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Contribution of DNA polymerase to immunoglobulin gene hypermutation in the mouse

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

CORRESPONDENCE Claude-Agnès Reynaud: reynaud{at}necker.fr OR Jean-Claude Weill: weill{at}necker.fr

The mutation pattern of immunoglobulin genes was studied in mice deficient for DNA polymerase , 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 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-deficient mice differs markedly. This suggests that, in the absence of pol, the MSH2–MSH6 complex is able to recruit another DNA polymerase that is more accurate at copying A/T bases, possibly pol, to assume its function in hypermutation.

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