Innate inflammation induced by the 8-oxoguanine DNA glycosylase-1-KRAS-NF-κB pathway.

ABSTRACT: 8-Oxoguanine-DNA glycosylase-1 (OGG1) is the primary enzyme for repairing 7,8-dihydro-8-oxoguanine (8-oxoG) via the DNA base excision repair pathway (OGG1-BER). Accumulation of 8-oxoG in the genomic DNA leads to genetic instability and carcinogenesis and is thought to contribute to the worsening of various inflammatory and disease processes. However, the disease mechanism is unknown. In this study, we proposed that the mechanistic link between OGG1-BER and proinflammatory gene expression is OGG1's guanine nucleotide exchange factor activity, acquired after interaction with the 8-oxoG base and consequent activation of the small GTPase RAS. To test this hypothesis, we used BALB/c mice expressing or deficient in OGG1 in their airway epithelium and various molecular biological approaches, incl

SUBMITTER: Aguilera-Aguirre L 

PROVIDER: S-EPMC4201976 | biostudies-literature | 2014 Nov

REPOSITORIES: biostudies-literature