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.