DNA polymerase eta is an A-T mutator in somatic hypermutation of immunoglobulin variable genes

Nat Immunol. 2001 Jun;2(6):537-41. doi: 10.1038/88740.


To determine whether DNA polymerase eta plays a role in the hypermutation of immunoglobulin variable genes, we examined the frequency and pattern of substitutions in variable VH6 genes from the peripheral blood lymphocytes of three patients with xeroderma pigmentosum variant disease, whose polymerase eta had genetic defects. The frequency of mutation was normal but the types of base changes were different: there was a decrease in mutations at A and T and a concomitant rise in mutations at G and C. We propose that more than one polymerase contributes to hypermutation and that if one is absent, others compensate. The data indicate that polymerase eta is involved in generating errors that occur predominantly at A and T and that another polymerase(s) may preferentially generate errors opposite G and C.

MeSH terms

  • Animals
  • B-Lymphocytes / enzymology
  • B-Lymphocytes / immunology
  • Base Pairing
  • Base Sequence
  • DNA / genetics
  • DNA-Directed DNA Polymerase / genetics
  • DNA-Directed DNA Polymerase / metabolism*
  • Genes, Immunoglobulin*
  • Humans
  • Immunoglobulin Variable Region / genetics
  • Mice
  • Molecular Sequence Data
  • Mutation*
  • Xeroderma Pigmentosum / enzymology
  • Xeroderma Pigmentosum / genetics
  • Xeroderma Pigmentosum / immunology


  • Immunoglobulin Variable Region
  • DNA
  • DNA-Directed DNA Polymerase
  • Rad30 protein