DNA polymerase eta is involved in hypermutation occurring during immunoglobulin class switch recombination

J Exp Med. 2004 Jan 19;199(2):265-70. doi: 10.1084/jem.20031831.


Base substitutions, deletions, and duplications are observed at the immunoglobulin locus in DNA sequences involved in class switch recombination (CSR). These mutations are dependent upon activation-induced cytidine deaminase (AID) and present all the characteristics of the ones observed during V gene somatic hypermutation, implying that they could be generated by the same mutational complex. It has been proposed, based on the V gene mutation pattern of patients with the cancer-prone xeroderma pigmentosum variant (XP-V) syndrome who are deficient in DNA polymerase eta (pol eta), that this enzyme could be responsible for a large part of the mutations occurring on A/T bases. Here we show, by analyzing switched memory B cells from two XP-V patients, that pol eta is also an A/T mutator during CSR, in both the switch region of tandem repeats as well as upstream of it, thus suggesting that the same error-prone translesional polymerases are involved, together with AID, in both processes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • B-Lymphocytes / immunology
  • Base Sequence
  • Cytidine Deaminase
  • Cytosine Deaminase / metabolism
  • DNA / genetics
  • DNA Mutational Analysis
  • DNA Primers / genetics
  • DNA-Directed DNA Polymerase / deficiency
  • DNA-Directed DNA Polymerase / genetics
  • DNA-Directed DNA Polymerase / metabolism*
  • Female
  • Humans
  • Immunoglobulin Class Switching*
  • Immunologic Memory
  • Introns
  • Middle Aged
  • Molecular Sequence Data
  • Recombination, Genetic
  • Somatic Hypermutation, Immunoglobulin*
  • Xeroderma Pigmentosum / enzymology
  • Xeroderma Pigmentosum / genetics
  • Xeroderma Pigmentosum / immunology


  • DNA Primers
  • DNA
  • DNA-Directed DNA Polymerase
  • Rad30 protein
  • AICDA (activation-induced cytidine deaminase)
  • Cytosine Deaminase
  • Cytidine Deaminase