Inhibition of DNA replication and DNA polymerase .alpha. activity by monoclonal anti-(DNA polymerase .alpha.) IgG and F(ab) fragments

Publisher Website
Google Scholar
Abstract
The effect of monoclonal anti-(DNA polymerase .alpha.) immunoglobulin G (IgG) and F(ab) fragments on DNA replacation in lysolecithin-permeabilized human cells and on DNA polymerase .alpha. activity was determined. DNA polymerase .alpha. activity in vitro was inhibited equally by the same concentrations of monoclonal IgGs and F(ab) fragments. However, the IgGs and F(ab) fragments were not equally potent in inhibiting DNA replication in permeable cells. In general, the F(ab) fragments were .simeq. 10-fold more potent than IgGs in inhibiting DNA replication, suggesting the F(ab) fragments cross the nuclear membrane more readily than IgGs. Immunocytochemical studies demonstrated that at least a fraction of anti-(DNA polymerase .alpha.) IgGs entered the nulceus of permeable cells. For most antibodies tested, the IgG or F(ab) concentration needed to inhibit replication was several orders of magnitude higher than that needed to neutralize polymerase .alpha. activity extracted from the same number of cells. Anti-(DNA polymerase .alpha.) F(ab) fragments were shown to inhibit the discontinuous synthesis of Okazaki DNA, as well as the maturation of Okazaki DNA to larger DNA, thereby implicating DNA polymerase .alpha. in both of these processes.

This publication has 21 references indexed in Scilit: