Reevaluation of the role of DNA polymerase θ in somatic hypermutation of immunoglobulin genes

Stella A. Martomo, Huseyin Saribasak, Masayuki Yokoi, Fumio Hanaoka, Patricia J. Gearhart

Research output: Contribution to journalArticle

Abstract

DNA polymerase θ has been implicated in the process of somatic hypermutation in immunoglobulin variable genes based on several reports of alterations in the frequency and spectra of mutations from Polq-/- mice. However, these studies have contrasting results on mutation frequencies and the types of nucleotide substitutions, which question the role of polymerase θ in hypermutation. DNA polymerase η has a dominant effect on mutation and may substitute in the absence of polymerase θ to affect the pattern. Therefore, we have examined mutation in mice deficient for both polymerases θ and η. The mutation frequencies in rearranged variable genes from Peyer's patches were similar in wild type, Polq-/-, Polh-/-, and Polq-/-Polh-/- mice. The types of substitutions were also similar between wild type and Polq-/- clones, and between Polh-/- and Polq-/-Polh-/- clones. Furthermore, there was no difference in heavy chain class switching in splenic B cells from the four groups of mice. These results indicate that polymerase θ does not play a significant role in the generation of somatic mutation in immunoglobulin genes.

Original languageEnglish (US)
Pages (from-to)1603-1608
Number of pages6
JournalDNA Repair
Volume7
Issue number9
DOIs
StatePublished - Sep 1 2008

Keywords

  • Class switch recombination
  • DNA polymerase η
  • DNA polymerase θ
  • Immunoglobulin gene
  • Somatic hypermutation

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Martomo, S. A., Saribasak, H., Yokoi, M., Hanaoka, F., & Gearhart, P. J. (2008). Reevaluation of the role of DNA polymerase θ in somatic hypermutation of immunoglobulin genes. DNA Repair, 7(9), 1603-1608. https://doi.org/10.1016/j.dnarep.2008.04.002