the predicted protein is homologous to the vertebrate sodium channel in a region previously proposed to be involved in the voltage-dependent activation of the Na+ channel. These results support the hypothesis that Shaker encodes a structural component of a voltage-dependent K+ channel and suggest a conserved mechanism for voltage activation.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tempel, B L -- Papazian, D M -- Schwarz, T L -- Jan, Y N -- Jan, L Y -- NS15963/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 1987 Aug 14;237(4816):770-5.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2441471" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Base Sequence ; Codon ; DNA/*genetics ; Drosophila melanogaster/*genetics ; Electrophorus/genetics ; Genes ; *Ion Channels ; Membrane Proteins/*genetics ; Mutation ; Potassium/*metabolism ; Sodium/metabolism
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  • 25
    Publication Date: 1987-03-06
    Description: The yeast Saccharomyces cerevisiae contains two functional homologues of the ras oncogene family, RAS1 and RAS2. These genes are required for growth, and all evidence indicates that this essential function is the activation of adenylate cyclase. In contrast, ras in mammalian cells does not appear to influence adenylate cyclase activity. To clarify the relation between ras function in yeast and in higher eukaryotes, and the role played by yeast RAS in growth control, it is necessary to identify functions acting upstream of RAS in the adenylate cyclase pathway. The evidence presented here indicates that CDC25, identified by conditional cell cycle arrest mutations, encodes such an upstream function.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Robinson, L C -- Gibbs, J B -- Marshall, M S -- Sigal, I S -- Tatchell, K -- CA37702/CA/NCI NIH HHS/ -- GM07229/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1987 Mar 6;235(4793):1218-21.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/3547648" target="_blank"〉PubMed〈/a〉
    Keywords: Adenylyl Cyclases/*metabolism ; Enzyme Activation ; Genes, Dominant ; Haploidy ; Mutation ; *Oncogenes ; Phenotype ; Saccharomyces cerevisiae/enzymology/*genetics/growth & development/physiology ; Spores ; Suppression, Genetic
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  • 26
    Publication Date: 1987-02-06
    Description: The human T-cell leukemia viruses, HTLV-I and HTLV-II, contain a gene, termed x, with transcriptional regulatory function. The properties of the x proteins were analyzed by constructing mutant genes containing site-directed deletions and point mutations. The results demonstrate that the amino terminal 17 amino acids of the x protein constitute part of a functional domain that is critical for the transcriptional activating properties of the protein. Within this region, substitution of a leucine residue for a proline residue results in major changes in the trans-activation phenotype of the protein. The mutant HTLV-II x protein, though incapable of activating the HTLV-II long terminal repeat, will block trans-activation of the HTLV-II long terminal repeat by the wild-type protein. The altered phenotype of this mutant suggests a potential negative regulatory function of the x protein.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wachsman, W -- Cann, A J -- Williams, J L -- Slamon, D J -- Souza, L -- Shah, N P -- Chen, I S -- CA 30388/CA/NCI NIH HHS/ -- CA 32727/CA/NCI NIH HHS/ -- CA 38597/CA/NCI NIH HHS/ -- etc. -- New York, N.Y. -- Science. 1987 Feb 6;235(4789):674-7.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/3027894" target="_blank"〉PubMed〈/a〉
    Keywords: Deltaretrovirus/*genetics ; Gene Expression Regulation ; *Genes, Viral ; Mutation ; Transcription Factors/*genetics ; Transcription, Genetic
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  • 27
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1987-11-13
    Description: Genetic analyses suggested that the opaque-2 (o2) locus in maize acts as a positive, transacting, transcriptional activator of the zein seed storage-protein genes. Because isolation of the gene is requisite to understanding the molecular details of this regulation, transposon mutagenesis with the transposable element suppressor-mutator (Spm) was carried out, and three mutable o2 alleles were obtained. One of these alleles contained an 8.3-kilobase autonomous Spm, another a 6.8-kilobase nonautonomous Spm, and the third an unidentified transposon that is unrelated to Spm. A DNA sequence flanking the autonomous Spm insertion was verified to be o2-specific and provided a probe to clone a wild-type allele. Northern blots indicated that the gene is expressed in wild-type endosperm but not in leaf tissues or in endosperms homozygous for a mutant allele of the O2 gene. A transcript was detected in endosperms homozygous for mutations at opaque-7 and floury-2, an indication that O2 expression is independent of these two other putative regulators of zein synthesis.