TY - JOUR
T1 - Contribution of DNA polymerase η to immunoglobulin gene hypermutation in the mouse
AU - Delbos, Frédéric
AU - De Smet, Annie
AU - Faili, Ahmad
AU - Aoufouchi, Said
AU - Weill, Jean Claude
AU - Reynaud, Claude Agnès
PY - 2005/4/18
Y1 - 2005/4/18
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=18244401095&partnerID=8YFLogxK
U2 - 10.1084/jem.20050292
DO - 10.1084/jem.20050292
M3 - Article
C2 - 15824086
AN - SCOPUS:18244401095
SN - 0022-1007
VL - 201
SP - 1191
EP - 1196
JO - Journal of Experimental Medicine
JF - Journal of Experimental Medicine
IS - 8
ER -