Professor Don Dennis

RESEARCH

The area of information transfer has been of interest and focus for the past decade in our laboratory. We have developed a model for the mechanics of the transcription polymerization process which involves a rotational translocation. This hypothesis depicts the polymerase enzyme as a spinning element containing two active sites which are used in an alternating sequence such that each 180° of rotation adds another nucleotide monomer to the growing chain.

Our current test system is the HIV- reverse transcriptase enzyme conducting second strand synthesis. The characterization of the active site(s) for each of several successive registries is being determined using the photoaffinity probe 4-Thio dUTP as well as several other probes.

The results of recent experiments are reported where a specific hexapeptide of the p66 subunit is located at the binding domain of the active site of the HIV-1 reverse transcriptase enzyme.

 

(Original hypothesis)

Dennis, D.; Sylvester, J. E. (1981) FEBS LETT. 124 135.

(Current result)

Lin, S.; Henzel, W. J.; Nayak, S.; Dennis, D. (1998) JBC

 Publications

  1. Studies on the Toxicity and Antileukemic Action of 6-Mercaptopurine in Mice; Goldin, A., Venditti, J. M., Humphreys, S. R., Dennis, D., Mantel, N., and Greenhouse, S. W.; An. New York Aca. Sc., 60, 251-266 (1954).
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  3. Factors Influencing the Specificity of Action of an Antileukemic Agent (Aminopterin). Multiple Treatment Schedules plus Delayed Administration of Critrovorum Factor; Goldin, A., Venditti, J. M., Humphreys, S. R., Dennis, D., Mantel, N., and Greenhouse, S. W.; Cancer Res., 15, 57-61 (1955).
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  5. Potentiation of Pentobarbital Anesthesis by Isonicotinic Acid Hydrazide and Related Compounds; Goldin, A., Dennis, D., Venditti, J. M., and Humphreys, S. R.; Science, 212, 364-365 (1955).
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  7. A Quantitative Comparison of the Antileukemic Effectiveness of Two Folic Acid Antagonists in Mice; Goldin, A., Venditt, J. M., Humphreys, S. R., Dennis, D., Mantel, N., and Greenhouse, S. W.; J. Nat'l Cancer Inst., 15, 1657 (1955).
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  9. Studies on the Management of Mouse Leukemia (L1210) with Antagonists of Folic Acid; Goldin, A., Venditti, J. M., Humphreys, S. R., Dennis, D., and Mantel, N.; Cancer Res. 15, 742-47 (1955).
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  11. An Investigation into the Synergistic Antileukemic Action of Amethopterin and 6-Mercaptopurine in Mice; Goldin, A., Venditti, J. M., Humphreys, S. R., Dennis, D., Mantel, N., and Greenhouse, S. W.; J. Nat'l Cancer Inst., 16, 129 (1955).
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  13. Factors Influencing the Specificity of Action of an Antileukemic Agent (Aminopterin): Host Age and Weight; Goldin, A., Venditti, J. M., Humphreys, S. R., Dennis, D., and Mantel, N.; J. Nat'l Cancer Inst., 16, 709 (1955).
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  15. Growth Studies on Sarcoma 37 in Mice; Goldin, A., Humphreys, S. R., Venditti, J. A., Dennis, D., and Mantel, N.; J. Nat'l. Cancer Inst., 16, 1207 (1956).
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  17. D. and L. Lactic Acid Dehydrogenases in Lactobacillus Plantarum; Dennis, D., Kaplan, N. O., J. Biol. Chem., 235, 810 (1960).
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  19. Thesis, Ph.D., 1959, "Lactic Acid Racemization", Brandeis University.
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  21. Lactic Acid Racemization in Clostridium Butylicum; Dennis, D., Kaplan, N. O., Biochem. Zeits., 338, 485-495 (1963).
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  23. Lactic Acid Racemization in "Methods in Enzymology", Vol. V, Kaplan, N. O. and Colowick, S., Ed., New York, Academic Press, 1961.
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  25. Lactic Acid Racemization; Dennis, D., Reichlin, M., and Kaplan, N. O., Anls. N. Y. Aca. Sci., 119, 868-876 (1965).
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  27. Lactic Acid Racemization in Clostridium Butylicum. Evidence for a Direct Internal Hydride Shift, Shapiro, S. S., Dennis, D., Biochem., 4, 2283 (1965).
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  29. Lactic Acid Racemization in Cl. Butylicum: 18O Exchange Studies; Shapiro, S. S. and Dennis, D., BBRC, 22, 635 (1966).
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  31. The Use of Specific Macromolecular Complexing Agents for Enzyme Purification: Beef Heart Lactic Dehydrogenase; Anal. Biochem., 24, 541 (1968).
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  33. Substrate Concentration Dependence of Deuterium Isotope Effects on Beef Heart Lactate Dehydrogenase; Cantwell, A. and Dennis, D.; BBRC, 41, 1166 (1970).
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  35. The Synthesis & Single Crystal X-ray Structure Determination of 9 a Cyano-19-Nor-testosterone; Dennis, D., Stanford, R.; Synthetic Comm., 2 (3), 175 (1972).
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  37. Messenger RNA Structure: Compatibility of Hairpin Loops with Protein Sequence; White, H. B., Laux, B., Dennis, D.; Science, 175, 1264 (1972).
