DNA polymerase β outperforms DNA polymerase γ in key mitochondrial base excision repair activities

DNA polymerase beta (POL beta), well known for its role in nuclear DNA base excision repair (BER), has been shown to be present in the mitochondria of several different cell types. Here we present a side-by-side comparison of BER activities of POL beta and POL gamma, the mitochondrial replicative polymerase, previously thought to be the only mitochondrial polymerase. We find that POL beta is significantly more proficient at single-nucleotide gap filling, both in substrates with ends that require polymerase processing, and those that do not. We also show that POL beta has a helicase-independent functional interaction with the mitochondrial helicase, TWINKLE. This interaction stimulates strand-displacement synthesis, but not single-nucleotide gap filling. Importantly, we find that purified mitochondrial extracts from cells lacking POL beta are severely deficient in processing BER intermediates, suggesting that mitochondrially localized DNA POL beta may be critical for cells with high energetic demands that produce greater levels of oxidative stress and therefore depend upon efficient BER for mitochondrial health.

Automated summary

The study reveals the presence of DNA polymerase beta (POL beta) in the mitochondria of various cell types, and demonstrates its superior efficiency in single-nucleotide gap filling compared to POL gamma. Additionally, POL beta shows a functional interaction with the mitochondrial helicase TWINKLE, promoting strand-displacement synthesis.