The influence of the DNA polymerase gamma accessory subunit on base excision repair by the catalytic subunit.
Mammalian DNA polymerase gamma, the sole polymerase responsible for replication and repair of mitochondrial DNA, contains a large catalytic subunit and a smaller accessory subunit, pol gammaB. 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 gammaB appeared to specifically enhance the rate at which pol gamma was able to locate damage in high molecular weight DNA. One pol gammaB point mutant known to have impaired ability to bind duplex DNA stimulated repair poorly, suggesting that duplex DNA binding through pol gammaB may help the catalytic subunit locate sites of DNA damage. In addition, the small subunit significantly stimulated the dRP lyase activity of pol gammaA, although it did not increase the rate at which the dRP group dissociated from the enzyme. The ability of DNA pol gamma to process a high load of damaged DNA may be compromised by the slow release of the dRP group.
Pinz
Kevin G
KG
Department of Pharmacological Sciences, State University of New York at Stony Brook, Basic Health Science, Stony Brook, NY 11794-8651, USA.
Bogenhagen
Daniel F
DF
D000818:Animals; D020134:Catalytic Domain; D002478:Cells, Cultured; D000074002:DNA Polymerase gamma; D004260:DNA Repair / Q000502:physiology*; D004272:DNA, Mitochondrial / Q000235:genetics / Q000378:metabolism; D004259:DNA-Directed DNA Polymerase / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D016296:Mutagenesis; D009154:Mutation; D019761:Phosphorus-Oxygen Lyases / Q000378:metabolism; D021122:Protein Subunits; D012267:Ribosemonophosphates / Q000378:metabolism
C502791:5'-deoxyribose-5-phosphate; D004272:DNA, Mitochondrial; D021122:Protein Subunits; D012267:Ribosemonophosphates; C423906:5'-deoxyribose phosphate lyase; D000074002:DNA Polymerase gamma; D004259:DNA-Directed DNA Polymerase; D019761:Phosphorus-Oxygen Lyases