Activation of Ras Signaling Pathway by 8-Oxoguanine DNA Glycosylase Bound to Its Excision Product, 8-Oxoguanine

Boldogh, István; Hajas, György; Aguilera-Aguirre, Leopoldo; Hegde, Muralidhar L.; Radák, Zsolt; Bácsi, Attila; Sur, Sanjiv; Hazra, Tapas K.; Mitra, Sankar

doi:10.1074/jbc.c112.364620

Cited by 110 publications

(149 citation statements)

References 28 publications

Supporting

Mentioning

138

Contrasting

Order By: Relevance

“…As compared with wild-type neuronal stem cells, loss of plasticity toward a terminally differentiated astrocytic lineage occurs in Ogg1-deficient neuronal stem cells that accumulate mtDNA damage (58). Ogg1 also has an emerging important role in linking DNA repair to Rac1 and Ras cellular signaling pathways (59,60). These findings support the notion that defects in Ogg1 and 8-oxoG DNA repair play an important role in enhancing mtDNA damage.…”

Section: Discussionsupporting

confidence: 78%

Mitochondria-targeted Ogg1 and Aconitase-2 Prevent Oxidant-induced Mitochondrial DNA Damage in Alveolar Epithelial Cells

Kim

Cheresh

Williams

et al. 2014

Journal of Biological Chemistry

View full text Add to dashboard Cite

Background: Mitochondrial Ogg1 prevents oxidant (H 2 O 2 and asbestos)-induced Aco-2 degradation and apoptosis. Results: Oxidant stress caused preferential AEC mtDNA Ͼ nuclear DNA damage, mt-p53 translocation, and apoptosis; effects were blocked by mt-hOgg1 or Aco-2. Conclusion: mt-hOgg1 and Aco-2 preserve AEC mtDNA, preventing oxidant-induced p53 activation and apoptosis. Significance: mt-hOgg1/Aco-2 effects on mtDNA may be an innovative target for preventing degenerative diseases.

show abstract

Section: Discussionsupporting

confidence: 78%

Mitochondria-targeted Ogg1 and Aconitase-2 Prevent Oxidant-induced Mitochondrial DNA Damage in Alveolar Epithelial Cells

Kim

Cheresh

Williams

et al. 2014

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…In mammals, the intra-helical 8-oxoG is recognized and excised by the E. coli Fpg homolog 8-oxoguanine DNA glycosylase 1 (OGG1) from nuclear and mitochondrial genome during base excision repair processes [19,20]. The resulting free 8-oxoG base is capable of binding to OGG1 with high affinity, and the complex then functions as an activator of Ras and Rho family GTPases contributing to oxidative stress related cellular responses [21][22][23]. Here, our aim was to investigate the consequence if 8-oxoG is not removed from mtDNA and the oxidatively modified mtDNA is released from the cells.…”

Section: Introductionmentioning

confidence: 99%

Oxidative modification enhances the immunostimulatory effects of extracellular mitochondrial DNA on plasmacytoid dendritic cells

Pázmándi

Agod

Kumar

et al. 2014

Free Radical Biology and Medicine

Self Cite

View full text Add to dashboard Cite

Oxidative modification enhances the immunostimulatory effects of extracellular mitochondrial DNA on plasmacytoid dendritic cells, Free Radical Biology and Medicine, http://dx.doi.org/10.1016/j. freeradbiomed. 2014.09.028 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting galley proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.www.elsevier.com/locate/freeradbiomed Abbreviations: 7-AAD, 7-aminoactinomycin-D; 8-oxoG, 8-oxo-7,8-dihydroguanine; 8-oxodG, 8-oxo-7,8-dihydro-2'- well as increased TNF-Į and IL-8 production from the cells. These effects were more apparent when pDCs were exposed to oxidatively modified mtDNA. Neither native nor oxidized mtDNA molecules were able to induce interferon (IFN)-Į secretion from pDCs unless they formed a complex with human cathelicidin LL-37, an antimicrobial peptide.Interestingly, simultaneous administration of a Toll-like receptor (TLR)9 antagonist abrogated the effects of both native and oxidized mtDNAs on human pDCs. In a murine model, oxidized mtDNA also proved a more potent activator of pDCs compared to the native form, except for induction of IFN-Į production. Collectively, we demonstrate here for the first time that elevated levels of 8-oxoG bases in the extracellular mtDNA induced by oxidative stress increase the immunostimulatory capacity of mtDNA on pDCs. 3 HighlightsWe compared the immunostimulatory capacity of native and oxidized mtDNA on pDCs.8-Oxoguanin-containing mtDNA has a greater capacity to activate primary human pDCs.In vivo, oxidized mtDNA also proved a more potent activator of pDC than native mtDNA.

show abstract

“…However, there is increasing evidence that by-products of DNA repair have the potential to impact cell signaling events (15)(16)(17)(18). Moreover, defects in the clearance of DNA oligonucleotides are associated with various autoimmune disorders (19 -21), and abnormal localization of DNA in the cytosol may be sensed by the innate immune system (22,23).…”

mentioning

confidence: 99%

DNA Repair Synthesis and Ligation Affect the Processing of Excised Oligonucleotides Generated by Human Nucleotide Excision Repair

Kemp

Gaddameedhi

Choi

et al. 2014

Journal of Biological Chemistry

View full text Add to dashboard Cite

Background:The mechanism of excised oligonucleotide processing during nucleotide excision repair is unknown. Results: UV photoproduct-containing oligonucleotides associate with chromatin following the dual incisions. Inhibition of gap-filling activities results in an accumulation of RPA-bound small, excised, damaged DNA (sedDNA) fragments. Conclusion: Gap filling-mediated dissociation of sedDNAs from RPA influences nucleotide excision repair rate. Significance: sedDNA processing is important in the DNA damage response.

show abstract

Activation of Ras Signaling Pathway by 8-Oxoguanine DNA Glycosylase Bound to Its Excision Product, 8-Oxoguanine

Cited by 110 publications

References 28 publications

Mitochondria-targeted Ogg1 and Aconitase-2 Prevent Oxidant-induced Mitochondrial DNA Damage in Alveolar Epithelial Cells

Mitochondria-targeted Ogg1 and Aconitase-2 Prevent Oxidant-induced Mitochondrial DNA Damage in Alveolar Epithelial Cells

Oxidative modification enhances the immunostimulatory effects of extracellular mitochondrial DNA on plasmacytoid dendritic cells

DNA Repair Synthesis and Ligation Affect the Processing of Excised Oligonucleotides Generated by Human Nucleotide Excision Repair

Contact Info

Product

Resources

About