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Contribution of DNA polymerase eta to immunoglobulin gene hypermutation in the mouse.
Delbos F., De Smet A., Faili A., Aoufouchi S., Weill J.-C., Reynaud C.-A.
Journal of Experimental Medicine / The Journal of Experimental Medicine 201, 8 (2005) 1191-6 - http://www.hal.inserm.fr/inserm-00310380
 (15824086) 
Contribution of DNA polymerase eta to immunoglobulin gene hypermutation in the mouse.
Frédéric Delbos1, Annie De Smet1, Ahmad Faili1, Said Aoufouchi1, Jean-Claude Weill () 1, Claude-Agnès Reynaud () 1
1:  Developpement du Systeme Immunitaire
INSERM : U783 – Université Paris V - Paris Descartes
Fac de Medecine Necker-Enfants Malades PARIS V 156, Rue de Vaugirard 75730 PARIS CEDEX 15
France
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.
Life Sciences/Immunology
English
0022-1007

Article in peer-reviewed journal
10.1084/jem.20050292
Journal of Experimental Medicine / The Journal of Experimental Medicine
international
2005-04-18
2005-04-11
201
8
1191-6

immunoglobulin genes – somatic hypermutation – polymerase eta
Animals – B-Lymphocytes – Base Pair Mismatch – Base Sequence – DNA Repair – DNA-Directed DNA Polymerase – Genes – Immunoglobulin – Mice – Knockout – Molecular Sequence Data – Peyer's Patches – Somatic Hypermutation – Animals
Ministère de la Recherche (A.C.I. Biologie du Développement et Physiologie Intégrative); Ligue Nationale Contre le Cancer; Fondation Princesse Grace de Monaco
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