The influence of the DNA polymerase γ accessory subunit on base excision repair by the catalytic subunit

Mammalian DNA polymerase γ, the sole polymerase responsible for replication and repair of mitochondrial DNA, contains a large catalytic subunit and a smaller accessory subunit, pol γB. In addition to the polymerase domain, the large subunit contains a 3′–5′ editing exonuclease domain as well as a dRP lyase activity that can remove a 5′-deoxyribosephosphate (dRP) group during base excision repair. We show that the accessory subunit enhances the ability of the catalytic subunit to function in base excision repair mainly by stimulating two subreactions in the repair process. Pol γB appeared to specifically enhance the rate at which pol γ was able to locate damage in high molecular weight DNA. One pol γB point mutant known to have impaired ability to bind duplex DNA stimulated repair poorly, suggesting that duplex DNA binding through pol γB may help the catalytic subunit locate sites of DNA damage. In addition, the small subunit significantly stimulated the dRP lyase activity of pol γA, although it did not increase the rate at which the dRP group dissociated from the enzyme. The ability of DNA pol γ to process a high load of damaged DNA may be compromised by the slow release of the dRP group.