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.