DNA polymerase η is the sole contributor of A/T modifications during immunoglobulin gene hypermutation in the mouse
| Autor: | Said Aoufouchi, Frédéric Delbos, Jean-Claude Weill, Claude-Agnès Reynaud, Ahmad Faili |
|---|---|
| Přispěvatelé: | Développement du Systeme Immunitaire, Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Ligue Nationale Contre le Cancer, Fondation Princesse Grace de Monaco, Delbos, Frédéric, Université Paris Descartes - Paris 5 (UPD5) - Institut National de la Santé et de la Recherche Médicale (INSERM) - Centre National de la Recherche Scientifique (CNRS) |
| Rok vydání: | 2006 |
| Předmět: |
MESH: Somatic Hypermutation
Immunoglobulin [SDV.IMM] Life Sciences [q-bio]/Immunology Mismatch repair complex DNA polymerase MESH: Base Pairing Immunology Somatic hypermutation DNA-Directed DNA Polymerase DNA polymerase eta DNA Mismatch Repair MESH: Mice Knockout MESH: Models Immunological MESH: MutS Homolog 2 Protein Mice 03 medical and health sciences 0302 clinical medicine MESH: DNA-Directed DNA Polymerase Animals Immunology and Allergy MESH: Animals MESH: Models Genetic DNA Polymerase Kappa Base Pairing MESH: Mice 030304 developmental biology Mice Knockout 0303 health sciences Models Genetic biology Models Immunological Brief Definitive Report MESH: DNA DNA DNA Repair Pathway Molecular biology somatic hypermutation MutS Homolog 2 Protein MESH: DNA Mismatch Repair DNA glycosylase immunoglobulin genes biology.protein Brief Definitive Reports polymerase eta [SDV.IMM]Life Sciences [q-bio]/Immunology DNA mismatch repair Somatic Hypermutation Immunoglobulin 030215 immunology |
| Zdroj: | Journal of Experimental Medicine Journal of Experimental Medicine, Rockefeller University Press, 2007, 204 (1), pp.17-23. ⟨10.1084/jem.20062131⟩ Journal of Experimental Medicine, 2007, 204 (1), pp.17-23. ⟨10.1084/jem.20062131⟩ The Journal of Experimental Medecine The Journal of Experimental Medecine, The Rockefeller University Press, 2007, 204 (1), pp.17-23. 〈10.1084/jem.20062131〉 The Journal of Experimental Medicine |
| ISSN: | 1540-9538 0022-1007 |
| DOI: | 10.1084/jem.20062131 |
| Popis: | International audience; Mutations at A/T bases within immunoglobulin genes have been shown to be generated by a repair pathway involving the DNA-binding moiety of the mismatch repair complex constituted by the MSH2-MSH6 proteins, together with DNA polymerase eta (pol eta). However, residual A/T mutagenesis is still observed upon inactivation in the mouse of each of these factors, suggesting that the panel of activities involved might be more complex. We reported previously (Delbos, F., A. De Smet, A. Faili, S. Aoufouchi, J.-C. Weill, and C.-A. Reynaud. 2005. J. Exp. Med. 201:1191-1196) that residual A/T mutagenesis in pol eta-deficient mice was likely contributed by another enzyme not normally involved in hypermutation, DNA polymerase kappa, which is mobilized in the absence of the normal polymerase partner. We report the complete absence of A/T mutations in MSH2-pol eta double-deficient mice, thus indicating that the residual A/T mutagenesis in MSH2-deficient mice is contributed by pol eta, now recruited by uracil N-glycosylase, the second DNA repair pathway involved in hypermutation. We propose that this particular recruitment of pol eta corresponds to a profound modification of the function of uracil glycosylase in the absence of the mismatch repair complex, suggesting that MSH2-MSH6 actively prevent uracil glycosylase from error-free repair during hypermutation. pol eta thus appears to be the sole contributor of A/T mutations in the normal physiological context. |
| Databáze: | OpenAIRE |
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