Contribution of DNA polymerase eta to immunoglobulin gene hypermutation in the mouse

J Exp Med. 2005 Apr 18;201(8):1191-6. doi: 10.1084/jem.20050292. Epub 2005 Apr 11.

Abstract

The mutation pattern of immunoglobulin genes was studied in mice deficient for DNA polymerase eta, a translesional polymerase whose inactivation is responsible for the xeroderma pigmentosum variant (XP-V) syndrome in humans. Mutations show an 85% G/C biased pattern, similar to that reported for XP-V patients. Breeding these mice with animals harboring the stop codon mutation of the 129/Olain background in their DNA polymerase iota gene did not alter this pattern further. Although this G/C biased mutation profile resembles that of mice deficient in the MSH2 or MSH6 components of the mismatch repair complex, the residual A/T mutagenesis of pol eta-deficient mice differs markedly. This suggests that, in the absence of pol eta, the MSH2-MSH6 complex is able to recruit another DNA polymerase that is more accurate at copying A/T bases, possibly pol kappa, to assume its function in hypermutation.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • B-Lymphocytes
  • Base Pair Mismatch
  • Base Sequence
  • DNA Repair
  • DNA-Directed DNA Polymerase / deficiency*
  • DNA-Directed DNA Polymerase / genetics
  • Genes, Immunoglobulin*
  • Mice
  • Mice, Knockout
  • Molecular Sequence Data
  • Peyer's Patches
  • Somatic Hypermutation, Immunoglobulin*

Substances

  • DNA polymerase iota
  • DNA-Directed DNA Polymerase
  • Rad30 protein