A neutralizing antibody against human DNA polymerase ε inhibits cellular but not SV40 DNA replication

The contribution of human DNA polymerase ε to nuclear DNA replication was studied. Antibody K18 that specifically inhibits DNA polymerase activity of human DNA polymerase ε in vitro significantly inhibits DNA synthesis both when microinjected into nuclei of exponentially growing human fibroblasts and in isolated HeLa cell nuclei. The capability of this neutralizing antibody to inhibit DNA synthesis in cells is comparable to that of monoclonal antibody SJK-132-20 against DNA polymerase α. Contrary to the antibody against DNA polymerase α, antibody K18 against DNA polymerase ε did not inhibit SV40 DNA replication in vitro. These results indicate that DNA polymerase ε plays a role in replicative DNA synthesis in proliferating human cells like DNA polymerase α, and that this role for DNA polymerase ε cannot be modeled by SV40 DNA replication.