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

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...

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Detalles Bibliográficos
Autores principales: Ling, Feng, Yoshida, Minoru
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7288456/
https://www.ncbi.nlm.nih.gov/pubmed/32384722
http://dx.doi.org/10.3390/genes11050514
Descripción
Sumario: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.