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Schmidt, R J -- Burr, F A -- Burr, B -- GM31093/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1987 Nov 13;238(4829):960-3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Biology Department, Brookhaven National Laboratory, Upton, NY 11973.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2823388" target="_blank"〉PubMed〈/a〉
    Keywords: Alleles ; Cloning, Molecular ; DNA Restriction Enzymes ; *DNA Transposable Elements ; *Genes, Regulator ; Homozygote ; Mutation ; Nucleic Acid Hybridization ; Plants/*genetics ; Zea mays/genetics
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  • 28
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1987-11-06
    Description: Diversification of the antibody repertoire in mammals results from a series of apparently random somatically propagated gene rearrangement and mutational events. Nevertheless, it is well known that the adult repertoire of antibody specificities is acquired in a developmentally programmed fashion. As previously shown, rearrangement of the gene segments encoding the heavy-chain variable regions (VH) of mouse antibodies is also developmentally ordered: the number of VH gene segments rearranged in B lymphocytes of fetal mice is small but increased progressively after birth. In this report, human fetal B-lineage cells were also shown to rearrange a highly restricted set of VH gene segments. In a sample of heavy-chain transcripts from a 130-day human fetus the most frequently expressed human VH element proved to be closely related to the VH element most frequently expressed in murine fetal B-lineage cells. These observations are important in understanding the development of immunocompetence.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Schroeder, H W Jr -- Hillson, J L -- Perlmutter, R M -- AI07470/AI/NIAID NIH HHS/ -- GM07454/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1987 Nov 6;238(4828):791-3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, University of Washington, Seattle 98195.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/3118465" target="_blank"〉PubMed〈/a〉
    Keywords: Adult ; Amino Acid Sequence ; Animals ; B-Lymphocytes/immunology ; Base Sequence ; Fetus ; *Genes, Immunoglobulin ; Humans ; Immunoglobulin Heavy Chains/genetics ; Immunoglobulin Variable Region/genetics ; Mice ; Molecular Sequence Data ; Mutation ; Sequence Homology, Nucleic Acid
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  • 29
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1987-06-12
    Description: Computer simulations of the diffusion of a substrate to an enzyme active site were performed. They included the detailed shape of the protein and an accurate description of its electrostatic potential. Application of the method to the diffusion of the superoxide anion to the protein superoxide dismutase revealed that the electric field of the enzyme enhances the association rate of the anion by a factor of 30 or more. Calculated changes in the association rate as a function of ionic strength and amino acid modification paralleled the observed behavior. Design principles of superoxide dismutase are considered with respect to insights provided by the simulations. A possible means of enhancing the enzyme turnover rate through site-directed mutagenesis is proposed.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sharp, K -- Fine, R -- Honig, B -- GM30518/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1987 Jun 12;236(4807):1460-3.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/3589666" target="_blank"〉PubMed〈/a〉
    Keywords: *Binding Sites ; *Computer Simulation ; Diffusion ; Enzymes/*metabolism ; Kinetics ; Mathematics ; Mutation ; Superoxide Dismutase/metabolism
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  • 30
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1987-08-21
