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Normal hypermutation in antibody genes from congenic mice defective for DNA polymerase ι

DNA Repair
Publication Date
DOI: 10.1016/j.dnarep.2005.12.006
  • Immunoglobulins
  • Somatic Hypermutation
  • Class Switch Recombination
  • Pol ι
  • Pol η
  • Congenic Mice
  • Biology


Abstract Several low fidelity DNA polymerases participate in generating mutations in immunoglobulin genes. Polymerase η is clearly involved in the process by causing substitutions of A:T base pairs, whereas polymerase ι has a controversial role. Although the frequency of mutations was decreased in the BL2 cell line deficient for polymerase ι, hypermutation was normal in the 129 strain of mice, which has a natural nonsense mutation in the Poli gene. It is possible that the mice compensated for the defect over time, or that polymerase η substituted in the absence of polymerase ι. To examine polymerase ι in a genetically defined background, we backcrossed the 129 nonsense mutation to the C57BL/6 strain for six generations. Class switch recombination and hypermutation were studied in these mice and in congenic mice doubly deficient for both polymerases ι and η. The absence of both polymerases did not affect production of IgG1, indicating that these enzymes are not involved in switch recombination. Poli −/− F6 mice had the same types of nucleotide substitutions in variable genes as their C57BL/6 counterparts, and mice doubly deficient for polymerases ι and η had the same mutational spectrum as Polh −/− mice. Thus, polymerase ι did not contribute to the mutational spectra, even in the absence of polymerase η.

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