INHIBITION OF CELLULAR AND SV40 DNA-REPLICATION BY THE ADENOASSOCIATED VIRUS REP PROTEINS

In order to define the mechanism used by the adeno-associated virus re plication (rep) gene to mediate inhibition of cell proliferation, we h ave studied its effects on SV40 and cellular DNA replication. SV40 DNA replication was inhibited by the presence of the rep gene in human 29 3 cells, and the inhibition was not linked to suppression of SV40 earl y gene expression. Using double-immunofluorescence assays that measure d both rep gene expression and bromodeoxyuridine incorporation, we fou nd that the presence of the Rep78 and Rep68 proteins correlated with i nhibition of cellular DNA synthesis in NIH3T3 cells. This links the re p gene's anti-proliferative effects to either: (i) a direct inhibition of DNA synthesis or (ii) a possible cell cycle block. (C) 1995 Academ ic Press, Inc.