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

The contribution of human DNA polymerase epsilon to nuclear DNA replication was studied. Antibody K18 that specifically inhibits DNA polymerase activi ty of human DNA polymerase epsilon in vitro significantly inhibits DNA synt hesis both when microinjected into nuclei of exponentially growing human fi broblasts and in isolated HeLa cell nuclei. The capability of this neutrali zing antibody to inhibit DNA synthesis in cells is comparable to that of mo noclonal antibody SJK-132-20 against DNA polymerase alpha. Contrary to the antibody against DNA polymerase alpha, antibody K18 against DNA polymerase epsilon did not inhibit SW40 DNA replication in vitro. These results indica te that DNA polymerase epsilon plays a role in replicative DNA synthesis in proliferating human cells like DNA polymerase alpha, and that this role fo r DNA polymerase epsilon cannot be modeled by SV40 DNA replication.