Oxidative DNA damage has been attributed to increased cancer incidence and premature aging phenotypes. Reactive oxygen species (ROS) are unavoidable byproducts of oxidative phosphorylation and are the major contributors of endogenous oxidative damage. To prevent the negative effects of ROS, cells have developed DNA repair mechanisms designed to specifically combat endogenous DNA modifications. The base excision repair (BER) pathway is primarily responsible for the repair of small non-helix distorting lesions and DNA single strand breaks. This repair pathway is found in all organisms, and in mammalian cells, consists of three related sub-pathways: short patch (SP-BER), long patch (LP-BER) and single strand break repair (SSBR). While much is known about nuclear BER, comparatively little is known about this pathway in the mitochondria, particularly the LP-BER and SSBR sub-pathways. There are a number of proteins that have recently been found to be involved in mitochondrial BER, including Cockayne syndrome proteins A and B (CSA and CSB), aprataxin (APTX), tryosyl-DNA phosphodiesterase 1 (TDP1), flap endonuclease 1 (FEN-1) and exonuclease G (EXOG). These significant advances in mitochondrial DNA repair may open new avenues in the management and treatment of a number of neurological disorders associated with mitochondrial dysfunction, and will be reviewed in further detail herein.

中文翻译：

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修复线粒体基因组中的持久链断裂。

氧化性 DNA 损伤归因于癌症发病率增加和过早老化表型。活性氧 (ROS) 是氧化磷酸化不可避免的副产物，是内源性氧化损伤的主要贡献者。为了防止 ROS 的负面影响，细胞开发了 DNA 修复机制，旨在专门对抗内源性 DNA 修饰。碱基切除修复 (BER) 途径主要负责修复小的非螺旋扭曲损伤和 DNA 单链断裂。这种修复途径存在于所有生物体和哺乳动物细胞中，由三个相关的子途径组成：短补丁 (SP-BER)、长补丁 (LP-BER) 和单链断裂修复 (SSBR)。虽然对核 BER 了解很多，但对线粒体中的这条通路知之甚少，特别是 LP-BER 和 SSBR 子路径。最近发现许多蛋白质与线粒体 BER 有关，包括 Cockayne 综合征蛋白质 A 和 B（CSA 和 CSB）、aprataxin (APTX)、酪氨酰 DNA 磷酸二酯酶 1 (TDP1)、皮瓣核酸内切酶 1 (FEN) -1) 和外切核酸酶 G (EXOG)。线粒体 DNA 修复方面的这些重大进展可能为与线粒体功能障碍相关的许多神经系统疾病的管理和治疗开辟新途径，本文将对其进行更详细的综述。