Relation of poly(adenosine diphosphoribose) synthesis to DNA synthesis and cell growth

Abstract

A permeable cell technique has been used to measure the synthesis of DNA and poly(adenosine diphosphoribose) (poly(ADPR)) in mouse L cells subjected to different perturbations of cell growth. Cells leaving log phase growth and entering plateau phase, showed a decrease in DNA synthesis and an associated increase in intrinsic poly(ADPR) synthesis. In contrast to the variations in intrinsic poly(ADPR) synthesis, the total poly(ADPR) synthesis activity, measured in the presence of added DNAase, remained relatively constant during the fluctuations in cell growth status. Cells subjected to acute glucose deficiency also demonstrated a decrease in DNA synthesis and an associated increase in intrinsic poly(ADPR) synthesis. Similarly, cells infected with vaccinia virus demonstrated an abrupt cessation of DNA synthesis associated with an increase in poly(ADPR) synthesis. Treatment of cells with cytosine arabinoside, inhibited cellular DNA synthesis. This was also associated with an increase in the intrinsic activity of poly(ADPR) synthesis. However, in this case, the increase in poly(ADPR) synthesis was associated with an increase in activity of the DNA synthesis complex, despite the overall inhibition of cell DNA synthesis. These studies demonstrate, that in mouse L cells, suppression of DNA synthesis by multiple different physiologic mechanisms is always associated with an increase in intrinsic activity of poly(ADPR) synthesis.