4.6 Article

Molecular Basis of Transcriptional Mutagenesis at 8-Oxoguanine

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JOURNAL OF BIOLOGICAL CHEMISTRY
卷 284, 期 46, 页码 31658-31663

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AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M109.022764

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  1. Deutsche Forschungsgemeinschaft
  2. Sonderforschungsbereich [SFB646]
  3. Transregio 5

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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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