CALMODULIN IS INVOLVED IN THE INDUCTION OF DNA-POLYMERASE-ALPHA AND DNA-POLYMERASE-DELTA ACTIVITIES IN NORMAL RAT-KIDNEY CELLS ACTIVATED TOPROLIFERATE

Normal rat kidney cells that reenter the cell cycle from quiescence st art DNA synthesis at 12 h following serum addition and reach a maximum after 20 h. We have previously shown that the activation of DNA polym erase alpha, and the expression of the proliferating cell nuclear anti gen were inhibited when the anti-calmodulin drug W13 is added to the c ell cultures. Here we have analyzed the effect of W13 on the activity of DNA polymerase delta and on the expression of replication protein A . The results showed that the blockade of calmodulin by W13 produced a n almost complete inhibition of DNA polymerase delta activity whereas the activity of DNA polymerase a was only partially inhibited. Finally , the expression of replication protein A was not affected after W13 t reatment. Our data suggest that calmodulin might regulate DNA replicat ion through the control of the activities of DNA polymerases alpha and delta and the expression of proliferating cell nuclear antigen. (C) 1 995 Academic Press, Inc.