Mutations in human DNA polymerase γ confer unique mechanisms of catalytic deficiency that mirror the disease severity in mitochondrial disorder patients.

ABSTRACT: Human mitochondrial DNA polymerase γ (pol γ) is solely responsible for the replication and repair of the mitochondrial genome. Unsurprisingly, alterations in pol γ activity have been associated with mitochondrial diseases such as Alpers syndrome and progressive external ophthalmoplegia. Thus far, predicting the severity of mitochondrial disease based the magnitude of deficiency in pol γ activity has been difficult. In order to understand the relationship between disease severity in patients and enzymatic defects in vitro, we characterized the molecular mechanisms of four pol γ mutations, A957P, A957S, R1096C and R1096H, which have been found in patients suffering from aggressive Alpers syndrome to mild progressive external ophthalmoplegia. The A957P mutant showed the most striking deficien

SUBMITTER: Sohl CD 

PROVIDER: S-EPMC3578408 | biostudies-literature | 2013 Mar

REPOSITORIES: biostudies-literature