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Development Of Selective Inhibitors Of Dna Polymerase Delta: A Thesis, Robert Vincent Talanian Aug 1989

Development Of Selective Inhibitors Of Dna Polymerase Delta: A Thesis, Robert Vincent Talanian

GSBS Dissertations and Theses

This thesis is divided into three parts, united by the theme of the development of selective inhibitors of mammalian cell DNA polymerase delta (pol δ). The first part consists of an investigation of the cytotoxic mechanism(s) of certain 2-substituted adenine analogs, selected on the basis of their inhibitory properties towards DNA polymerase alpha (pol α) and mammalian cell DNA synthesis. The second is a direct search for inhibitors of isolated pol δ, and an investigation of inhibitory mechanisms. The third consists of measurement of the effects of a selective pol δ inhibitor on cellular DNA synthesis.

Mechanism of Cytotoxicity ...


Proteolytic Cleavages Of Molecules Involved In Antigen Processing And Presentation: A Thesis, Lawrence James Thomas Aug 1989

Proteolytic Cleavages Of Molecules Involved In Antigen Processing And Presentation: A Thesis, Lawrence James Thomas

GSBS Dissertations and Theses

The overall goal of my thesis research was to understand better the mechanisms that control antigen processing and presentation by class II MHC molecules. Towards this goal I investigated ways in which the physical structure and post-translational modifications of the class II MHC alpha and beta chains and associated molecules might serve to regulate antigen processing and presentation. Specifically, I investigated (1) a hypothesis that Ii might aid binding of foreign antigenic peptides to the class II MHC foreign antigen binding site (desetope), and the application of this hypothesis to the prediction of class II-presented peptides; (2) the proteolytic ...


Plasma Membrane Processes In Smooth Muscle: Characterization Of Ca2+ Transport And Muscarinic Cholinergic Receptors: A Thesis, Pamela A. Lucchesi Apr 1989

Plasma Membrane Processes In Smooth Muscle: Characterization Of Ca2+ Transport And Muscarinic Cholinergic Receptors: A Thesis, Pamela A. Lucchesi

GSBS Dissertations and Theses

The thesis research was designed to study the characteristics of two important physiological processes in smooth muscle: Ca2+ transport mediated by the plasmalemmal Ca2+-ATPase and muscarinic receptor-G protein interactions. In resting smooth muscle, several Ca2+ extrusion or sequestration processes offset the passive inward leak of Ca2+. Although biochemical evidence suggests that the plasmalemmal Ca2+ pump plays a key role in this process, the precise role of this enzyme could not be proven until a reliable estimate of the inward Ca2+ leak was measured. Recent studies using dispersed smooth muscle cells from the toad ...


Structural Determinants Of Mrna Turnover In Yeast: A Thesis, David Herrick Jan 1989

Structural Determinants Of Mrna Turnover In Yeast: A Thesis, David Herrick

GSBS Dissertations and Theses

Large differences exist in the decay rates of individual mRNAs yet the molecular basis for such differences is substantially unknown. We have developed a procedure for the measurement of individual mRNAs in the yeast Saccharomyces cerevisiae which utilizes northern or dot blotting to quantitate the levels of individual mRNAs after thermal inactivation of RNA polymerase II in an rpb1-1 temperature-sensitive mutant strain (RY260). To assess the reliability of half-life measurements obtained in this manner, we have compared the results of this procedure to results obtained by three other procedures (pulse-chase analysis, approach to steady-state labeling, and inhibition of transcription with ...