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Rolling-Circle Replication in Mitochondrial DNA Inheritance: Scientific Evidence and Significance from Yeast to Human Cells

by Feng Ling 1,* and Minoru Yoshida 1,2,3,4
1
Chemical Genetics Research Group, RIKEN Center for Sustainable Resource Science, Hirosawa 2-1, Wako, Saitama 351-0198, Japan
2
Graduate School of Science and Engineering, Saitama University, Saitama 338-8570, Japan
3
Department of Biotechnology, Graduate School of Agricultural Life Sciences, the University of Tokyo, Tokyo 113-8657, Japan
4
Collaborative Research Institute for Innovative Microbiology, the University of Tokyo, Tokyo 113-8657, Japan
*
Author to whom correspondence should be addressed.
Genes 2020, 11(5), 514; https://doi.org/10.3390/genes11050514
Received: 2 April 2020 / Revised: 29 April 2020 / Accepted: 29 April 2020 / Published: 6 May 2020
(This article belongs to the Special Issue Genetic Aspects of Yeast: Cell Biology, Ecology and Biotechnology)
Studies of mitochondrial (mt)DNA replication, which forms the basis of mitochondrial inheritance, have demonstrated that a rolling-circle replication mode exists in yeasts and human cells. In yeast, rolling-circle mtDNA replication mediated by homologous recombination is the predominant pathway for replication of wild-type mtDNA. In human cells, reactive oxygen species (ROS) induce rolling-circle replication to produce concatemers, linear tandem multimers linked by head-to-tail unit-sized mtDNA that promote restoration of homoplasmy from heteroplasmy. The event occurs ahead of mtDNA replication mechanisms observed in mammalian cells, especially under higher ROS load, as newly synthesized mtDNA is concatemeric in hydrogen peroxide-treated human cells. Rolling-circle replication holds promise for treatment of mtDNA heteroplasmy-attributed diseases, which are regarded as incurable. This review highlights the potential therapeutic value of rolling-circle mtDNA replication. View Full-Text
Keywords: homologous recombination; rolling-circle replication; concatemers; oxidative stress; homoplasmy; heteroplasmy homologous recombination; rolling-circle replication; concatemers; oxidative stress; homoplasmy; heteroplasmy
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Ling, F.; Yoshida, M. Rolling-Circle Replication in Mitochondrial DNA Inheritance: Scientific Evidence and Significance from Yeast to Human Cells. Genes 2020, 11, 514.

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