Predicting the contribution of novel POLG mutations to human disease through analysis in yeast model.

TitlePredicting the contribution of novel POLG mutations to human disease through analysis in yeast model.
Publication TypeJournal Article
Year of Publication2011
AuthorsBaruffini, E, Horvath, R, Dallabona, C, Czermin, B, Lamantea, E, Bindoff, L, Invernizzi, F, Ferrero, I, Zeviani, M, Lodi, T
Date Published2011 Jan
KeywordsAmino Acid Sequence, Antioxidants, DNA Polymerase gamma, DNA Polymerase I, DNA-Directed DNA Polymerase, Humans, Mitochondria, Mitochondrial Diseases, Molecular Sequence Data, Phenotype, Point Mutation, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Sequence Alignment

The yeast Saccharomyces cerevisiae was used to validate the pathogenic significance of eight human mutations in the gene encoding for the mitochondrial DNA polymerase gamma, namely G303R, S305R, R386H, R574W, P625R, D930N, K947R and P1073L, among which three are novel and four are of unclear pathological significance. Mitochondrial DNA extended and point mutability as well as dominance/recessivity of each mutation has been evaluated. The analysis in yeast revealed that two mutations, S305R and R386H, cannot be the sole cause of pathology observed in patients. These data led us to search for a second mutation in compound with S305R and we found a mutation, P1073L, missed in the first genetic analysis. Finally, a significant rescue of extended mutability has been observed for several dominant mutations by treatment with mitochondrial antioxidants.

Alternate JournalMitochondrion
Citation Key10.1016/j.mito.2010.09.007
PubMed ID20883824
Grant ListGGP07019 / / Telethon / Italy