Low fidelity DNA synthesis by human DNA polymerase-eta

Nature. 2000 Apr 27;404(6781):1011-3. doi: 10.1038/35010014.


A superfamily of DNA polymerases that bypass lesions in DNA has been described. Some family members are described as error-prone because mutations that inactivate the polymerase reduce damage-induced mutagenesis. In contrast, mutations in the skin cancer susceptibility gene XPV, which encodes DNA polymerase (pol)-eta, lead to increased ultraviolet-induced mutagenesis. This, and the fact that pol-eta primarily inserts adenines during efficient bypass of thymine-thymine dimers in vitro, has led to the description of pol-eta as error-free. However, here we show that human pol-eta copies undamaged DNA with much lower fidelity than any other template-dependent DNA polymerase studied. Pol-eta lacks an intrinsic proofreading exonuclease activity and, depending on the mismatch, makes one base substitution error for every 18 to 380 nucleotides synthesized. This very low fidelity indicates a relaxed requirement for correct base pairing geometry and indicates that the function of pol-eta may be tightly controlled to prevent potentially mutagenic DNA synthesis.

MeSH terms

  • DNA / biosynthesis*
  • DNA Damage
  • DNA Polymerase iota
  • DNA Repair
  • DNA-Directed DNA Polymerase / genetics
  • DNA-Directed DNA Polymerase / metabolism*
  • Humans
  • Mutagenesis


  • DNA
  • DNA-Directed DNA Polymerase
  • Rad30 protein
  • DNA Polymerase iota
  • POLI protein, human