REGULATION OF DNA METABOLIC ENZYMES UPON INDUCTION OF PREB CELL-DEVELOPMENT AND V(D)J RECOMBINATION - UP-REGULATION OF DNA-POLYMERASE-DELTA

Withdrawal of interleukin-7 from cultured murine preB lymphocytes indu ces cell differentiation including V(D)J immunoglobulin gene rearrange ments and cell cycle arrest, Advanced steps of the V(D)J recombination reaction involve processing of coding ends by several largely unident ified DNA metabolic enzymes, We have analyzed expression and activity of DNA polymerases alpha, beta, delta and epsilon, proliferating cell nuclear antigen (PCNA), topoisomerases and II, terminal deoxynucleotid yl transferase (TdT) and DNA ligases I, III and IV upon induction of p reB cell differentiation, Despite the immediate arrest of cell prolife ration, DNA polymerase delta protein levels remained unchanged for sim ilar to 2 days and its activity was up-regulated several-fold, while P CNA was continuously present, Activity of DNA polymerases alpha, beta and epsilon decreased, Expression and activity of DNA ligase I were dr astically reduced, while those of DNA ligases III and IV remained virt ually constant, No changes in DNA topoisomerases I or II expression an d activity occurred and TdT expression was moderately increased early after induction, Our results render DNA polymerase delta a likely cand idate acting in DNA synthesis related to V(D)J recombination in lympho cytes.