PrimPol is required for replication reinitiation after mtDNA damage

Proc Natl Acad Sci U S A. 2017 Oct 24;114(43):11398-11403. doi: 10.1073/pnas.1705367114. Epub 2017 Oct 9.

Abstract

Eukaryotic PrimPol is a recently discovered DNA-dependent DNA primase and translesion synthesis DNA polymerase found in the nucleus and mitochondria. Although PrimPol has been shown to be required for repriming of stalled replication forks in the nucleus, its role in mitochondria has remained unresolved. Here we demonstrate in vivo and in vitro that PrimPol can reinitiate stalled mtDNA replication and can prime mtDNA replication from nonconventional origins. Our results not only help in the understanding of how mitochondria cope with replicative stress but can also explain some controversial features of the lagging-strand replication.

Keywords: DNA repair; fork rescue; mtDNA damage; mtDNA replication.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Cells, Cultured
  • Culture Media
  • DNA Replication / physiology*
  • DNA, Mitochondrial / metabolism*
  • DNA-Directed DNA Polymerase / genetics
  • DNA-Directed DNA Polymerase / metabolism*
  • Fibroblasts
  • Gene Deletion
  • Mice
  • Pyridines
  • Ultraviolet Rays

Substances

  • 3,5-diethoxycarbonyl-1,4-dihydrocollidine
  • Culture Media
  • DNA, Mitochondrial
  • Pyridines
  • DNA-Directed DNA Polymerase
  • Primpol protein, mouse