TY - JOUR
T1 - Reevaluation of the role of DNA polymerase θ in somatic hypermutation of immunoglobulin genes
AU - Martomo, Stella A.
AU - Saribasak, Huseyin
AU - Yokoi, Masayuki
AU - Hanaoka, Fumio
AU - Gearhart, Patricia J.
N1 - Funding Information:
We thank J. Chrest, C. Morris, and R. Wersto for flow cytometry; the entire staff of the Comparative Medicine Section for mouse breeding; William Yang for technical help, and Robert Maul for comments. Mice heterozygous for pol θ were graciously provided by John Schimenti. This research was supported by the Intramural Research Program of the NIH, National Institute on Aging.
PY - 2008/9/1
Y1 - 2008/9/1
N2 - 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.
AB - 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.
KW - Class switch recombination
KW - DNA polymerase η
KW - DNA polymerase θ
KW - Immunoglobulin gene
KW - Somatic hypermutation
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U2 - 10.1016/j.dnarep.2008.04.002
DO - 10.1016/j.dnarep.2008.04.002
M3 - Article
C2 - 18485835
AN - SCOPUS:48149091758
SN - 1568-7864
VL - 7
SP - 1603
EP - 1608
JO - DNA Repair
JF - DNA Repair
IS - 9
ER -