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

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

Research output: Contribution to journalArticlepeer-review

16 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)289-296
Number of pages8
JournalNucleic Acids Research
Volume25
Issue number2
DOIs
StatePublished - 1997
Externally publishedYes

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