Journal
DNA REPAIR
Volume 60, Issue -, Pages 77-88Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.dnarep.2017.10.011
Keywords
Mitochondria DNA polymerase beta; DNA polymerase gamma; Base excision repair; Electron microscopy; Immunogold staining; Confocal immunofluorescence microscopy
Categories
Funding
- Intramural Research Program of the National Institutes of Health, National Institute of Environmental Health Sciences [Z01ES050158, Z01ES050159, Z01ES065078, R00ES023813]
- NIH [GM31819, ES13773]
Ask authors/readers for more resources
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) beta. Pol beta 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 beta. Mitochondria from pol beta-deficient mouse fibroblasts had compromised DNA repair and showed elevated levels of superoxide radicals after hydrogen peroxide treatment. Mitochondria in pol beta-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 poi beta and thus pol beta plays a role in preserving mitochondrial genome stability.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available