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 Citations (Scopus)

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

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DNA Glycosylases
Biological Phenomena
Gene Expression Profiling
Gene expression
DNA Repair
Repair
Gene Expression
DNA
Aging of materials
RNA
LHRH Receptors
RNA Sequence Analysis
Gene Ontology
Surface Tension
Macrophage Activation
Macrophages
Immune system
Interleukins
Pathologic Processes
Chemokines

Keywords

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

ASJC Scopus subject areas

  • Biochemistry
  • Physiology (medical)

Cite this

Whole transcriptome analysis reveals an 8-oxoguanine DNA glycosylase-1-driven DNA repair-dependent gene expression linked to essential biological processes. / Aguilera-Aguirre, Leopoldo; Hosoki, Koa; Bacsi, Attila; Radák, Zsolt; Wood, Thomas; Widen, Steven; Sur, Sanjiv; Ameredes, Bill; Saavedra-Molina, Alfredo; Brasier, Allan R.; Ba, Xueqing; Boldogh, Istvan.

In: Free Radical Biology and Medicine, Vol. 81, 2015, p. 107-118.

Research output: Contribution to journalArticle

Aguilera-Aguirre, Leopoldo ; Hosoki, Koa ; Bacsi, Attila ; Radák, Zsolt ; Wood, Thomas ; Widen, Steven ; Sur, Sanjiv ; Ameredes, Bill ; Saavedra-Molina, Alfredo ; Brasier, Allan R. ; Ba, Xueqing ; Boldogh, Istvan. / Whole transcriptome analysis reveals an 8-oxoguanine DNA glycosylase-1-driven DNA repair-dependent gene expression linked to essential biological processes. In: Free Radical Biology and Medicine. 2015 ; Vol. 81. pp. 107-118.
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AU - Radák, Zsolt

AU - Wood, Thomas

AU - Widen, Steven

AU - Sur, Sanjiv

AU - Ameredes, Bill

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AU - Boldogh, Istvan

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