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  39. Asymmetric Phospholipid Bilayer Membranes: Formation and Electrical Characterization; Michaels, D. and Dennis, D.; BBRC, 51, 357 (1973).
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  41. Human a Chain Globin Messenger: Prediction of a Nucleotide Sequence, Laux, B., Dennis, D., White, H. B., BBRC, 54 #3, 894 (1973).
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  43. Crystal and Molecular Structure of Firefly D(-) Luciferin; Dennis, D., Stanford, R.; Acta Cryst., B29, 1053 (1973).
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  45. Lactate Racemace: Direct Evidence for an a Carbonyl Intermediate; Cantwell, A., Dennis, D.; Biochemistry, 13, 287 (1974).
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  47. Crystal and Molecular Structure of Bis Diethyl Bis [1-pyrazolyl]Borato Nickel(II), Echols, H. M., Dennis, D., Acta Cryst., B30, 2173 (1974).
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  49. The Crystal and Molecular Structure of a Heteronium Bromide, Coughenour, K. N., Dennis, D., Acta Cryst., B31, 1229 (1975).
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  51. Lactate Racemase: Hydroxylamine-Dependent 18O Exchange of the a-Hydroxyl of Lactic Acid, Pepple, J. S., Dennis, D., Biochimica et Biophysica Acta, 429, 1036 (1976).
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  53. The Crystal and Molecular Structure of Bis[dihydrobis-(1-pyrazolyl)-borato]nickel(II): Evidence for the Absence of Ni-H Interaction in Polypyrazoly Borates of Nickel, Echols, H. M., Dennis, D., Acta Cryst., B32, 1627 (1976).
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  55. RNA Polymerase: Potent Competitive Inhibition by D-Ribose-5-Triphosphate and Other Pentose Polyphosphates, Sylvester, J. E., Dennis, D., BBRC 75 #3, 667 (1977).
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  57. RNA Polymerase: Potent Linear Competitive Inhibition by Arabinose-5-Triphosphate Compared to Non-Inhibition by 5' Ara-ATP, Dennis, D., Jurgensen, S., Sylvester, J., BBRC 94 #1, 205 (1980).
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  59. RNA Polymerase: A Model for Rotational Translocation, Dennis, D., Sylvester, J., F.E.B.S. Letters 124 #2, 135 (1981).
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  61. RNA Polymerase: Linear Competitive Inhibition by Bis-(3'®5')-cyclic dinucleotides, -NPNP-, Hsu, C-Y. J., Dennis, D.; Nucleic Acids/research 10 #18, 5637-5647 (1982).
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  63. RNA Polymerase: Correlation Between Transcript Length, Abortive Product Synthesis, and Formation of a Stable Ternary Complex, Kinsella, L., Hsu, C-Y. J., Schultz, W. and Dennis, D., Biochemistry 21, 2719-2723 (1982).
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  65. RNA Polymerase: Synthesis and Kinetic Inhibition by 9-(3'-Azido-3'-Deoxy-b-D-Xylofuranosyl) Derivatives, Panka, D. and Dennis, D.; J. Biol. Chem. 259 #13, 8384-8387.
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  67. RNA Polymerase: Direct Evidence for Two Active Sites Involved in Transcription, Dennis, D.; Nucleic Acids Research 16 261-263 13th Symposium on Nucleic Acids Chemistry (Osaka, Japan) 1985.
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  69. Synthesis and Physical Characterization of Bis 3'®5' Cyclic Dinucleotides (-NpNp-): RNA Polymerase Inhibitors, Hsu, C-Y., J. and Dennis, D.; with Jones, R. A.; Nucleosides and Nucleotides 4 (3) 377-389 (1985).
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  71. RNA Polymerase: Direct Evidence for Two Active Sites Involved in Transcription, Panka, D., and Dennis, D.; J. Biol. Chem. 260 #3 1427-1431 (1985).
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  73. RNA Polymerase: Direct Evidence for a Unique Topographical Site for Initiation, Ruetsch, N., and Dennis, D.; J. Biol. Chem. 260 #30 16310-16315 (1985).
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  75. RNA Polymerase: Limit Cognate Primer for Initiation and Stable Ternary Complex Formation, Ruetsch, N., and Dennis, D.; J. Biol. Chem. 262 #4 1674-1679 (1987).
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  77. Formation and Characterization of Precise Eucaryotic Transcription Complexes Using a Semisynthetic DNA Template and Specific Oligoribonucleotide Primers, Mougey, E., and Dennis, D.; Anal. Biochem. 171 256-65 (1988).
  78. Yeast RNA Polymerase I: Derivatization of the 190 and 135 Subunits by 4-Thiouridine Monophosphate Positioned Uniquely at the 3' Terminus of an Enzyme-Bound 32P-Containing Transcript Initiated by a Triribonucleotide Primer on Synthetic Single-Stranded DNA, Kelly, S., Sheng, N., and Dennis, D.; J. Biol. Chem. 265 #14 7787-7792 (1990).
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  80. Wheat Germ and Yeast RNA Polymerase II: Photoaffinity Labeling by 4-Thiouracil 5'-Monophosphate Positioned Uniquely at the 3' End of an Enzyme-Bound [32P]-Containing Transcript, Sheng, N., Mougey, E. B., Kelly, S., and Dennis, D.; Biochemistry 32 2248-2253 (1993).
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  82. Active Site Labeling of HIV-1 Reverse Transcriptase, Sheng, N., and Dennis, D.; Biochemistry 32 4938-4942 (1993).
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  84. Photoaffinity Labeling by S4ddUTP of the HIV-1 Reverse Transcriptase Active Site During Synthesis: Sequence of the Unique Labeled Hexapeptide, Lin, S., Henzel, W. J., Nayak, S., and Dennis, D.; JBC (1998) in press.