Overexpression of DNA Polymerase Zeta Reduces the Mitochondrial Mutability Caused by Pathological Mutations in DNA Polymerase Gamma in Yeast

• Published in: PloS one Vol. 7; no. 3; p. e34322
• Main Authors: Baruffini, Enrico, Serafini, Fausta, Ferrero, Iliana, Lodi, Tiziana
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 28.03.2012; Public Library of Science (PLoS)
• Subjects: Baking yeast; Biology; Cell cycle; Deoxyribonucleic acid; DNA; DNA biosynthesis; DNA polymerase; DNA Polymerase gamma; DNA Polymerase I - genetics; DNA Polymerase I - metabolism; DNA polymerases; DNA, Mitochondrial - metabolism; DNA-directed DNA polymerase; DNA-Directed DNA Polymerase - genetics; DNA-Directed DNA Polymerase - metabolism; Evolution; Gene Expression; Genetic aspects; Genetics; Genomes; Microorganisms; Mitochondria; Mitochondria - enzymology; Mitochondrial DNA; Mutagenesis; Mutation; Nuclei; Peripheral neuropathy; Ribonucleotide reductase; Saccharomyces cerevisiae; Saccharomyces cerevisiae - enzymology; Saccharomyces cerevisiae - genetics; Saccharomyces cerevisiae Proteins - genetics; Saccharomyces cerevisiae Proteins - metabolism; Yeast
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0034322

In yeast, DNA polymerase zeta (Rev3 and Rev7) and Rev1, involved in the error-prone translesion synthesis during replication of nuclear DNA, localize also in mitochondria. We show that overexpression of Rev3 reduced the mtDNA extended mutability caused by a subclass of pathological mutations in Mip1, the yeast mitochondrial DNA polymerase orthologous to human Pol gamma. This beneficial effect was synergistic with the effect achieved by increasing the dNTPs pools. Since overexpression of Rev3 is detrimental for nuclear DNA mutability, we constructed a mutant Rev3 isoform unable to migrate into the nucleus: its overexpression reduced mtDNA mutability without increasing the nuclear one.