DNA polymerase beta participates in mitochondrial DNA repair.

ABSTRACT: We have detected DNA polymerase beta (Pol?), known as a key nuclear base excision repair (BER) protein, in mitochondrial protein extracts derived from mammalian tissue and cells. Manipulation of the N-terminal sequence affected the amount of Pol? in the mitochondria. Using Pol? fragments, mitochondrial-specific protein partners were identified, with the interactors mainly functioning in DNA maintenance and mitochondrial import. Of particular interest was the identification of the proteins TWINKLE, SSBP1 and TFAM, all of which are mitochondria specific DNA effectors and are known to function in the nucleoid. Pol? directly interacted with, and influenced the activity of, the mitochondrial helicase TWINKLE. Human kidney cells with Pol? knock-out (KO) had higher endogenous mtDNA damage. Mitochondrial extracts derived from heterozygous Pol? mouse tissue and KO cells had lower nucleotide incorporation activity. Mouse derived Pol? null fibroblasts had severely affected metabolic parameters. Indeed, gene knockout of Pol? caused mitochondrial dysfunction including reduced membrane potential and mitochondrial content. We show that Pol? is a mitochondrial polymerase involved in mtDNA maintenance and is required for mitochondrial homeostasis.

SUBMITTER: Sykora P 

PROVIDER: S-EPMC5533889 | biostudies-other | 2017 May

REPOSITORIES: biostudies-other