TY - JOUR
T1 - The translesion DNA polymerase ζ plays a major role in Ig and bcl-6 somatic hypermutation
AU - Zan, Hong
AU - Komori, Atsumasa
AU - Li, Zongdong
AU - Cerutti, Andrea
AU - Schaffer, András
AU - Flajnik, Martin F.
AU - Diaz, Marilyn
AU - Casali, Paolo
N1 - Copyright:
Copyright 2018 Elsevier B.V., All rights reserved.
PY - 2001
Y1 - 2001
N2 - Ig somatic mutations would be introduced by a polymerase (pol) while repairing DNA outside main DNA replication. We show that human B cells constitutively express the translesion pol ζ, which effectively extends DNA past mismatched bases (mispair extender), and pol η, which bypasses DNA lesions in an error-free fashion. Upon B cell receptor (BCR) engagement and coculture with activated CD4+ T cells, these lymphocytes upregulated pol ζ, downregulated pol η, and mutated the Ig and bcl-6 genes. Inhibition of the pol ζ REV3 catalytic subunit by specific phosphorothioate-modified oligonucleotides impaired Ig and bcl-6 hypermutation and UV damage-induced DNA mutagenesis, without affecting cell cycle or viability. Thus, pol ζ plays a critical role in Ig and bcl-6 hypermutation, perhaps facilitated by the downregulation of pol η.
AB - Ig somatic mutations would be introduced by a polymerase (pol) while repairing DNA outside main DNA replication. We show that human B cells constitutively express the translesion pol ζ, which effectively extends DNA past mismatched bases (mispair extender), and pol η, which bypasses DNA lesions in an error-free fashion. Upon B cell receptor (BCR) engagement and coculture with activated CD4+ T cells, these lymphocytes upregulated pol ζ, downregulated pol η, and mutated the Ig and bcl-6 genes. Inhibition of the pol ζ REV3 catalytic subunit by specific phosphorothioate-modified oligonucleotides impaired Ig and bcl-6 hypermutation and UV damage-induced DNA mutagenesis, without affecting cell cycle or viability. Thus, pol ζ plays a critical role in Ig and bcl-6 hypermutation, perhaps facilitated by the downregulation of pol η.
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U2 - 10.1016/S1074-7613(01)00142-X
DO - 10.1016/S1074-7613(01)00142-X
M3 - Article
C2 - 11371365
AN - SCOPUS:0035005241
VL - 14
SP - 643
EP - 653
JO - Immunity
JF - Immunity
SN - 1074-7613
IS - 5
ER -