Whole transcriptome analysis reveals an 8-oxoguanine DNA glycosylase-1-driven DNA repair-dependent gene expression linked to essential biological processes

Leopoldo Aguilera-Aguirre, Koa Hosoki, Attila Bacsi, Zsolt Radák, Thomas Wood, Steven Widen, Sanjiv Sur, Bill Ameredes, Alfredo Saavedra-Molina, Allan R. Brasier, Xueqing Ba, Istvan Boldogh

Research output: Contribution to journalArticle

23 Scopus citations

Abstract

Reactive oxygen species inflict oxidative modifications on various biological molecules, including DNA. One of the most abundant DNA base lesions, 8-oxo-7,8-dihydroguanine (8-oxoG) is repaired by 8-oxoguanine DNA glycosylase-1 (OGG1) during DNA base excision repair (OGG1-BER). 8-OxoG accumulation in DNA has been associated with various pathological and aging processes, although its role is unclear. The lack of OGG1-BER in Ogg1-/- mice resulted in decreased inflammatory responses and increased susceptibility to infections and metabolic disorders. Therefore, we proposed that OGG1 and/or 8-oxoG base may have a role in immune and homeostatic processes. To test our hypothesis, we challenged mouse lungs with OGG1-BER product 8-oxoG base and changes in gene expression were determined by RNA sequencing and data were analyzed by Gene Ontology and statistical tools. RNA-Seq analysis identified 1592 differentially expressed (≥ 3-fold change) transcripts. The upregulated mRNAs were related to biological processes, including homeostatic, immune-system, macrophage activation, regulation of liquid-surface tension, and response to stimulus. These processes were mediated by chemokines, cytokines, gonadotropin-releasing hormone receptor, integrin, and interleukin signaling pathways. Taken together, these findings point to a new paradigm showing that OGG1-BER plays a role in various biological processes that may benefit the host, but when in excess could be implicated in disease and/or aging processes.

Original languageEnglish (US)
Pages (from-to)107-118
Number of pages12
JournalFree Radical Biology and Medicine
Volume81
DOIs
StatePublished - 2015

    Fingerprint

Keywords

  • 8-Oxoguanine
  • Biological processes
  • Gene expression
  • OGG1-BER

ASJC Scopus subject areas

  • Biochemistry
  • Physiology (medical)

Cite this