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Regulation of DNA metabolic enzymes upon induction of preB cell development and V(D)J recombination: up-regulation of DNA polymerase δ

Jessberger, Rolf ; Schär, Primo ; Robins, Peter ; Ferrari, Elena ; Riwar, Brigitte ; Hübscher, Ulrich

In: Nucleic Acids Research, 1997, vol. 25, no. 2, p. 289-296

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    Title
    • Regulation of DNA metabolic enzymes upon induction of preB cell development and V(D)J recombination: up-regulation of DNA polymerase δ
    Author
    • Jessberger, Rolf. Basel Institute for Immunology, Grenzacherstrasse 487, CH-4005 Basel, Switzerland, South Mimms, Herts EN6 3LD, UK, Winterthurerstrasse 190, CH-8057 Zürich, Switzerland
    • Schär, Primo. Basel Institute for Immunology, Grenzacherstrasse 487, CH-4005 Basel, Switzerland
    • Robins, Peter. Basel Institute for Immunology, Grenzacherstrasse 487, CH-4005 Basel, Switzerland
    • Ferrari, Elena. ICRF Laboratories, South Mimms, Herts EN6 3LD, UK
    • Riwar, Brigitte. Basel Institute for Immunology, Grenzacherstrasse 487, CH-4005 Basel, Switzerland, South Mimms, Herts EN6 3LD, UK, Winterthurerstrasse 190, CH-8057 Zürich, Switzerland
    • Hübscher, Ulrich. ICRF Laboratories, South Mimms, Herts EN6 3LD, UK
    Document Type
    • Postprint
    Language
    • English
    Published in
    • Nucleic Acids Research, 1997, vol. 25, no. 2, p. 289-296. Oxford University Press
    Other Version
    Classification
    • Health
    OAI-PMH Identifier
    • oai:doc.rero.ch:297514
    Summary
    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