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

*この研究の対応する著者

研究成果: Article査読

91 被引用数 (Scopus)

抄録

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.

本文言語English
ページ(範囲)20769-20773
ページ数5
ジャーナルJournal of Biological Chemistry
287
25
DOI
出版ステータスPublished - 2012 6 15
外部発表はい

ASJC Scopus subject areas

  • 生化学
  • 分子生物学
  • 細胞生物学

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