Zinovkina L A
Lomonosov Moscow State University, Faculty of Bioengineering and Bioinformatics, Moscow, 119234, Russia.
Biochemistry (Mosc). 2018 Mar;83(3):233-249. doi: 10.1134/S0006297918030045.
Accumulation of mutations in mitochondrial DNA leads to the development of severe, currently untreatable diseases. The contribution of these mutations to aging and progress of neurodegenerative diseases is actively studied. Elucidation of DNA repair mechanisms in mitochondria is necessary for both developing approaches to the therapy of diseases caused by mitochondrial mutations and understanding specific features of mitochondrial genome functioning. Mitochondrial DNA repair systems have become a subject of extensive studies only in the last decade due to development of molecular biology methods. DNA repair systems of mammalian mitochondria appear to be more diverse and effective than it had been thought earlier. Even now, one may speak about the existence of mitochondrial mechanisms for the repair of single- and double-stranded DNA lesions. Homologous recombination also takes place in mammalian mitochondria, although its functional significance and molecular mechanisms remain obscure. In this review, I describe DNA repair systems in mammalian mitochondria, such as base excision repair (BER) and microhomology-mediated end joining (MMEJ) and discuss a possibility of existence of mitochondrial DNA repair mechanisms otherwise typical for the nuclear DNA, e.g., nucleotide excision repair (NER), mismatch repair (MMR), homologous recombination, and classical non-homologous end joining (NHEJ). I also present data on the mechanisms for coordination of the nuclear and mitochondrial DNA repair systems that have been actively studied recently.
线粒体DNA中的突变积累会导致严重的、目前无法治疗的疾病的发生。这些突变对衰老和神经退行性疾病进展的影响正在被积极研究。阐明线粒体中的DNA修复机制对于开发治疗线粒体突变引起的疾病的方法以及理解线粒体基因组功能的特定特征都是必要的。由于分子生物学方法的发展，线粒体DNA修复系统只是在过去十年才成为广泛研究的对象。哺乳动物线粒体的DNA修复系统似乎比之前认为的更加多样和有效。即使在现在，人们也可以说存在修复单链和双链DNA损伤的线粒体机制。同源重组也在哺乳动物线粒体中发生，尽管其功能意义和分子机制仍不清楚。在这篇综述中，我描述了哺乳动物线粒体中的DNA修复系统，如碱基切除修复（BER）和微同源性介导的末端连接（MMEJ），并讨论了线粒体中存在其他典型的核DNA修复机制的可能性，例如核苷酸切除修复（NER）、错配修复（MMR）、同源重组和经典的非同源末端连接（NHEJ）。我还展示了最近被积极研究的核DNA和线粒体DNA修复系统协调机制的数据。
