Expanding on “Uracil-DNA glycosylase efficiency is modulated by substrate rigidity”

Misincorporation of uracil bases into DNA can lead to mutations after transcription. Uracil-DNA glycosylase (UDG) is an enzyme that removes uracil bases from DNA, leaving an apurinic/apyrimidinic site. Different efficiencies of uracil base removal by UDG have been observed at different sites in DNA. A previous study found that UDG has a higher specificity constant for DNA sequences that are more flexible, specifically that those with uracil in a context of thymine adjacent on the 5’ side and adenine adjacent on the 3’ side (TUA sequence) bound UDG better than those with an adenine adjacent on the 5’ side and thymine adjacent on the 3’ side (AUT sequence) context. The purpose of this study is to expand the previous one by determining whether the ratios observed between TUA and AUT specificity constants within DNA sequences that are otherwise the same are also observed across a third sequence context that was not included in the first study. The hypothesis that same ratio would be observed is somewhat supported as the new sequence has a specificity constant of 1.24±0.043 ✕ 107 M-1s-1. However, conclusions to be drawn from this are limited by the wide margin of error seen among trials of the same concentrations.