1. Mechanisms of replication and repair in mitochondrial DNA deletion formation.
- Author
-
Fontana GA and Gahlon HL
- Subjects
- DNA Breaks, Double-Stranded, DNA Mismatch Repair, DNA, Mitochondrial metabolism, Genetic Diseases, Inborn metabolism, Humans, Mitochondria pathology, Mitochondrial Diseases metabolism, Oxidative Phosphorylation, Sequence Deletion, DNA Repair, DNA Replication, DNA, Mitochondrial biosynthesis, Genetic Diseases, Inborn genetics, Mitochondria genetics, Mitochondrial Diseases genetics
- Abstract
Deletions in mitochondrial DNA (mtDNA) are associated with diverse human pathologies including cancer, aging and mitochondrial disorders. Large-scale deletions span kilobases in length and the loss of these associated genes contributes to crippled oxidative phosphorylation and overall decline in mitochondrial fitness. There is not a united view for how mtDNA deletions are generated and the molecular mechanisms underlying this process are poorly understood. This review discusses the role of replication and repair in mtDNA deletion formation as well as nucleic acid motifs such as repeats, secondary structures, and DNA damage associated with deletion formation in the mitochondrial genome. We propose that while erroneous replication and repair can separately contribute to deletion formation, crosstalk between these pathways is also involved in generating deletions., (© The Author(s) 2020. Published by Oxford University Press on behalf of Nucleic Acids Research.)
- Published
- 2020
- Full Text
- View/download PDF