The Role of the MRX Complex and the Non-homologous End Joining DNA Repair Pathway in Mitochondrial Genome Stability and Repair

Abstract

Mitochondria are required for cellular respiration, which is essential in the production of ATP. Mitochondrial genome maintenance is necessary for the continued function of the mitochondrion. Deletions within the mitochondrial DNA (mtDNA) have been shown to be associated with a variety of human neuromuscular and age-related diseases. In this study we investigated the role of the MRX complex and the non-homologous end joining (NHEJ) DNA repair pathway in mitochondrial genome stability and repair. Specifically, we investigated the role of the MRX complex and the NHEJ pathway in the occurrence of spontaneous mitochondrial direct repeat-mediated deletions, nuclear direct repeat-mediated deletions, mitochondrial point mutations, nuclear point mutations, and spontaneous respiration loss using fluctuation analysis in the budding yeast, Saccharomyces cerevisiae. In this study, we have demonstrated that spontaneous mitochondrial direct repeat-mediated deletions are reduced 75 fold (p