Book of Abstracts: Albany 2007
June 19-23 2007
Primer-Template Recognition by the Mitochondrial DNA Polymerase Gamma
Mitochondrial DNA polymerase Gamma (Pol G) is the single polymerase responsible for replication and repair of mitochondrial DNA. Mutations in this enzyme are linked to genetic disorders such as chronic external ophthalmoplegia and lead to accelerated aging in mouse models. Previous studies have shown that the functional human Pol G contains a 139kD catalytic subunit and a 53kD processivity factor which is a dimer . This accessory factor differs from the conventional sliding-clamps such as human PCNA and E. coli DNA pol III β proteins as it evolved from a bacterial tRNA synthetase. In the past, several models have been proposed for the path of DNA through Pol G holoenzyme, but none have been confirmed. We employed molecular techniques such as enzyme kinetics, footprinting, and photo-crosslinking to characterize the binding pocket of Pol G and to establish a model for the DNA path through the holoenzyme. In addition, we attempted to understand the functional involvement of each of the Pol G subunits in DNA binding.
References and Footnotes
Dept of Pharmacological Sciences,