Contribution of DNA polymerase η to immunoglobulin gene hypermutation in the mouse

Frédéric Delbos, Annie De Smet, Ahmad Faili, Said Aoufouchi, Jean Claude Weill, Claude Agnès Reynaud

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    Résumé

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

    langue originaleAnglais
    Pages (de - à)1191-1196
    Nombre de pages6
    journalJournal of Experimental Medicine
    Volume201
    Numéro de publication8
    Les DOIs
    étatPublié - 18 avr. 2005

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