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 has revealed the mechanism of yeast RNA polymerase II transcription at 8-oxoguanine (8-oxoG), the major DNA lesion resulting from oxidative stress. When polymerase II encounters 8-oxoG in the DNA template strand, it can misincorporate adenine, which forms a Hoogsteen bp with 8-oxoG at the active center. This requires rotation of the 8-oxoG base from the standard anti- to an uncommon syn-conformation, which likely occurs during 8-oxoG 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 | Research Support, Non-U.S. Gov't
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Damsma GE, Cramer P
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