Student Research - Biochemistry and Molecular Biology
Sarah Nicolson
Insight into substrate recognition by FPG and hOGG, two DNA repair enzymes
Abstract: The damaged DNA base 8-oxo-2'-deoxyguanosine (OdG), which is produced by reactive oxygen species, is highly mutagenic and has been linked to diseases such as rheumatoid arthritis, lupus, and cancer. We worked with two repair glycosylases, FPG and hOGG (the bacterial and human homologues, respectively), that recognize and remove this base from DNA. Since OdG differs from dG (which is not recognized by either FPG or hOGG) at only two positions, C8 and N7, it was believed that one or both of these sites is used for substrate recognition by the enzymes. We evaluated three analogs of OdG to study these sites: SdG (8-thio-2'-deoxyguanosine), which differs from OdG at only the C8 position, MdG (7-methyl-8-oxo-guanosine), which differs from OdG at only the N7 position, and AdG (7-deaza-2'-deoxyguanosine), which differs from OdG at both the N7 and C8 positions. It was found that all three analogues were active with both FPG and hOGG, suggesting that OdG recognition is signaled by the absence of an sp2 hybridized N7.
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