DNA Polymerase ? Increases Mutational Rates in Mitochondrial DNA.

ABSTRACT: Replication and maintenance of mitochondrial DNA (mtDNA) is essential for cellular function, yet few DNA polymerases are known to function in mitochondria. Here, we conclusively demonstrate that DNA polymerase ? (Pol?) localizes to mitochondria and explore whether this protein is overexpressed in patient-derived cells and tumors. Pol? appears to play an important role in facilitating mtDNA replication under conditions of oxidative stress, and this error-prone polymerase was found to introduce mutations into mtDNA. In patient-derived cells bearing a pathogenic mtDNA mutation, Pol? expression levels were increased, indicating that the oxidative conditions in these cells promote higher expression levels for Pol?. Heightened Pol? expression levels were also associated with elevated mtDNA mutation rates in a selected panel of human tumor tissues, suggesting that this protein can influence mutational frequencies in tumors. The results reported indicate that the mitochondrial function of Pol? may have relevance to human disease.

SUBMITTER: Wisnovsky S 

PROVIDER: S-EPMC5914477 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature