Kaufman Brett A, Van Houten Bennett
Center for Metabolism and Mitochondrial Medicine, Division of Cardiology, Vascular Medicine Institute, University of Pittsburgh School of Medicine, Pittsburgh PA USA.
Hillman Cancer Center, Department of Pharmacology and Chemical Biology, University of Pittsburgh Cancer Institute, Pittsburgh PA USA.
DNA Repair (Amst). 2017 Dec;60:A1-A5. doi: 10.1016/j.dnarep.2017.11.002. Epub 2017 Nov 6.
The mitochondrial genome is a matrilineally inherited DNA that encodes numerous essential subunits of the respiratory chain in all metazoans. As such mitochondrial DNA (mtDNA) sequence integrity is vital to organismal survival, but it has a limited cadre of DNA repair activities, primarily base excision repair (BER). We have known that the mtDNA is significantly oxidized by both endogenous and exogenous sources, but this does not lead to the expected preferential formation of transversion mutations, which suggest a robust base excision repair (BER) system. This year, two different groups reported compelling evidence that what was believed to be exclusively nuclear DNA repair polymerase, POLB, is located in the mitochondria and plays a significant role in mitochondrial BER, mtDNA integrity and mitochondrial function. In this commentary, we review the findings and highlight remaining questions for the field.
线粒体基因组是一种母系遗传的DNA，它编码所有后生动物呼吸链的众多重要亚基。因此，线粒体DNA（mtDNA）序列的完整性对生物体的生存至关重要，但它具有有限的DNA修复活性，主要是碱基切除修复（BER）。我们已经知道，mtDNA会被内源性和外源性来源显著氧化，但这并不会导致预期的颠换突变的优先形成，这表明存在一个强大的碱基切除修复（BER）系统。今年，两个不同的研究小组报告了令人信服的证据，即被认为仅存在于细胞核中的DNA修复聚合酶POLB位于线粒体中，并在线粒体BER、mtDNA完整性和线粒体功能中发挥重要作用。在这篇评论中，我们回顾了这些发现，并强调了该领域仍然存在的问题。