    Description: Gene expression is dependent on the interaction of DNA binding factors with distinct promoter control elements to activate RNA synthesis. The expression of the HIS4 gene in yeast is under two different control systems. One of these, general amino acid control, involves a DNA binding protein, GCN4, that stimulates transcription in response to amino acid starvation by binding to 5'-TGACTC-3' sequences in the HIS4 promoter region. A second system, the basal level control, stimulates HIS4 transcription in the absence of amino acid starvation. The basal level transcription of the HIS4 gene is under the control of two genes, BAS1 and BAS2, which are also required for the control of purine biosynthesis. In addition, BAS2 is required for the utilization of organic phosphates in the growth medium. Genetic mapping and DNA sequence analysis show that BAS2 is PHO2, a gene previously identified as a regulator of phosphate metabolism. Direct biochemical analysis shows that the BAS2 gene encodes a protein that binds to both the HIS4 and PHO5 promoters. The involvement of a single DNA binding protein in the regulation of histidine, adenine, and phosphate metabolism suggests that yeast may use a few key DNA binding proteins to coordinate the regulation of diverse metabolic pathways.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Arndt, K T -- Styles, C -- Fink, G R -- GM 35010-04/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1987 Aug 21;237(4817):874-80.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/3303332" target="_blank"〉PubMed〈/a〉
    Keywords: Acid Phosphatase/*genetics ; Chromosome Mapping ; Gene Expression Regulation ; Genes, Fungal ; Histidine/*genetics ; Mutation ; Phosphates/physiology ; Promoter Regions, Genetic ; Saccharomyces cerevisiae/*genetics ; Transcription Factors/physiology ; Transcription, Genetic
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  • 31
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1987-06-05
    Description: It is now possible, by site-directed mutagenesis of the gene, to change any amino acid residue in a protein to any other. In enzymology, application of this technique is leading to exciting new insights both into the mechanism of catalysis by particular enzymes, and into the basis of catalysis itself. The precise and often delicate changes that are being made in and near the active sites of enzymes are illuminating the interdependent roles of catalytic groups, and are allowing the first steps to be taken toward the rational alteration of enzyme specificity and reactivity.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Knowles, J R -- New York, N.Y. -- Science. 1987 Jun 5;236(4806):1252-8.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/3296192" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acids/metabolism ; Binding Sites ; Catalysis ; Chemistry, Physical ; Enzyme Stability ; Enzymes/*genetics/metabolism ; Mutation ; Physicochemical Phenomena ; Substrate Specificity ; Thermodynamics
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  • 32
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1987-10-23
    Description: Clathrin-coated membranes and coated vesicles take part in the selective transfer of proteins between different subcellular compartments of eukaryotic cells. To allow assessment of the role of clathrin in vesicular transport, genetic analysis of the clathrin heavy chain gene (CHC1) in Saccharomyces cerevisiae was initiated. The complete heavy chain gene was cloned, and the effects of deletion of this gene were studied. The null mutation (chc1-delta) is lethal unless a suppressor of clathrin deficiency (scd1) is present. Even in the presence of the suppressor gene, mutants lacking the clathrin heavy chain grow slowly, are genetically unstable, are morphologically abnormal, and show loss of or reduction in several yeast functions. These results indicate that clathrin is required for normal growth of yeast, and, therefore, most likely, for growth of all eukaryotic cells.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lemmon, S K -- Jones, E W -- AI06884/AI/NIAID NIH HHS/ -- AM18090/AM/NIADDK NIH HHS/ -- GM29713/GM/NIGMS NIH HHS/ -- etc. -- New York, N.Y. -- Science. 1987 Oct 23;238(4826):504-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biological Sciences, Carnegie Mellon University, Pittsburgh, PA 15213.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/3116672" target="_blank"〉PubMed〈/a〉
    Keywords: Biological Transport ; Clathrin/*genetics/physiology ; Cloning, Molecular ; Coated Pits, Cell-Membrane/physiology ; DNA, Fungal/genetics ; Diploidy ; Immunologic Techniques ; Mutation ; Saccharomyces cerevisiae/*growth & development ; Spores ; Suppression, Genetic
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  • 33
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1987-05-01
