DNA polymerase β: A missing link of the base excision repair machinery in mammalian mitochondria
| Autor: | Ming-Lang Zhao, Rachel Krasich, William C. Copeland, Matthew J. Longley, Donna F. Stefanick, Cristina A. Nadalutti, Rajendra Prasad, Agnes K. Janoshazi, Natalie R. Gassman, Julie K. Horton, Da-Peng Dai, Melike Çağlayan, Jack D. Griffith, Samuel H. Wilson |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Mitochondrial DNA DNA Repair DNA polymerase DNA damage DNA repair DNA polymerase beta DNA Mitochondrial Biochemistry DNA polymerase delta Article Mitochondrial Proteins Gene Knockout Techniques Mice 03 medical and health sciences chemistry.chemical_compound Superoxides Animals Humans Molecular Biology DNA Polymerase beta 030102 biochemistry & molecular biology biology Hydrogen Peroxide Cell Biology Base excision repair Fibroblasts Molecular biology Mitochondria Cell biology Oxidative Stress HEK293 Cells 030104 developmental biology chemistry biology.protein DNA Damage HeLa Cells Nucleotide excision repair |
| Zdroj: | DNA Repair. 60:77-88 |
| ISSN: | 1568-7864 |
| DOI: | 10.1016/j.dnarep.2017.10.011 |
| Popis: | Mitochondrial genome integrity is fundamental to mammalian cell viability. Since mitochondrial DNA is constantly under attack from oxygen radicals released during ATP production, DNA repair is vital in removing oxidatively generated lesions in mitochondrial DNA, but the presence of a strong base excision repair system has not been demonstrated. Here, we addressed the presence of such a system in mammalian mitochondria involving the primary base lesion repair enzyme DNA polymerase (pol) β. Pol β was localized to mammalian mitochondria by electron microscopic-immunogold staining, immunofluorescence co-localization and biochemical experiments. Extracts from purified mitochondria exhibited base excision repair activity that was dependent on pol β. Mitochondria from pol β-deficient mouse fibroblasts had compromised DNA repair and showed elevated levels of superoxide radicals after hydrogen peroxide treatment. Mitochondria in pol β-deficient fibroblasts displayed altered morphology by electron microscopy. These results indicate that mammalian mitochondria contain an efficient base lesion repair system mediated in part by pol β and thus pol β plays a role in preserving mitochondrial genome stability. |
| Databáze: | OpenAIRE |
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