Reevaluation of the role of DNA polymerase theta in somatic hypermutation of immunoglobulin genes.
DNA polymerase theta 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 theta in hypermutation. DNA polymerase eta has a dominant effect on mutation and may substitute in the absence of polymerase theta to affect the pattern. Therefore, we have examined mutation in mice deficient for both polymerases theta and eta. 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 theta does not play a significant role in the generation of somatic mutation in immunoglobulin genes.
Martomo
Stella A
SA
Laboratory of Molecular Gerontology, National Institute on Aging, National Institutes of Health, 5600 Nathan Shock Drive, Baltimore, MD 21224, USA.
Saribasak
Huseyin
H
Yokoi
Masayuki
M
Hanaoka
Fumio
F
Gearhart
Patricia J
PJ
D000818:Animals; D004259:DNA-Directed DNA Polymerase / Q000502:physiology*; D005803:Genes, Immunoglobulin; D017578:Immunoglobulin Class Switching; D051379:Mice; D008810:Mice, Inbred C57BL; D010581:Peyer's Patches; D027041:Somatic Hypermutation, Immunoglobulin; D013154:Spleen; D000097462:DNA Polymerase theta; D000099270:Y-Family DNA Polymerases
D004259:DNA-Directed DNA Polymerase; D000097462:DNA Polymerase theta; C112338:Rad30 protein; D000099270:Y-Family DNA Polymerases