DNA polymerases nu and theta are required for efficient immunoglobulin V gene diversification in chicken

J Cell Biol. 2010 Jun 28;189(7):1117-27. doi: 10.1083/jcb.200912012.

Abstract

The chicken DT40 B lymphocyte line diversifies its immunoglobulin (Ig) V genes through translesion DNA synthesis-dependent point mutations (Ig hypermutation) and homologous recombination (HR)-dependent Ig gene conversion. The error-prone biochemical characteristic of the A family DNA polymerases Polnu and Pol led us to explore the role of these polymerases in Ig gene diversification in DT40 cells. Disruption of both polymerases causes a significant decrease in Ig gene conversion events, although POLN(-/-)/POLQ(-/-) cells exhibit no prominent defect in HR-mediated DNA repair, as indicated by no increase in sensitivity to camptothecin. Poleta has also been previously implicated in Ig gene conversion. We show that a POLH(-/-)/POLN(-/-)/POLQ(-/-) triple mutant displays no Ig gene conversion and reduced Ig hypermutation. Together, these data define a role for Polnu and Pol in recombination and suggest that the DNA synthesis associated with Ig gene conversion is accounted for by three specialized DNA polymerases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Chickens
  • DNA Polymerase theta
  • DNA Repair
  • DNA-Directed DNA Polymerase / genetics*
  • Gene Conversion
  • Genetic Variation*
  • Immunoglobulin Variable Region / genetics*
  • Lymphocytes
  • Point Mutation
  • Recombination, Genetic
  • Somatic Hypermutation, Immunoglobulin

Substances

  • Immunoglobulin Variable Region
  • DNA-Directed DNA Polymerase