Several pathological mutations have been identified in human POLG gene, encoding for the catalytic subunit of Pol γ, the solely mitochondrial replicase in animals and fungi. However, little is known regarding non-pathological polymorphisms found in this gene. Here we studied, in the yeast model Saccharomyces cerevisiae, eight human polymorphisms. We found that most of them are not neutral but enhanced both mtDNA extended mutability and the accumulation of mtDNA point mutations, either alone or in combination with a pathological mutation. In addition, we found that the presence of some SNPs increased the stavudine and/or zalcitabine-induced mtDNA mutability and instability.

Polymorphisms in DNA polymerase γ affect the mtDNA stability and the NRTI-induced mitochondrial toxicity in Saccharomyces cerevisiae / Baruffini, Enrico; Ferrari, Jessica; Dallabona, Cristina; Donnini, Claudia; Lodi, Tiziana. - In: MITOCHONDRION. - ISSN 1567-7249. - 20:(2015), pp. 52-63. [10.1016/j.mito.2014.11.003]

Polymorphisms in DNA polymerase γ affect the mtDNA stability and the NRTI-induced mitochondrial toxicity in Saccharomyces cerevisiae

BARUFFINI, Enrico
;
DALLABONA, Cristina
Investigation
;
DONNINI, Claudia
Supervision
;
LODI, Tiziana
2015-01-01

Abstract

Several pathological mutations have been identified in human POLG gene, encoding for the catalytic subunit of Pol γ, the solely mitochondrial replicase in animals and fungi. However, little is known regarding non-pathological polymorphisms found in this gene. Here we studied, in the yeast model Saccharomyces cerevisiae, eight human polymorphisms. We found that most of them are not neutral but enhanced both mtDNA extended mutability and the accumulation of mtDNA point mutations, either alone or in combination with a pathological mutation. In addition, we found that the presence of some SNPs increased the stavudine and/or zalcitabine-induced mtDNA mutability and instability.
Polymorphisms in DNA polymerase γ affect the mtDNA stability and the NRTI-induced mitochondrial toxicity in Saccharomyces cerevisiae / Baruffini, Enrico; Ferrari, Jessica; Dallabona, Cristina; Donnini, Claudia; Lodi, Tiziana. - In: MITOCHONDRION. - ISSN 1567-7249. - 20:(2015), pp. 52-63. [10.1016/j.mito.2014.11.003]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11381/2783071
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