DNA polymerase kappa deficiency does not affect somatic hypermutation in mice.
Somatic hypermutation (SH) in B cells undergoing T cell-dependent immune responses generates high-affinity antibodies that provide protective immunity. Most current models of SH postulate the introduction of a nick into the DNA and subsequent replication-independent, error-prone short-patch synthesis by one or more DNA polymerases. The Pol kappa (DinB1) gene encodes a specialized mammalian DNA polymerase called DNA polymerase kappa (pol kappa), a member of the recently discovered Y family of DNA polymerases. The mouse PolK gene is expressed at high levels in the seminiferous tubules of the testis and in the adrenal cortex, and at lower levels in most other cells of the body including B lymphocytes. In vitro studies showed that pol kappa can act as an error-prone polymerase, although they failed to ascribe a clear function to this enzyme. The ability of pol kappa to generate mutations when extending primers on undamaged DNA templates identifies this enzyme as a potential candidate for the introduction of nucleotide changes in the immunoglobulin (Ig) genes during the process of SH. Here we show that pol kappa-deficient mice are viable, fertile and able to mount a normal immune response to the antigen (4-hydroxy-3-nitrophenyl)acetyl-chicken gamma-globulin (NP-GC). They also mutate their Ig genes normally. However, pol kappa-deficient embryonic fibroblasts are abnormally sensitive to killing following exposure to ultraviolet (UV) radiation, suggesting a role of pol kappa in translesion DNA synthesis.
Schenten
Dominik
D
Institute for Genetics, University of Cologne, Cologne, Germany.
Gerlach
Valerie L
VL
Guo
Caixia
C
Velasco-Miguel
Susana
S
Hladik
Christa L
CL
White
Charles L
CL
Friedberg
Errol C
EC
Rajewsky
Klaus
K
Esposito
Gloria
G
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D004259:DNA-Directed DNA Polymerase / Q000172:deficiency / Q000502:physiology*; D005298:Fertility; D005347:Fibroblasts / Q000528:radiation effects; D018858:Germinal Center / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D027041:Somatic Hypermutation, Immunoglobulin; D014466:Ultraviolet Rays; D000099270:Y-Family DNA Polymerases
D004259:DNA-Directed DNA Polymerase; C498613:Polk protein, mouse; D000099270:Y-Family DNA Polymerases