MutY is a DNA glycosylase responsible for excising adenine base-paired opposite 8-oxo-7,8-dihydroguanine (OG), which is formed by the oxidation of guanine. If left unrepaired OG:A mispairs result in the formation of a T:A base pair from the original G:C base pair causing a point mutation in the DNA. This mispair is rare and non-helix distorting and therefore presents a significant challenge to recognition and repair by the enzyme as it searches the genome for damage. By using nucleobase analogs of OG and A, we seek to understand the structural features OG:A that facilitate recognition by the enzyme and the subsequence excision of adenine. We evaluated the effect of the different base modifications on binding affinities, rate of catalysis and extent of overall repair in a cellular context. Such studies may be used towards developing a structure activity relationship (SAR) that can help us understand the structural basis for lesion identification and excision by MutY.

Nucleobase analogs as probes for substrate recognition and repair by DNA glycosylase MutY

253rd National Meeting (2017)

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