The exonuclease activity of the yeast mitochondrial DNA polymerase γ suppresses mitochondrial DNA deletions between short direct repeats in Saccharomyces cerevisiae

Abstract

The importance of mitochondrial DNA (mtDNA) deletions in the progeroid phenotype of exonuclease-deficient DNA polymerase γ mice has been intensely debated. We show that disruption of Mip1 exonuclease activity increases mtDNA deletions 160fold, whereas disease-associated polymerase variants were mostly unaffected, suggesting that exonuclease activity is vital to avoid deletions during mtDNA replication. © 2013 by the Genetics Society of America.