DNA polymerase gamma in mitochondrial DNA replication and repair.


Mutations in mitochondrial DNA (mtDNA) are associated with aging, and ...
Mutations in mitochondrial DNA (mtDNA) are associated with aging, and they can cause tissue degeneration and neuromuscular pathologies known as mitochondrial diseases. Because DNA polymerase gamma (pol gamma) is the enzyme responsible for replication and repair of mitochondrial DNA, the burden of faithful duplication of mitochondrial DNA, both in preventing spontaneous errors and in DNA repair synthesis, falls on pol gamma. Investigating the biological functions of pol gamma and its inhibitors aids our understanding of the sources of mtDNA mutations. In animal cells, pol gamma is composed of two subunits, a larger catalytic subunit of 125-140 kDa and second subunit of 35-55 kDa. The catalytic subunit contains DNA polymerase activity, 3'-5' exonuclease activity, and a 5'-dRP lyase activity. The accessory subunit is required for highly processive DNA synthesis and increases the affinity of pol gamma to the DNA.




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