Activation of Ras signaling pathway by 8-oxoguanine DNA glycosylase bound to its excision product, 8-oxoguanine

Istvan Boldogh, Gyorgy Hajas, Leopoldo Aguilera-Aguirre, Muralidhar L. Hegde, Zsolt Radak, Attila Bacsi, Sanjiv Sur, Tapas K. Hazra, Sankar Mitra

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8-Oxo-7,8-dihydroguanine (8-oxoG), arguably the most abundant base lesion induced in mammalian genomes by reactive oxygen species, is repaired via the base excision repair pathway that is initiated with the excision of 8-oxoG by OGG1. Here we show that OGG1 binds the 8-oxoG base with high affinity and that the complex then interacts with canonical Ras family GTPases to catalyze replacement of GDP with GTP, thus serving as a guanine nuclear exchange factor. OGG1-mediated activation of Ras leads to phosphorylation of the mitogen-activated kinases MEK1,2/ERK1,2 and increasing downstream gene expression. These studies document for the first time that in addition to its role in repairing oxidized purines, OGG1 has an independent guanine nuclear exchange factor activity when bound to 8-oxoG.

Original languageEnglish (US)
Pages (from-to)20769-20773
Number of pages5
JournalJournal of Biological Chemistry
Issue number25
StatePublished - Jun 15 2012


ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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