title: Whole transcriptome analysis reveals an 8-oxoguanine DNA glycosylase-1-driven DNA repair-dependent gene expression linked to essential biological processes.
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.
authors.affiliation: Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555, USA.
authors.forename: Leopoldo
authors.initials: L
authors.lastname: Aguilera-Aguirre
authors.affiliation: Department of Internal Medicine, University of Texas Medical Branch, Galveston, TX 77555, USA.
authors.forename: Koa
authors.initials: K
authors.lastname: Hosoki
authors.affiliation: Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555, USA.
authors.forename: Attila
authors.initials: A
authors.lastname: Bacsi
authors.affiliation: Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555, USA.
authors.forename: Zsolt
authors.initials: Z
authors.lastname: Radák
authors.affiliation: Sealy Center for Molecular Medicine, University of Texas Medical Branch, Galveston, TX 77555, USA; Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, TX 77555, USA.
authors.forename: Thomas G
authors.initials: TG
authors.lastname: Wood
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, TX 77555, USA.
authors.forename: Steven G
authors.initials: SG
authors.lastname: Widen
authors.affiliation: Department of Internal Medicine, University of Texas Medical Branch, Galveston, TX 77555, USA; Sealy Center for Molecular Medicine, University of Texas Medical Branch, Galveston, TX 77555, USA.
authors.forename: Sanjiv
authors.initials: S
authors.lastname: Sur
authors.affiliation: Department of Internal Medicine, University of Texas Medical Branch, Galveston, TX 77555, USA.
authors.forename: Bill T
authors.initials: BT
authors.lastname: Ameredes
authors.affiliation: Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555, USA.
authors.forename: Alfredo
authors.initials: A
authors.lastname: Saavedra-Molina
authors.affiliation: Department of Internal Medicine, University of Texas Medical Branch, Galveston, TX 77555, USA; Sealy Center for Molecular Medicine, University of Texas Medical Branch, Galveston, TX 77555, USA.
authors.forename: Allan R
authors.initials: AR
authors.lastname: Brasier
authors.affiliation: Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555, USA.
authors.forename: Xueqing
authors.initials: X
authors.lastname: Ba
authors.affiliation: Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555, USA; Sealy Center for Molecular Medicine, University of Texas Medical Branch, Galveston, TX 77555, USA. Electronic address: sboldogh@utmb.edu.
authors.forename: Istvan
authors.initials: I
authors.lastname: Boldogh
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D004247:DNA / Q000235:genetics* / Q000378:metabolism; D045647:DNA Glycosylases / Q000172:deficiency / Q000235:genetics*; D004260:DNA Repair; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006147:Guanine / Q000008:administration & dosage / Q000031:analogs & derivatives; D008168:Lung / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D053858:Metabolic Networks and Pathways / Q000235:genetics / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D058977:Molecular Sequence Annotation; D018384:Oxidative Stress; D011014:Pneumonia / Q000139:chemically induced / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction; D059467:Transcriptome
chemical_list: C453560:7,8-dihydro-8-oxoguanine; D017382:Reactive Oxygen Species; D006147:Guanine; D004247:DNA; D045647:DNA Glycosylases; C485990:Ogg1 protein, mouse
keywords: 8-Oxoguanine; Biological processes; Gene expression; OGG1-BER