Cellular and Molecular Life Sciences

, Volume 68, Issue 2, pp 219–233

Mitochondrial DNA replication and disease: insights from DNA polymerase γ mutations

Review

DOI: 10.1007/s00018-010-0530-4

Cite this article as:
Stumpf, J.D. & Copeland, W.C. Cell. Mol. Life Sci. (2011) 68: 219. doi:10.1007/s00018-010-0530-4

Abstract

DNA polymerase γ (pol γ), encoded by POLG, is responsible for replicating human mitochondrial DNA. About 150 mutations in the human POLG have been identified in patients with mitochondrial diseases such as Alpers syndrome, progressive external ophthalmoplegia, and ataxia-neuropathy syndromes. Because many of the mutations are described in single citations with no genotypic family history, it is important to ascertain which mutations cause or contribute to mitochondrial disease. The vast majority of data about POLG mutations has been generated from biochemical characterizations of recombinant pol γ. However, recently, the study of mitochondrial dysfunction in Saccharomyces cerevisiae and mouse models provides important in vivo evidence for the role of POLG mutations in disease. Also, the published 3D-structure of the human pol γ assists in explaining some of the biochemical and genetic properties of the mutants. This review summarizes the current evidence that identifies and explains disease-causing POLG mutations.

Keywords

MitochondriamtDNA replicationDNA polymerase gammaPOLGDNA repair

Copyright information

© Springer Basel AG (outside the USA) 2010

Authors and Affiliations

  1. 1.Laboratory of Molecular GeneticsNational Institute of Environmental Health Sciences, National Institutes of HealthResearch Triangle ParkUSA