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

研究成果: Article

82 引用 (Scopus)

抜粋

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.

元の言語English
ページ(範囲)20769-20773
ページ数5
ジャーナルJournal of Biological Chemistry
287
発行部数25
DOI
出版物ステータスPublished - 2012 6 15
外部発表Yes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Boldogh, I., Hajas, G., Aguilera-Aguirre, L., Hegde, M. L., Radak, Z., Bacsi, A., Sur, S., Hazra, T. K., & Mitra, S. (2012). Activation of Ras signaling pathway by 8-oxoguanine DNA glycosylase bound to its excision product, 8-oxoguanine. Journal of Biological Chemistry, 287(25), 20769-20773. https://doi.org/10.1074/jbc.C112.364620