    Description: The herpes simplex virus 1 genome consists of one long and one short stretch of unique sequences flanked by inverted repeat sequences. The nucleotide sequence and RNA map predict 12 open reading frames designated as US1 through US12 within the short stretch of unique sequences. This paper reports the construction of virus mutants from which US2, US3, or US4 had been deleted that are capable of growth in cell culture. One of the three deleted genes, US4, specifies the viral envelope glycoprotein G. Mutants with deletions in US1, US8, US9, US10, US11, and US12 have been previously reported. The nine genes deleted from this region form two clusters, US1 through US4 and US8 through US12, and encode at least two and possibly more structural proteins. The presence of so many genes dispensable for growth in cell culture suggests several hypotheses regarding their function and evolution.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Longnecker, R -- Roizman, B -- CA-08494/CA/NCI NIH HHS/ -- CA-19264/CA/NCI NIH HHS/ -- T32 PHS AI 07182/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 1987 May 1;236(4801):573-6.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/3033823" target="_blank"〉PubMed〈/a〉
    Keywords: Base Sequence ; DNA Restriction Enzymes ; DNA, Recombinant ; DNA, Viral/genetics ; *Genes, Viral ; Glycoproteins/genetics ; Mutation ; Plasmids ; Repetitive Sequences, Nucleic Acid ; Simplexvirus/*genetics/growth & development ; Viral Proteins/genetics
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  • 34
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1987-10-23
    Description: M1 RNA, the catalytic RNA subunit of Escherichia coli ribonuclease P, can cleave novel transfer RNA (tRNA) precursors that lack specific domains of the normal tRNA sequence. The smallest tRNA precursor that was cleaved efficiently retained only the domain of the amino acid acceptor stem and the T stem and loop. The importance of the 3' terminal CCA nucleotide residues in the processing of both novel and normal tRNA precursors implies that the same enzymatic function of M1 RNA is involved.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉McClain, W H -- Guerrier-Takada, C -- Altman, S -- AI10257/AI/NIAID NIH HHS/ -- GM19422/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1987 Oct 23;238(4826):527-30.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Bacteriology, University of Wisconsin, Madison 53706.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2443980" target="_blank"〉PubMed〈/a〉
    Keywords: Base Sequence ; DNA/genetics ; DNA, Recombinant ; Endoribonucleases/*metabolism ; Escherichia coli/*enzymology ; *Escherichia coli Proteins ; Molecular Sequence Data ; Mutation ; Nucleic Acid Conformation ; Plasmids ; RNA Precursors/*metabolism ; RNA, Bacterial/genetics ; RNA, Transfer, Amino Acyl/genetics ; Ribonuclease P ; Ribonuclease T1/metabolism ; Structure-Activity Relationship ; Substrate Specificity ; Suppression, Genetic
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  • 35
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1987-10-23
    Description: The role of guanine nucleotides in ras p21 function was determined by using the ability of p21 protein to induce maturation of Xenopus oocytes as a quantitative assay for biological activity. Two oncogenic mutant human N-ras p21 proteins, Asp12 and Val12, actively induced maturation, whereas normal Gly12 p21 was relatively inactive in this assay. Both mutant proteins were found to be associated with guanosine triphosphate (GTP) in vivo. In contrast, Gly12 p21 was predominantly guanosine diphosphate (GDP)-bound because of a dramatic stimulation of Gly12 p21-associated guanosine triphosphatase (GTPase) activity. A cytoplasmic protein was shown to be responsible for this increase in activity. This protein stimulated GTP hydrolysis by purified Gly12 p21 more than 200-fold in vitro, but had no effect on Asp12 or Val12 mutants. A similar factor could be detected in extracts from mammalian cells. It thus appears that, in Xenopus oocytes, this protein maintains normal p21 in a biologically inactive, GDP-bound state through its effect on GTPase activity. Furthermore, it appears that the major effect of position 12 mutations is to prevent this protein from stimulating p21 GTPase activity, thereby allowing these mutants to remain in the active GTP-bound state.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Trahey, M -- McCormick, F -- New York, N.Y. -- Science. 1987 Oct 23;238(4826):542-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Biology, Cetus Corporation, Emeryville, CA 94608.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2821624" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Biological Assay ; Cytoplasm/*analysis ; Female ; GTP Phosphohydrolases/*metabolism ; Guanine Nucleotides/*physiology ; Guanosine Diphosphate/metabolism ; Guanosine Triphosphate/metabolism ; Guanylyl Imidodiphosphate/metabolism ; Hydrolysis ; Immunosorbent Techniques ; Mutation ; Oocytes/drug effects/growth & development ; Phosphoric Monoester Hydrolases/*metabolism ; Proteins/*pharmacology ; Proto-Oncogene Proteins/metabolism/pharmacology/*physiology ; Proto-Oncogene Proteins p21(ras) ; Structure-Activity Relationship ; Xenopus laevis
