Error rate and specificity of human and murine DNA polymerase eta

J Mol Biol. 2001 Sep 14;312(2):335-46. doi: 10.1006/jmbi.2001.4937.


We describe here the error specificity of mammalian DNA polymerase eta (pol eta), an enzyme that performs translesion DNA synthesis and may participate in somatic hypermutation of immunoglobulin genes. Both mouse and human pol eta lack intrinsic proofreading exonuclease activity and both copy undamaged DNA inaccurately. Analysis of more than 1500 single-base substitutions by human pol eta indicates that error rates for all 12 mismatches are high and variable depending on the composition and symmetry of the mismatch and its location. pol eta also generates tandem base substitutions at an unprecedented rate, and kinetic analysis indicates that it extends a tandem double mismatch about as efficiently as other replicative enzymes extend single-base mismatches. This ability to use an aberrant primer terminus and the high rate of single and double-base substitutions support the idea that pol eta may forego strict shape complementarity in order to facilitate highly efficient lesion bypass. Relaxed discrimination is further indicated by pol eta infidelity for a wide variety of nucleotide deletion and addition errors. The nature and location of these errors suggest that some may be initiated by strand slippage, while others result from additional mechanisms.

MeSH terms

  • Animals
  • Base Pair Mismatch / genetics
  • Base Sequence
  • DNA Damage / genetics
  • DNA Mutational Analysis
  • DNA Replication*
  • DNA-Directed DNA Polymerase / chemistry
  • DNA-Directed DNA Polymerase / metabolism*
  • Frameshift Mutation / genetics
  • Genes, Immunoglobulin / genetics
  • Humans
  • Kinetics
  • Lac Operon / genetics
  • Mice
  • Molecular Sequence Data
  • Mutagenesis* / genetics
  • Point Mutation / genetics
  • Sequence Deletion / genetics
  • Substrate Specificity
  • Templates, Genetic


  • DNA-Directed DNA Polymerase
  • Rad30 protein