Exonuclease of human DNA polymerase gamma disengages its strand displacement function

Mitochondrion. 2013 Nov;13(6):592-601. doi: 10.1016/j.mito.2013.08.003. Epub 2013 Aug 30.

Abstract

Pol γ, the only DNA polymerase found in human mitochondria, functions in both mtDNA repair and replication. During mtDNA base-excision repair, gaps are created after damaged base excision. Here we show that Pol γ efficiently gap-fills except when the gap is only a single nucleotide. Although wild-type Pol γ has very limited ability for strand displacement DNA synthesis, exo(-) (3'-5' exonuclease-deficient) Pol γ has significantly high activity and rapidly unwinds downstream DNA, synthesizing DNA at a rate comparable to that of the wild-type enzyme on a primer-template. The catalytic subunit Pol γA alone, even when exo(-), is unable to synthesize by strand displacement, making this the only known reaction of Pol γ holoenzyme that has an absolute requirement for the accessory subunit Pol γB.

Keywords: DNA repair and replication; Molecular motor; Strand displacement.

MeSH terms

  • Base Sequence
  • DNA Polymerase gamma
  • DNA Repair
  • DNA, Mitochondrial / chemistry
  • DNA, Mitochondrial / metabolism*
  • DNA-Directed DNA Polymerase / metabolism*
  • Electrophoretic Mobility Shift Assay
  • Exonucleases / metabolism*
  • Humans

Substances

  • DNA, Mitochondrial
  • DNA Polymerase gamma
  • DNA-Directed DNA Polymerase
  • Exonucleases