title: Contribution of DNA polymerase eta to immunoglobulin gene hypermutation in the mouse.
abstract: 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.
authors.affiliation: 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.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Delbos
authors.forename: Annie
authors.initials: A
authors.lastname: De Smet
authors.forename: Ahmad
authors.initials: A
authors.lastname: Faili
authors.forename: Said
authors.initials: S
authors.lastname: Aoufouchi
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Weill
authors.forename: Claude-Agnès
authors.initials: CA
authors.lastname: Reynaud
mesh_terms: 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
chemical_list: D004259:DNA-Directed DNA Polymerase; D000094769:DNA Polymerase iota; C112338:Rad30 protein; D000099270:Y-Family DNA Polymerases