PrimPol prevents APOBEC/AID family mediated DNA mutagenesis

Nucleic Acids Res. 2016 Jun 2;44(10):4734-44. doi: 10.1093/nar/gkw123. Epub 2016 Feb 28.


PrimPol is a DNA damage tolerant polymerase displaying both translesion synthesis (TLS) and (re)-priming properties. This led us to study the consequences of a PrimPol deficiency in tolerating mutagenic lesions induced by members of the APOBEC/AID family of cytosine deaminases. Interestingly, during somatic hypermutation, PrimPol counteracts the generation of C>G transversions on the leading strand. Independently, mutation analyses in human invasive breast cancer confirmed a pro-mutagenic activity of APOBEC3B and revealed a genome-wide anti-mutagenic activity of PRIMPOL as well as most Y-family TLS polymerases. PRIMPOL especially prevents APOBEC3B targeted cytosine mutations within TpC dinucleotides. As C transversions induced by APOBEC/AID family members depend on the formation of AP-sites, we propose that PrimPol reprimes preferentially downstream of AP-sites on the leading strand, to prohibit error-prone TLS and simultaneously stimulate error-free homology directed repair. These in vivo studies are the first demonstrating a critical anti-mutagenic activity of PrimPol in genome maintenance.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • B-Lymphocytes / enzymology
  • Breast Neoplasms / enzymology
  • Breast Neoplasms / genetics
  • CRISPR-Cas Systems
  • Cell Line
  • Cell Survival / radiation effects
  • Cells, Cultured
  • Cytidine Deaminase / antagonists & inhibitors
  • Cytidine Deaminase / metabolism*
  • DNA / metabolism
  • DNA Primase / physiology*
  • DNA Replication
  • DNA-Directed DNA Polymerase / physiology*
  • Female
  • Humans
  • Immunoglobulin Class Switching
  • Mice, Inbred C57BL
  • Minor Histocompatibility Antigens / metabolism*
  • Multifunctional Enzymes / physiology*
  • Mutagenesis*
  • Somatic Hypermutation, Immunoglobulin
  • T-Lymphocytes / enzymology
  • Ultraviolet Rays


  • Minor Histocompatibility Antigens
  • Multifunctional Enzymes
  • DNA
  • DNA Primase
  • PrimPol protein, human
  • DNA-Directed DNA Polymerase
  • APOBEC3B protein, human
  • Cytidine Deaminase