TY - JOUR
T1 - Predicting the contribution of novel POLG mutations to human disease through analysis in yeast model
AU - Baruffini, Enrico
AU - Horvath, Rita
AU - Dallabona, Cristina
AU - Czermin, Birgit
AU - Lamantea, Eleonora
AU - Bindoff, Laurence
AU - Invernizzi, Federica
AU - Ferrero, Iliana
AU - Zeviani, Massimo
AU - Lodi, Tiziana
PY - 2011/1
Y1 - 2011/1
N2 - 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.
AB - 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.
KW - MIP1
KW - Mitochondrial diseases
KW - MtDNA mutability
KW - POLG
KW - ROS scavengers
KW - Yeast model
UR - http://www.scopus.com/inward/record.url?scp=78649984326&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=78649984326&partnerID=8YFLogxK
U2 - 10.1016/j.mito.2010.09.007
DO - 10.1016/j.mito.2010.09.007
M3 - Article
C2 - 20883824
AN - SCOPUS:78649984326
VL - 11
SP - 182
EP - 190
JO - Mitochondrion
JF - Mitochondrion
SN - 1567-7249
IS - 1
ER -