PrimPol bypasses UV photoproducts during eukaryotic chromosomal DNA replication

Mol Cell. 2013 Nov 21;52(4):566-73. doi: 10.1016/j.molcel.2013.10.035.


DNA damage can stall the DNA replication machinery, leading to genomic instability. Thus, numerous mechanisms exist to complete genome duplication in the absence of a pristine DNA template, but identification of the enzymes involved remains incomplete. Here, we establish that Primase-Polymerase (PrimPol; CCDC111), an archaeal-eukaryotic primase (AEP) in eukaryotic cells, is involved in chromosomal DNA replication. PrimPol is required for replication fork progression on ultraviolet (UV) light-damaged DNA templates, possibly mediated by its ability to catalyze translesion synthesis (TLS) of these lesions. This PrimPol UV lesion bypass pathway is not epistatic with the Pol η-dependent pathway and, as a consequence, protects xeroderma pigmentosum variant (XP-V) patient cells from UV-induced cytotoxicity. In addition, we establish that PrimPol is also required for efficient replication fork progression during an unperturbed S phase. These and other findings indicate that PrimPol is an important player in replication fork progression in eukaryotic cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Cell Proliferation
  • Cell Survival
  • Chickens
  • Chromosomes, Human / genetics*
  • DNA Adducts / chemistry
  • DNA Adducts / genetics*
  • DNA Adducts / metabolism
  • DNA Damage
  • DNA Primase / chemistry
  • DNA Primase / physiology*
  • DNA Replication*
  • DNA, Single-Stranded / chemistry
  • DNA-Directed DNA Polymerase / chemistry
  • DNA-Directed DNA Polymerase / physiology*
  • G2 Phase Cell Cycle Checkpoints
  • Gene Knockdown Techniques
  • HEK293 Cells
  • Humans
  • Mice
  • Mice, Knockout
  • Molecular Sequence Data
  • Multifunctional Enzymes / chemistry
  • Multifunctional Enzymes / physiology*
  • Ultraviolet Rays
  • Xenopus


  • DNA Adducts
  • DNA, Single-Stranded
  • Multifunctional Enzymes
  • DNA Primase
  • PrimPol protein, human
  • DNA-Directed DNA Polymerase