Document Type



Master of Science (MS)



First Advisor's Name

Yuk-Ching Tse-Dinh

First Advisor's Committee Title

Committee chair

Second Advisor's Name

Yuan Liu

Second Advisor's Committee Title

Committee member

Third Advisor's Name

Jaroslava Miksovska

Third Advisor's Committee Title

Committee member


Topoisomerase Inhibitors, Supercoiling, Flavonoids, Anthocyanidins, DNA Relaxation

Date of Defense



Inhibition of human topoisomerase I have been shown to reduce excessive transcription of PAMP-induced genes based on prior studies, which offers a solution to offset complications of sepsis such as tissue damage and organ failure. The enzyme resolves the topological constraints on DNA that encodes these genes. The aim of this study is to identify human topoisomerase I (HTop1) inhibitors that can a.) prevent the relaxation of negative supercoiled plasmid DNA by HTop1 and b.) reduce HTop1 binding to DNA and formation of covalent cleavage complex (HTop1cc) utilizing a novel yeast screening system. Top hits from in-silico screening conducted by our collaborator showed moderate to no inhibition. The natural products anthocyanidins, delphinidin, and cyanidin chloride were shown to restore the growth of yeast expressing a lethal HTOP1 mutant by preventing HTop1cc. Myricetin inhibited yeast growth in the presence and absence of HTop1 overexpression, which requires further investigation. This novel yeast screening approach can offer potential insights into the inhibitor’s mechanism of action.



Included in

Biochemistry Commons



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