TY - JOUR
T1 - DNA Polymerase η Is Involved in Hypermutation Occurring during Immunoglobulin Class Switch Recombination
AU - Faili, Ahmad
AU - Aoufouchi, Said
AU - Weller, Sandra
AU - Vuillier, Françoise
AU - Stary, Anne
AU - Sarasin, Alain
AU - Reynaud, Claude Agnès
AU - Weill, Jean Claude
PY - 2004/1/19
Y1 - 2004/1/19
N2 - Base substitutions, deletions, and duplications are observed at the immunoglobulin locus in DNA sequences involved in class switch recombination (CSR.) These mutations are dependent upon activation-induced cytidine deaminase (AID) and present all the characteristics of the ones observed during V gene somatic hypermutation, implying that they could be generated by the same mutational complex. It has been proposed, based on the V gene mutation pattern of patients with the cancer-prone xeroderma pigmentosum variant (XP-V) syndrome who are deficient in DNA polymerase η (pol η), that this enzyme could be responsible for a large part of the mutations occurring on A/T bases. Here we show, by analyzing switched memory B cells from two XP-V patients, that pol η is also an A/T mutator during CSR, in both the switch region of tandem repeats as well as upstream of it, thus suggesting that the same error-prone translesional polymerases are involved, together with AID, in both processes.
AB - Base substitutions, deletions, and duplications are observed at the immunoglobulin locus in DNA sequences involved in class switch recombination (CSR.) These mutations are dependent upon activation-induced cytidine deaminase (AID) and present all the characteristics of the ones observed during V gene somatic hypermutation, implying that they could be generated by the same mutational complex. It has been proposed, based on the V gene mutation pattern of patients with the cancer-prone xeroderma pigmentosum variant (XP-V) syndrome who are deficient in DNA polymerase η (pol η), that this enzyme could be responsible for a large part of the mutations occurring on A/T bases. Here we show, by analyzing switched memory B cells from two XP-V patients, that pol η is also an A/T mutator during CSR, in both the switch region of tandem repeats as well as upstream of it, thus suggesting that the same error-prone translesional polymerases are involved, together with AID, in both processes.
KW - Pol η
KW - Somatic mutation
KW - Translesional DNA polymerases
KW - Xeroderma pigmentosum variant syndrome
UR - http://www.scopus.com/inward/record.url?scp=1642499721&partnerID=8YFLogxK
U2 - 10.1084/jem.20031831
DO - 10.1084/jem.20031831
M3 - Article
C2 - 14734526
AN - SCOPUS:1642499721
SN - 0022-1007
VL - 199
SP - 265
EP - 270
JO - Journal of Experimental Medicine
JF - Journal of Experimental Medicine
IS - 2
ER -