Contribution of DNA polymerase eta to immunoglobulin gene hypermutation in the mouse.
The mutation pattern of immunoglobulin genes was studied in mice deficient for DNA polymerase eta, a translesional polymerase whose inactivation is responsible for the xeroderma pigmentosum variant (XP-V) syndrome in humans. Mutations show an 85% G/C biased pattern, similar to that reported for XP-V patients. Breeding these mice with animals harboring the stop codon mutation of the 129/Olain background in their DNA polymerase iota gene did not alter this pattern further. Although this G/C biased mutation profile resembles that of mice deficient in the MSH2 or MSH6 components of the mismatch repair complex, the residual A/T mutagenesis of pol eta-deficient mice differs markedly. This suggests that, in the absence of pol eta, the MSH2-MSH6 complex is able to recruit another DNA polymerase that is more accurate at copying A/T bases, possibly pol kappa, to assume its function in hypermutation.
Delbos
Frédéric
F
Institut National de la Santé et de la Recherche Medicale U373, Faculté de Médecine Necker-Enfants Malades-Université Paris V, 75730 Paris Cedex 15, France.
De Smet
Annie
A
Faili
Ahmad
A
Aoufouchi
Said
S
Weill
Jean-Claude
JC
Reynaud
Claude-Agnès
CA
D000818:Animals; D001402:B-Lymphocytes; D020137:Base Pair Mismatch; D001483:Base Sequence; D004260:DNA Repair; D004259:DNA-Directed DNA Polymerase / Q000172:deficiency* / Q000235:genetics; D005803:Genes, Immunoglobulin; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D010581:Peyer's Patches; D027041:Somatic Hypermutation, Immunoglobulin; D000094769:DNA Polymerase iota; D000099270:Y-Family DNA Polymerases
D004259:DNA-Directed DNA Polymerase; D000094769:DNA Polymerase iota; C112338:Rad30 protein; D000099270:Y-Family DNA Polymerases