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Reference: Damsma GE and Cramer P (2009) Molecular basis of transcriptional mutagenesis at 8-oxoguanine. J Biol Chem 284(46):31658-63

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Abstract

Structure-function analysis reveals the mechanism of yeast RNA polymerase (Pol) II transcription over 8-oxoguanine (8oxoG), the major DNA lesion resulting from oxidative stress. When Pol II encounters 8oxoG in the DNA template strand, it can misincorporate adenine, which forms a Hoogsteen base pair with 8oxoG at the active center. This requires rotation of the 8oxoG base from the standard anti to an uncommon syn conformation, which likely occurs during 8oxoG loading into the active site. The misincorporated adenine escapes intrinsic proofreading, resulting in transcriptional mutagenesis that is observed directly by mass spectrometric RNA analysis.

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Journal Article
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Damsma GE, Cramer P
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