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  • 36
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1987-01-16
    Description: The search for genetic damage in neoplastic cells now occupies a central place in cancer research. Diverse examples of such damage are in hand, and they in turn hint at biochemical explanations for neoplastic growth. The way may be open to solve the riddles of how normal cells govern their replication and why cancer cells do not.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bishop, J M -- CA12705/CA/NCI NIH HHS/ -- SO7 RR05355/RR/NCRR NIH HHS/ -- New York, N.Y. -- Science. 1987 Jan 16;235(4786):305-11.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/3541204" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Division ; Chromosome Deletion ; DNA Damage ; DNA, Neoplasm/genetics ; Gene Amplification ; Humans ; Mutation ; Neoplasms/*genetics/pathology ; *Oncogenes ; *Proto-Oncogenes ; Retroviridae/genetics ; Translocation, Genetic
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  • 37
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1987-07-24
    Description: A novel approach to engineering enzyme specificity is presented in which a catalytic group from an enzyme is first removed by site-directed mutagenesis causing inactivation. Activity is then partially restored by substrates containing the missing catalytic functional group. Replacement of the catalytic His with Ala in the Bacillus amyloliquefaciens subtilisin gene (the mutant is designated His64Ala) by site-directed mutagenesis reduces the catalytic efficiency (kcat/Km) by a factor of a million when assayed with N-succinyl-L-Phe-L-Ala-L-Ala-L-Phe-p-nitroanilide (sFAAF-pNA). Model building studies showed that a His side chain at the P2 position of a substrate bound at the active site of subtilisin could be virtually superimposed on the catalytic His side chain of this serine protease. Accordingly, the His64Ala mutant hydrolyzes a His P2 substrate (sFAHF-pNA) up to 400 times faster than a homologous Ala P2 or Gln P2 substrate (sFAAF-pNA or sFAQF-pNA) at pH 8.0. In contrast, the wild-type enzyme hydrolyzes these three substrates with similar catalytic efficiencies. Additional data from substrate-dependent pH profiles and hydrolysis of large polypeptides indicate that the His64Ala mutant enzyme can recover partially the function of the lost catalytic histidine from a His P2 side chain on the substrate. Such "substrate-assisted catalysis" provides a new basis for engineering enzymes with very narrow and potentially useful substrate specificities. These studies also suggest a possible functional intermediate in the evolution of the catalytic triad of serine proteases.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Carter, P -- Wells, J A -- New York, N.Y. -- Science. 1987 Jul 24;237(4813):394-9.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/3299704" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Enzymes/*metabolism ; Models, Molecular ; Molecular Conformation ; Mutation ; Protein Binding ; Protein Conformation ; Substrate Specificity ; Subtilisins/genetics/*metabolism
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  • 38
    Publication Date: 1987-06-05
    Description: The v-sis oncogene encodes a platelet-derived growth factor (PDGF)-related product whose transforming activity is mediated by its functional interaction with the PDGF receptor. PDGF, as well as processed forms of the v-sis gene product, is a disulfide-linked dimer with eight conserved cysteine residues in the minimum region necessary for biologic activity. Site-directed mutagenesis of the v-sis gene revealed that each conserved cysteine residue was required directly or indirectly for disulfide-linked dimer formation. However, substitution of serine for cysteine codons at any of four positions had no detrimental effect on transforming activity of the encoded v-sis protein. These results establish that interchain disulfide bonds are not essential in order for this protein to act as a functional ligand for the PDGF receptor. The remaining four substitutions of serine for cysteine each inactivated transforming function of the molecule. In each case this was associated with loss of a conformation shown to involve intramolecular disulfide bonds. These studies provide insight into the role of individual cysteine residues in determining the structure of the sis/PDGF molecule critical for biological activity.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Giese, N A -- Robbins, K C -- Aaronson, S A -- New York, N.Y. -- Science. 1987 Jun 5;236(4806):1315-8.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/3035718" target="_blank"〉PubMed〈/a〉
