DNA polymerase beta (POLβ), 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 POLβ and POLγ, the mitochondrial replicative polymerase, previously thought to be the only mitochondrial polymerase. We find that POLβ 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 POLβ 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 POLβ are severely deficient in processing BER intermediates, suggesting that mitochondrially localized DNA POLβ 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.

DNA聚合酶β（POLβ）以其在核DNA碱基切除修复（BER）中的作用而闻名，已被证明存在于几种不同细胞类型的线粒体中。在这里，我们对 POLβ 和 POLγ（线粒体复制聚合酶）的 BER 活性进行并排比较，以前被认为是唯一的线粒体聚合酶。我们发现 POLβ 在单核苷酸间隙填充方面明显更加熟练，无论是在末端需要聚合酶处理的底物中，还是不需要的底物中。我们还表明 POLβ 与线粒体解旋酶 TWINKLE 具有不依赖于解旋酶的功能相互作用。这种相互作用会刺激链置换合成，但不会刺激单核苷酸间隙填充。重要的，