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Molecular basis of transcriptional mutagenesis at 8-oxoguanine.

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.

SUBMITTER: Damsma GE

PROVIDER: S-EPMC2797236 | biostudies-literature | 2009 Nov

REPOSITORIES: biostudies-literature

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Molecular basis of transcriptional mutagenesis at 8-oxoguanine.

Damsma Gerke E GE Cramer Patrick P

The Journal of biological chemistry 20090916 46

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 ...[more]

PMID: 19758983

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