Skip Navigation

Publication Detail

Title: Activation of ras signaling pathway by 8-oxoguanine DNA glycosylase bound to its excision product, 8-oxoguanine.

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

Published In J Biol Chem, (2012 Jun 15)

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.

PubMed ID: 22568941 Exiting the NIEHS site

MeSH Terms: DNA Glycosylases/genetics; DNA Glycosylases/metabolism*; DNA Repair/physiology*; Fibroblasts/cytology; Fibroblasts/metabolism*; Genome, Human/physiology; Guanine/analogs & derivatives*; Guanine/metabolism; Guanosine Diphosphate/genetics; Guanosine Diphosphate/metabolism; Guanosine Triphosphate/genetics; Guanosine Triphosphate/metabolism; HeLa Cells; Humans; MAP Kinase Signaling System/physiology*; Mitogen-Activated Protein Kinase Kinases/genetics; Mitogen-Activated Protein Kinase Kinases/metabolism*; Phosphorylation/physiology; ras Proteins/genetics; ras Proteins/metabolism*

Back
to Top