Gene Regulation Through Artificially Induced DNA Conformational Changes

The conformation of DNA has been shown to play an important role in the regulation of gene expression. A consequence of this finding is that agents that alter the conformation of DNA should also affect the regulation of gene expression. To explore this, we used tethered-triple helix oligonucleotides (TFO) to bend DNA. We show that the expression of a luciferase gene is regulated by the presence of an induced DNA bend. Bends occurring in the same orientation as RNA polymerase binding result in a 93% increase in expression. In contrast, bends induced in that opposite direction resulted in a 51% decrease in expression. These results prompted us to investigate the synthesis of three small molecules with the potential to induce a sequence selective bend in DNA. These studies revealed that the compounds were able to induce a DNA bend counter to an intrinsic bend present in a target DNA fragment.

Name thesis:degree_name

MS

Level thesis:degree_level

Worldwide Access

Discipline thesis:degree_discipline

Medicinal Chemistry

Year dc:date.available

2008

Author dc:creator

• Bednarski, David

Contributors dc:contributor

• Steven Firestine
• Aleem Gangjee
• David A. Johnson
• Marc W. Harrold

• DNA bending
• TFO
• transcription regulation

Language dc:language

English

Repository record dc:identifier

https://dsc.duq.edu/etd/29

OAI identifier oai:identifier

oai:dsc.duq.edu:etd-1028