The Characterization of Mip1 DNA Polymerase


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Mitochondria are the only organelle to possess their own DNA outside of the nucleus. A single polymerase is primarily responsible for the replication and repair of mtDNA. In humans and other animals, this enzyme is known as polymerase gamma (Pol γ) and it is orthologous to Mitochondrial DNA Polymerase 1 (Mip1) from Saccharomyces cerevisiae. Mutations in human Pol γ can cause diseases such as Alper’s Syndrome, external ophthalmoplegia (PEO), and other mitochondrial pathologies. Yeast has been used to analyze disease associated mutations in hPol γ by utilizing Mip1 as a model to determine the molecular defects leading to the disease phenotype. While Mip1 and hPol γ are orthologous, the Mip1 protein is a functional monomer possessing a unique C terminal extended (CTE) domain in contrast to hPol γ’s functional heterotrimer complex. In this thesis, I investigated the protein structure and mechanism of action of the CTE domain in replication, repair, and drug induced toxicity to further develop Mip1 as a model for hPol γ and mtDNA maintenance in general.



Mip1, Polymerase, mitochondria, mtDNA