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Papers In Press, published online ahead of print November 1, 2005
Pharmacological Sciences, SUNY Stony Brook, Stony Brook, NY 11794-8651
Corresponding Author: dan{at}pharm.sunysb.edu
Mitochondrial DNA polymerase
J. Biol. Chem, 10.1074/jbc.M509730200
Submitted on September 2, 2005
Revised on October 28, 2005
Accepted on October 31, 2005
Functional human mitochondrial DNA polymerase
forms a heterotrimer
(pol
) is responsible for replication and repair of mtDNA and is mutated in individuals with genetic disorders such as chronic external opthalmoplegia and Alpers syndrome. Pol
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
catalytic subunit with both the wild-type accessory factor, pol
B, and a deletion derivative that is unable to dimerize and consequently is impaired in its ability to stimulate processive DNA synthesis. Our studies clearly show that the functional human holoenzyme contains two subunits of the processivity factor and one catalytic subunit, thereby forming a heterotrimer. The structure of pol
. seems to be variable, ranging from a single catalytic subunit in yeast to a heterodimer in Drosophila and a heterotrimer in mammals.
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