title: Functional human mitochondrial DNA polymerase gamma forms a heterotrimer.
abstract: Mitochondrial DNA polymerase gamma (pol gamma) is responsible for replication and repair of mtDNA and is mutated in individuals with genetic disorders such as chronic external ophthalmoplegia and Alpers syndrome. pol gamma is also an adventitious target for toxic side effects of several antiviral compounds, and mutation of its proofreading exonuclease leads to accelerated aging in mouse models. We have used a variety of physical and functional approaches to study the interaction of the human pol gamma catalytic subunit with both the wild-type accessory factor, pol gammaB, and a deletion derivative that is unable to dimerize and consequently is impaired in its ability to stimulate processive DNA synthesis. Our studies clearly showed that the functional human holoenzyme contains two subunits of the processivity factor and one catalytic subunit, thereby forming a heterotrimer. The structure of pol gamma seems to be variable, ranging from a single catalytic subunit in yeast to a heterodimer in Drosophila and a heterotrimer in mammals.
authors.affiliation: Department of Pharmacological Sciences and Center for Structural Biology, State University of New York, Stony Brook, New York 11794-8651, USA.
authors.forename: Elena
authors.initials: E
authors.lastname: Yakubovskaya
authors.forename: Zhixin
authors.initials: Z
authors.lastname: Chen
authors.forename: José A
authors.initials: JA
authors.lastname: Carrodeguas
authors.forename: Caroline
authors.initials: C
authors.lastname: Kisker
authors.forename: Daniel F
authors.initials: DF
authors.lastname: Bogenhagen
mesh_terms: D000074002:DNA Polymerase gamma; D004260:DNA Repair; D004261:DNA Replication; D004272:DNA, Mitochondrial / Q000235:genetics; D004259:DNA-Directed DNA Polymerase / Q000737:chemistry* / Q000235:genetics*; D006801:Humans; D008928:Mitochondria / Q000235:genetics*; D009154:Mutation; D021122:Protein Subunits / Q000737:chemistry; D020349:Surface Plasmon Resonance
chemical_list: D004272:DNA, Mitochondrial; D021122:Protein Subunits; D000074002:DNA Polymerase gamma; D004259:DNA-Directed DNA Polymerase