PrimPol Is Required for Replicative Tolerance of G Quadruplexes in Vertebrate Cells

Mol Cell. 2016 Jan 7;61(1):161-9. doi: 10.1016/j.molcel.2015.10.038. Epub 2015 Nov 25.


G quadruplexes (G4s) can present potent blocks to DNA replication. Accurate and timely replication of G4s in vertebrates requires multiple specialized DNA helicases and polymerases to prevent genetic and epigenetic instability. Here we report that PrimPol, a recently described primase-polymerase (PrimPol), plays a crucial role in the bypass of leading strand G4 structures. While PrimPol is unable to directly replicate G4s, it can bind and reprime downstream of these structures. Disruption of either the catalytic activity or zinc-finger of PrimPol results in extreme G4-dependent epigenetic instability at the BU-1 locus in avian DT40 cells, indicative of extensive uncoupling of the replicative helicase and polymerase. Together, these observations implicate PrimPol in promoting restart of DNA synthesis downstream of, but closely coupled to, G4 replication impediments.

Keywords: G quadruplexes; PrimPol; TLS; epigenetic instability; polymerase; primase; replication stalling; repriming.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Avian Proteins / genetics
  • Avian Proteins / metabolism*
  • Base Sequence
  • Cell Line
  • Chickens
  • Chromatin Assembly and Disassembly
  • DNA / biosynthesis*
  • DNA / chemistry
  • DNA Primase / genetics
  • DNA Primase / metabolism*
  • DNA Replication*
  • DNA-Directed DNA Polymerase / genetics
  • DNA-Directed DNA Polymerase / metabolism*
  • Epigenesis, Genetic
  • G-Quadruplexes*
  • Genomic Instability
  • Histones / metabolism
  • Molecular Sequence Data
  • Multifunctional Enzymes / genetics
  • Multifunctional Enzymes / metabolism*
  • Transfection


  • Avian Proteins
  • Histones
  • Multifunctional Enzymes
  • DNA
  • DNA Primase
  • PrimPol protein, human
  • DNA-Directed DNA Polymerase