RUI: Chemical Investigations into the Bioactivity of the DNA Lesion 8-Oxo-2'-deoxyguanosine

University Of Richmond, Richmond VA

Investigators

Abstract

The oxidatively damaged 2'-deoxyguanosine (dG) derivative 8-oxo-2'-deoxyguanosine (OdG) is one of the most prominent DNA lesions and has been linked to ageing as well as several diseases including cancer. Unlike dG which base pairs only with 2'-deoxycytosine (dC) in DNA, OdG can pair with both dC and 2'-deoxyadenosine (dA), thus allowing for mutations during replication. Due to its prominence and promutagenic character, cells have evolved three different repair mechanisms that help lessen the impact of OdG on cells. With the support of this RUI Award from the Chemistry of Life Processes Program, Professor Michelle Hamm of the Department of Chemistry at the University of Richmond will continue her research to better understand the exact steric and/or electronic properties that dictate the bioactivity of OdG. Her lab synthesizes nucleotide analogues on the spectrum between dG and OdG, incorporates them into DNA, and uses them in biochemical experiments focused on the base pairing, replication, and repair of OdG. By comparing the activities of the synthesized analogues to dG and OdG, the exact atomic factors that influence the bioactivity of OdG, and why it differs so strongly from dG, can be isolated. Only by understanding the specific properties and interactions that dictate the activity of a compound can one fully understand its role within the cell. This research will involve undergraduate students at a primarily undergraduate institution and provide training in the synthetic and biochemical techniques used in the proposed studies. The researchers will also learn important skills including time management, critical thinking, experimental design, and verbal and written communication. These activities will prepare them for research in academic or industrial settings, sparking interest in further study at an advanced level.