The mitochondrial DNA polymerase gamma degrades linear DNA fragments precluding the formation of deletions

Nat Commun. 2018 Jun 27;9(1):2491. doi: 10.1038/s41467-018-04895-1.

Abstract

Double-strand breaks in the mitochondrial DNA (mtDNA) result in the formation of linear fragments that are rapidly degraded. However, the identity of the nuclease(s) performing this function is not known. We found that the exonuclease function of the mtDNA polymerase gamma (POLG) is required for this rapid degradation of mtDNA fragments. POLG is recruited to linearized DNA fragments in an origin of replication-independent manner. Moreover, in the absence of POLG exonuclease activity, the prolonged existence of mtDNA linear fragments leads to increased levels of mtDNA deletions, which have been previously identified in the mutator mouse, patients with POLG mutations and normal aging.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence / genetics
  • Cells, Cultured
  • DNA Breaks, Double-Stranded
  • DNA Polymerase gamma / metabolism*
  • DNA, Mitochondrial / genetics
  • DNA, Mitochondrial / metabolism*
  • Fibroblasts
  • Mice
  • Mice, Transgenic
  • Mitochondria / metabolism*
  • Mutation
  • Primary Cell Culture
  • Sequence Deletion*

Substances

  • DNA, Mitochondrial
  • DNA Polymerase gamma
  • Polg protein, mouse