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

被引：20

作者：

Baruffini, Enrico ^{[1
]}

Horvath, Rita ^{[2
,3
]}

Dallabona, Cristina ^{[1
]}

Czermin, Birgit ^{[3
]}

Lamantea, Eleonora ^{[4
]}

Bindoff, Laurence ^{[5
]}

Invernizzi, Federica ^{[4
]}

Ferrero, Iliana ^{[1
]}

Zeviani, Massimo ^{[4
]}

Lodi, Tiziana ^{[1
]}

机构：

[1] Univ Parma, Dept Genet, I-43124 Parma, Italy

[2] Newcastle Univ, Mitochondrial Res Grp, Inst Hlth & Aging, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England

[3] Ctr Med Genet, Munich, Germany

[4] Pierfranco & Luisa Mariani Ctr Study Childrens Mi, Unit Mol Neurogenet, Milan, Italy

[5] Haukeland Hosp, Dept Neurol, N-5021 Bergen, Norway

来源：

MITOCHONDRION | 2011年 / 11卷 / 01期

关键词：

Yeast model; POLG; Mitochondrial diseases; MIPI; mtDNA mutability; ROS scavengers; DNA-POLYMERASE-GAMMA; PROGRESSIVE EXTERNAL OPHTHALMOPLEGIA; MITOCHONDRIAL-DNA; SACCHAROMYCES-CEREVISIAE; RIB2; LOCUS; DEFECTS; GENE; REPLICATION; MTDNA; ERYTHROMYCIN;

D O I：

10.1016/j.mito.2010.09.007

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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 C303R, 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. (C) 2010 Elsevier B.V. and Mitochondria Research Society. All rights reserved.

引用

页码：182 / 190

页数：9

共 36 条

[11] Structure-function defects of human mitochondrial DNA polymerase in autosomal dominant progressive external ophthalmoplegia [J].