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Intracellular Localization of 8-Oxo-dGTPase in Human Cells, with Special Reference to the Role of the Enzyme in Mitochondria
Open accessAbstract
We examined the intracellular distribution of 8-oxo-dGTPase (8-oxo-7,8-dihydrodeoxyguanosine triphosphatase) encoded by the MTH1 gene, a human mutator homologue. The activity of 8-oxo-dGTPase mainly located in cytosolic and mitochondrial soluble fractions of Jurkat cells, a human T-cell leukemia line. Electron microscopic immunocytochemistry, using a specific antibody against MTH1 protein, showed localization of MTH1 protein in the mitochondrial matrix. Activity in the mitochondria accounted for about 4% of the total activity. The specific activity in the mitochondrial soluble fraction (8093 units/mg protein) was as high as that in the cytosolic fraction (8111 unit/mg protein). The 8-oxo-dGTPase activities in cytosolic and mitochondrial soluble fractions co-eluted with MTH1 protein by anion-exchange chromatography, and the molecular mass of the mitochondrial MTH1 protein was much the same as that of the cytosolic MTH1 protein (about 18 kDa). HeLa cells expressing MTH1 cDNA showed an increased cytoplasmic signal together with a weak signal in the nucleus in in situ immunostaining of MTH1 protein, and the overexpressed MTH1 protein was recovered from both cytosolic and mitochondrial fractions. Thus, the 8-oxo-dGTPase encoded by MTH1 gene is localized in mitochondrial and cytosol.
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Cites
Insertion of specific bases during DNA synthesis past the oxidation-damaged base 8-oxodG
Shibutani, S., Takeshita, M., & Grollman, A. P. (1991) · Nature · doi:10.1038/349431a0 · Cited by 2,224
DNA replication fidelity with 8-oxodeoxyguanosine triphosphate
Pavlov, Y. I., Minnick, D. T., Izuta, S., & Kunkel, T. A. (1994) · Biochemistry · doi:10.1021/bi00181a029 · Cited by 132
Cited by
Oxidative DNA damage and disease: induction, repair and significance
Evans, M. D., Dizdaroglu, M., & Cooke, M. S. (2004) · Mutation Research/Reviews in Mutation Research · doi:10.1016/j.mrrev.2003.11.001 · Cited by 1,372
Mitochondrial biogenesis and mitochondrial DNA maintenance of mammalian cells under oxidative stress
Lee, H.-C., & Wei, Y.-H. (2005) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2004.09.010 · Cited by 666
Mammalian Mitochondria and Aging: An Update
Kauppila, T. E. S., Kauppila, J. H. K., & Larsson, N.-G. (2017) · Cell Metabolism · doi:10.1016/j.cmet.2016.09.017 · Cited by 578
The Maintenance of Mitochondrial DNA Integrity--Critical Analysis and Update
Alexeyev, M., Shokolenko, I., Wilson, G., & LeDoux, S. (2013) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a012641 · Cited by 458
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Alam, T. I. (2003) · Nucleic Acids Research · doi:10.1093/nar/gkg251 · Cited by 393
Metadata
- Authors
- Kang, D., Nishida, J.-I., Iyama, A., Nakabeppu, Y., Furuichi, M., Fujiwara, T., Sekiguchi, M., & Takeshige, K.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 1995-06
- Volume
- 270
- Issue
- 24
- Pages
- 14659-14665
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2060657842
- Cited by
- 187
- References
- 2
- FWCI
- 1.89
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- Kang, D., Nishida, J.-I., Iyama, A., Nakabeppu, Y., Furuichi, M., Fujiwara, T., Sekiguchi, M., & Takeshige, K. (1995). Intracellular Localization of 8-Oxo-dGTPase in Human Cells, with Special Reference to the Role of the Enzyme in Mitochondria. Journal of Biological Chemistry. https://doi.org/10.1074/jbc.270.24.14659
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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