| Essential role of β-human 8-oxoguanine DNA glycosylase 1 in mitochondrial oxidative DNA repair. | |
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MedLine Citation:
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PMID: 23055259 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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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. Mol. Mutagen. 2012. © 2012 Wiley Periodicals, Inc. |
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Authors:
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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:
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Type: JOURNAL ARTICLE Date: 2012-10-11 |
Journal Detail:
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Title: Environmental and molecular mutagenesis Volume: - ISSN: 1098-2280 ISO Abbreviation: Environ. Mol. Mutagen. Publication Date: 2012 Oct |
Date Detail:
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Created Date: 2012-10-11 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8800109 Medline TA: Environ Mol Mutagen Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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Copyright © 2012 Wiley Periodicals, Inc. |
Affiliation:
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Department of Medical Laboratory Science and Biotechnology, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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