    Keywords: Antigens, Polyomavirus Transforming ; Antigens, Viral, Tumor/analysis/*physiology ; Cell Transformation, Viral ; Cross Reactions ; Cysteine ; *Genes, Viral ; Mutation ; Oncogene Proteins, Viral/analysis/*physiology ; *Oncogenes ; Platelet-Derived Growth Factor/analysis/physiology ; Protein Conformation ; Protein Processing, Post-Translational ; Receptors, Cell Surface/metabolism ; Receptors, Platelet-Derived Growth Factor ; Retroviridae/*genetics ; Sarcoma Virus, Woolly Monkey/*genetics ; Serine ; Transfection
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  • 39
    Publication Date: 1987-08-28
    Description: The alpha 2 protein, the product of the MAT alpha 2 gene, is a regulator of cell type in the yeast Saccharomyces cerevisiae. It represses transcription of a group of cell type-specific genes by binding to an operator located upstream of each target gene. Fifteen in-frame deletions within the coding region of the MAT alpha 2 gene were constructed. The deletion alleles were examined for phenotypes conferred in vivo, and the encoded mutant proteins were assayed for ability to bind specifically to the operator in vitro. This analysis has revealed that the sequence-specific DNA-binding domain of alpha 2 is located within a region of 68 amino acids. This region of alpha 2 has significant homology with the homeo domain, a conserved sequence found in the products of several Drosophila homeotic and segmentation genes. In addition, there is a class of mutant alpha 2 proteins that binds tightly and specifically to the operator in vitro, but fails to repress transcription in vivo.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hall, M N -- Johnson, A D -- GM35284/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1987 Aug 28;237(4818):1007-12.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2887035" target="_blank"〉PubMed〈/a〉
    Keywords: Base Sequence ; DNA, Fungal/genetics ; DNA-Binding Proteins/*genetics ; Drosophila melanogaster/genetics ; Genes, Homeobox ; *Genes, Regulator ; Mutation ; Phenotype ; Repressor Proteins/*genetics ; Saccharomyces cerevisiae/*genetics ; Transcription Factors/*genetics
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  • 40
    Publication Date: 1987-06-19
    Description: Individual protein-binding sites within the mouse immunoglobulin heavy chain and kappa light chain gene enhancers were altered, making it possible to examine the functional role of the sites during transcription. The E motifs, which bind factors that are present in many if not all cells, mostly behave as transcriptional activating sites. The only known heavy chain enhancer site that binds a lymphocyte-specific factor, the "octamer" site, plays a critical role in transcription but only in a truncated form of the enhancer. In the full enhancer, no one site is crucial because of an apparent functional redundancy. The site in the kappa enhancer that binds a factor specific to mature B cells, kappa B, was crucial to the constitutive activity of the enhancer in B cells. This factor is also inducible in pre-B cells, and the site was necessary for inducibility of the kappa enhancer. Thus, the sites defined by protein binding are important for the functional activity of immunoglobulin enhancers, with the sites that bind proteins restricted in their cellular distribution playing the most important roles.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lenardo, M -- Pierce, J W -- Baltimore, D -- New York, N.Y. -- Science. 1987 Jun 19;236(4808):1573-7.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/3109035" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Binding Sites ; *Enhancer Elements, Genetic ; *Genes, Regulator ; Immunoglobulin Heavy Chains/*genetics ; Immunoglobulin kappa-Chains/*genetics ; Lymphocytes/immunology ; Mice ; Mice, Inbred BALB C ; Multiple Myeloma/metabolism ; Mutation ; *Transcription, Genetic
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  • 41
    Publication Date: 1987-03-13
