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protein. However, helicase assays showed that the mutant unwound DNA more efficiently. This means that the inserted element inhibits the helicase activity of PriA.
Investigation of a 70 Amino Acid Insert in the DNA Binding Domain of Deinococcus Radiodurans PriA
STUDENTS Erin E Gallagher ADVISORS Matthew E Lopper LOCATION, TIME RecPlex, 11:00 AM-12:30 PM Chemistry, Poster - Honors Thesis The goal of this research is to study the replication restart pathway of an unusually radiation resistant species of bacteria, D. radiodurans. This pathway is used to restart DNA replication after DNA damage has been repaired. Specifically, I investigated the function of an additional 70 amino acid element in the DNA binding domain of D. radiodurans PriA. It was hypothesized that there will be a relation between the insert and the radiation resistance seen in D. radiodurans. This will be accomplished by cloning the DNA binding domain of D. radiodurans priA. The recombinant PriA protein will be analyzed with DNA binding assays. Attempts will also be made to crystallize the DNA binding domain of D. radiodurans PriA to obtain a high resolution structural model. It is predicted that the additional sequence in PriA will affect the protein’s ability to bind to DNA, and that this difference in binding will partly explain the increased radiation resistance seen in D. radiodurans.
Mechanistic studies of inhibitors of DNA replication restart pathways in Neisseria gonorrhea
STUDENTS DRK Chaitanya Aduri ADVISORS Matthew E Lopper LOCATION, TIME RecPlex, 11:00 AM-12:30 PM Chemistry, Poster - Graduate Research Complete and faithful replication of a cell’s genetic information is an essential process. Many enzymes are involved in the successful duplication of genetic information and the integrity of these enzymes can be compromised when they encounter DNA damage. Bacterial cells use a pathway called DNA replication restart to resume DNA replication following a disruptive encounter of the DNA replication enzymes with DNA damage. This pathway is catalyzed by primosome proteins, including PriA, PriB, PriC, DnaT, DnaB, DnaC, and DnaG. The importance of DNA replication restart for bacterial cell survival is demonstrated by the inability of strains that carry mutations in key primosome genes to grow and resist DNA damaging agents. Furthermore, this pathway is specific for bacterial cells: human cells don’t use the same replication restart pathway and they don’t encode genes for the primosome proteins that function in bacteria. Since DNA replication restart pathways are essential for bacterial cell growth and survival and are notably absent in human cells, we seek to answer the following question: can bacterial DNA replication restart pathways be targeted with novel antibacterial compounds? In order to answer this question, we have developed an enzyme based assay for high-throughput inhibitor screening to identify compounds that block the function of the primosome proteins PriA and PriB. Several interesting lead compounds have already been identified from the preliminary screening. In this study, the lead compounds have been validated as legitimate inhibitors and characterized with respect to their potency and mechanism of action.
Preparation of some new epoxy-functionalized phosphonate and phosphate esters as reactive flame retardants for polyurethane
STUDENTS Karl J Seiwert ADVISORS Vladimir A Benin LOCATION, TIME RecPlex, 11:00 AM-12:30 PM Chemistry, Poster - Capstone Project New phosphonate and phosphate esters, containing an epoxide functionality, have been prepared and characterized, in an effort to design and implement the next generation of reactive monomers for polymers with inherent flame-retardant properties. Several synthetic pathways were explored and utilized. Thus, phosphonate esters were successfully prepared using protocols based on the Michaelis-Arbuzov reaction or alkylation of dialkyl phosphites, with or without subsequent epoxidation. Phosphate esters were generated from chlorophosphates, followed by epoxidation. 51