TY - JOUR
T1 - Regulation of DNA metabolic enzymes upon induction of preB cell development and V(D)J recombination
T2 - Up-regulation of DNA polymerase δ
AU - Jessberger, Rolf
AU - Schär, Primo
AU - Robins, Peter
AU - Ferrari, Elena
AU - Riwar, Brigitte
AU - Hübscher, Ulrich
N1 - Funding Information:
The authors wish to thank Dr Tomas Lindahl for discussions and critical reading the manuscript, Drs Antonius Rolink and Alexandre T.Akhmedov for critical reading of the manuscript and Graham Daly for technical assistance in the ligation assays. E.F. and U.H. are supported by the Kanton of Zürich. The Basel Institute for Immunology was founded and is supported by Hoffmann-LaRoche Inc., Switzerland.
PY - 1997
Y1 - 1997
N2 - Withdrawal of interleukin-7 from cultured murine preB lymphocytes induces cell differentiation including V(D)J immunoglobulin gene rearrangements and cell cycle arrest. Advanced steps of the V(D)J recombination reaction involve processing of coding ends by several largely unidentified DNA metabolic enzymes. We have analyzed expression and activity of DNA polymerases α, β, δ and ε, proliferating cell nuclear antigen (PCNA), topoisomerases I and II, terminal deoxynucleotidyl transferase (TdT) and DNA ligases I, III and IV upon induction of preB cell differentiation. Despite the immediate arrest of cell proliferation, DNA polymerase δ protein levels remained unchanged for ~ 2 days and its activity was up-regulated several-fold, while PCNA was continuously present. Activity of DNA polymerases α, β and ε decreased. Expression and activity of DNA ligase I were drastically reduced, while those of DNA ligases III and IV remained virtually constant. No changes in DNA topoisomerases I or II expression and activity occurred and TdT expression was moderately increased early after induction. Our results render DNA polymerase δ a likely candidate acting in DNA synthesis related to V(D)J recombination in lymphocytes.
AB - Withdrawal of interleukin-7 from cultured murine preB lymphocytes induces cell differentiation including V(D)J immunoglobulin gene rearrangements and cell cycle arrest. Advanced steps of the V(D)J recombination reaction involve processing of coding ends by several largely unidentified DNA metabolic enzymes. We have analyzed expression and activity of DNA polymerases α, β, δ and ε, proliferating cell nuclear antigen (PCNA), topoisomerases I and II, terminal deoxynucleotidyl transferase (TdT) and DNA ligases I, III and IV upon induction of preB cell differentiation. Despite the immediate arrest of cell proliferation, DNA polymerase δ protein levels remained unchanged for ~ 2 days and its activity was up-regulated several-fold, while PCNA was continuously present. Activity of DNA polymerases α, β and ε decreased. Expression and activity of DNA ligase I were drastically reduced, while those of DNA ligases III and IV remained virtually constant. No changes in DNA topoisomerases I or II expression and activity occurred and TdT expression was moderately increased early after induction. Our results render DNA polymerase δ a likely candidate acting in DNA synthesis related to V(D)J recombination in lymphocytes.
UR - https://www.scopus.com/pages/publications/0030771156
U2 - 10.1093/nar/25.2.289
DO - 10.1093/nar/25.2.289
M3 - Article
C2 - 9016556
AN - SCOPUS:0030771156
SN - 0305-1048
VL - 25
SP - 289
EP - 296
JO - Nucleic Acids Research
JF - Nucleic Acids Research
IS - 2
ER -