    Description: It is a generally accepted principle of biology that a protein's primary sequence is the main determinant of its tertiary structure. However, the mechanism by which a protein proceeds from an unfolded, disordered state to a folded, relatively well-ordered, native conformation is obscure. Studies have been initiated to examine the "genetics" of protein folding, with mutants of bovine pancreatic trypsin inhibitor (BPTI) being used to explore the nature of the specific intramolecular interactions that direct this process. Previous work with BPTI chemically modified at cysteines 14 and 38 indicated that transient disulfide bond formation by these residues contributed to efficient folding at 25 degrees C. In the present work, mutants of BPTI in which these cysteines were replaced by alanines or threonines were made and the mutant proteins were produced by a heterologous Escherichia coli expression system. At 25 degrees C in vitro, the refolding behavior of these mutants was characterized by a pronounced lag. However, when expressed at 37 degrees C in E. coli, or when refolded at 37 degrees or 52 degrees C in vitro, the mutant proteins folded readily into the native conformation, albeit at a rate somewhat slower than that exhibited by wild-type BPTI. These results indicate that, at physiological temperatures, BPTI lacking cysteines 14 and 38 can refold quantitatively.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Marks, C B -- Naderi, H -- Kosen, P A -- Kuntz, I D -- Anderson, S -- New York, N.Y. -- Science. 1987 Mar 13;235(4794):1370-3.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2435002" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; *Aprotinin/genetics ; *Cysteine ; Disulfides ; Escherichia coli/genetics ; Mutation ; Protein Conformation ; Temperature
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  • 42
    Publication Date: 1987-06-05
    Description: The molecular analysis of genes identified by mutations is a major problem in mammalian genetics. As a step toward this goal, preparative field inversion gel electrophoresis (FIGE) was used to selectively isolate clones from the environment of genetically linked markers, and to select a subset of these clones containing sequences next to specific restriction sites rare in mammalian DNA. This approach has been used to generate a library highly enriched in sequences closely linked to the cystic fibrosis marker met. One clone derived from the end of a Not I restriction fragment containing the met sequence was analyzed in detail and localized within a long range map to a position 300 kilobase pairs 5' of the metD sequence.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Michiels, F -- Burmeister, M -- Lehrach, H -- New York, N.Y. -- Science. 1987 Jun 5;236(4806):1305-8.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/3035716" target="_blank"〉PubMed〈/a〉
    Keywords: Bacteriophage lambda ; *Chromosome Mapping ; Cloning, Molecular ; Cystic Fibrosis/*genetics ; DNA Restriction Enzymes ; Electrophoresis/*methods ; *Genetic Markers ; Genetic Vectors ; Humans ; Mutation ; Nucleic Acid Hybridization ; Repetitive Sequences, Nucleic Acid
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  • 43
    Publication Date: 1987-09-04
    Description: Many spontaneous mutations are caused by the insertion or excision of DNA elements. Since most mutations are deleterious, evolution should favor a mechanism for genetically controlling the rate of movement of transposable elements in most, if not all, organisms. In Drosophila melanogaster a syndrome of correlated genetic changes, including mutation, chromosome breakage, and sterility, is observed in the hybrid progeny of crosses between different strains. This syndrome, which is termed hybrid dysgenesis, results from the movement of P-DNA elements. What is not clear is whether the movement of other types of transposable elements is under the same coordinated control. In this study the ability of hybrid dysgenesis to increase the rate of excision of 12 DNA elements at 16 mutant alleles and to induce insertion-bearing mutations to change to other mutant states was tested. The data show that hybrid dysgenesis caused by P-element transpositions does not act as a general stimulus for the movement of other Drosophila transposable elements.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Woodruff, R C -- Blount, J L -- Thompson, J N Jr -- K04-ES-00087/ES/NIEHS NIH HHS/ -- New York, N.Y. -- Science. 1987 Sep 4;237(4819):1206-18.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2820057" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Crosses, Genetic ; *DNA Transposable Elements ; Drosophila melanogaster/*genetics ; Female ; Gonadal Dysgenesis ; Hybridization, Genetic ; Male ; Mutation ; Probability
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