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 Hazra, Sankar Mitra

Research output: Contribution to journalArticle

73 Citations (Scopus)

Abstract

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
Volume287
Issue number25
DOIs
StatePublished - Jun 15 2012

Fingerprint

DNA Glycosylases
Chemical activation
Guanine
ras Proteins
Purines
Phosphorylation
GTP Phosphohydrolases
Guanosine Triphosphate
Mitogens
Gene expression
DNA Repair
Reactive Oxygen Species
Ion exchange
Repair
Phosphotransferases
Genes
Genome
Gene Expression
8-hydroxyguanine

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Activation of Ras signaling pathway by 8-oxoguanine DNA glycosylase bound to its excision product, 8-oxoguanine. / Boldogh, Istvan; Hajas, Gyorgy; Aguilera-Aguirre, Leopoldo; Hegde, Muralidhar L.; Radak, Zsolt; Bacsi, Attila; Sur, Sanjiv; Hazra, Tapas; Mitra, Sankar.

In: Journal of Biological Chemistry, Vol. 287, No. 25, 15.06.2012, p. 20769-20773.

Research output: Contribution to journalArticle

Boldogh, Istvan ; Hajas, Gyorgy ; Aguilera-Aguirre, Leopoldo ; Hegde, Muralidhar L. ; Radak, Zsolt ; Bacsi, Attila ; Sur, Sanjiv ; Hazra, Tapas ; Mitra, Sankar. / Activation of Ras signaling pathway by 8-oxoguanine DNA glycosylase bound to its excision product, 8-oxoguanine. In: Journal of Biological Chemistry. 2012 ; Vol. 287, No. 25. pp. 20769-20773.
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