Mitochondrial Genome Maintenance: Roles for Nuclear Nonhomologous End-Joining Proteins in Saccharomyces cerevisiae
| Autor: | Daniel F Quintana, Lidza Kalifa, Garry L Coles, Laura K Schiraldi, Rey A. L. Sia, Naina Phadnis, Elaine A. Sia |
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| Rok vydání: | 2012 |
| Předmět: |
Mitochondrial DNA
DNA End-Joining Repair Saccharomyces cerevisiae Proteins DNA Repair Saccharomyces cerevisiae Investigations Biology DNA Mitochondrial Human mitochondrial genetics Genome Mutation Rate Gene Order Genetics DNA Breaks Double-Stranded Deoxyribonucleases Type II Site-Specific Ku Autoantigen Repetitive Sequences Nucleic Acid Sequence Deletion Cell Nucleus Recombination Genetic mtDNA control region Endodeoxyribonucleases Models Genetic Mitochondrial genome maintenance Nuclear Proteins Antigens Nuclear Mitochondria DNA-Binding Proteins Non-homologous end joining Exodeoxyribonucleases Phenotype mitochondrial fusion Genome Mitochondrial Homologous recombination Signal Transduction |
| Zdroj: | Genetics. 190:951-964 |
| ISSN: | 1943-2631 |
| Popis: | Mitochondrial DNA (mtDNA) deletions are associated with sporadic and inherited diseases and age-associated neurodegenerative disorders. Approximately 85% of mtDNA deletions identified in humans are flanked by short directly repeated sequences; however, mechanisms by which these deletions arise are unknown. A limitation in deciphering these mechanisms is the essential nature of the mitochondrial genome in most living cells. One exception is budding yeast, which are facultative anaerobes and one of the few organisms for which directed mtDNA manipulation is possible. Using this model system, we have developed a system to simultaneously monitor spontaneous direct-repeat–mediated deletions (DRMDs) in the nuclear and mitochondrial genomes. In addition, the mitochondrial DRMD reporter contains a unique KpnI restriction endonuclease recognition site that is not present in otherwise wild-type (WT) mtDNA. We have expressed KpnI fused to a mitochondrial localization signal to induce a specific mitochondrial double-strand break (mtDSB). Here we report that loss of the MRX (Mre11p, Rad50p, Xrs2p) and Ku70/80 (Ku70p, Ku80p) complexes significantly impacts the rate of spontaneous deletion events in mtDNA, and these proteins contribute to the repair of induced mtDSBs. Furthermore, our data support homologous recombination (HR) as the predominant pathway by which mtDNA deletions arise in yeast, and suggest that the MRX and Ku70/80 complexes are partially redundant in mitochondria. |
| Databáze: | OpenAIRE |
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