Document Detail

Essential role of β-human 8-oxoguanine DNA glycosylase 1 in mitochondrial oxidative DNA repair.
MedLine Citation:
PMID:  23055259     Owner:  NLM     Status:  MEDLINE    
8-Oxoguanine (8-OG) is the major mutagenic base lesion in DNA caused by reactive oxygen species (ROS) and accumulates in both nuclear and mitochondrial DNA (mtDNA). In humans, 8-OG is primarily removed by human 8-OG DNA glycosylase 1 (hOGG1) through the base excision repair (BER) pathway. There are two major hOGG1 isoforms, designated α- and β-hOGG1, generated by alternative splicing, and they have distinct subcellular localization: cell nuclei and mitochondria, respectively. Using yeast two-hybrid screening assays, we found that β- but not α-hOGG1 directly interacts with the mitochondrial protein NADH:ubiquinone oxidoreductase 1 beta subcomplex 10 (NDUFB10), an integral factor in Complex 1 on the mitochondrial inner membrane. Using coimmunoprecipitation and immunofluorescence studies, we found that this interaction was greatly increased by hydrogen peroxide-induced oxidative stress, suggesting that β- but not α-hOGG1 is localized in the mitochondrial inner membrane. Analyses of nuclear and mtDNA damage showed that the β- but not α- hogg1 knockdown (KD) cells were severely defective in mitochondrial BER, indicating an essential requirement of β-hOGG1 for mtDNA repair. β-hogg1 KD cells were also found to be mildly deficient in Complex I activity, suggesting that β-hOGG1 is an accessory factor for the mitochondrial integral function for ATP synthesis. In summary, our findings define β-hOGG1 as an important factor for mitochondrial BER and as an accessory factor in the mitochondrial Complex I function.
Yu-Hung Su; Yen-Ling Lee; Sung-Fang Chen; Yun-Ping Lee; Yi-Hsuan Hsieh; Jui-He Tsai; Jye-Lin Hsu; Wei-Ting Tian; Wenya Huang
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-10-11
Journal Detail:
Title:  Environmental and molecular mutagenesis     Volume:  54     ISSN:  1098-2280     ISO Abbreviation:  Environ. Mol. Mutagen.     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-01-03     Completed Date:  2013-04-19     Revised Date:  2014-03-14    
Medline Journal Info:
Nlm Unique ID:  8800109     Medline TA:  Environ Mol Mutagen     Country:  United States    
Other Details:
Languages:  eng     Pagination:  54-64     Citation Subset:  IM    
Copyright Information:
Copyright © 2012 Wiley Periodicals, Inc.
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MeSH Terms
Cell Nucleus / genetics
DNA Glycosylases / genetics,  metabolism*
DNA Repair*
DNA, Mitochondrial / genetics,  metabolism*
Electron Transport Complex I / genetics,  metabolism
NADH Dehydrogenase / genetics
Oxidative Stress
Grant Support
100140//Wellcome Trust
Reg. No./Substance:
0/DNA, Mitochondrial; EC protein, human; EC Transport Complex I; EC Dehydrogenase; EC 3.2.2.-/DNA Glycosylases; EC 3.2.2.-/oxoguanine glycosylase 1, human

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