Student Research - Biochemistry and Molecular Biology

Matt Summers

Studies on the effect of C8 steric bulk on the promutagenicity of 8-oxo-2'-deoxyguanosine

Abstract: When subjected to reactive oxygen species, the DNA base 2'deoxyguanosine (dG) can become oxidized to 8-oxo-2'deoxyguanosine (OdG). This damaged form acts as a DNA promutagen and has been linked to several diseases including lupus, rheumatoid arthritis, and cancer. These mutations occur as a result of the ability of OdG to form stable base pairs with both 2'deoxycytidine (dC) and 2'deoxyadenosine (dA). If DNA polymerases incorporate dC opposite of OdG then no mutation occurs, however if DNA polymerases incorporate dA opposite of OdG then a subsequent round of replication will result in a dG to dT transversion. We are attempting to highlight the important structural differences between OdG and dG and determine which structural change is important to DNA polymerase selectivity. OdG differs from dG at only two positions, C8 and N7, and therefore we used two analogs of OdG to study the effects at these two positions. The two analogs studied were SdG (8-thio-2'-deoxyguanosine), which mimics the steric bulk seen by OdG at C8, and CldG (8-chloro-2'-deoxyguanosine) which mimics the steric bulk at C8, but also does not have hydrogen bond donating capability at N7. By studying these analogs and the preferences of various polymerases to insert dC or dA opposite them, information can be obtained about the causes of OdG mutation.

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Presentor	Matt Summers
Mentor	Dr. Michelle Hamm