How Does SV40 T Antigen Control Initiation of Viral DNA Replication

Simian virus 40 (SV40) large T antigen is a multifunctional protein involved in the regulation of viral transcription and DNA replication in lytically infected monkey cells and in the establishment and maintenance of cell transformation by SV40 (1). T antigen occurs in several different forms which differ biologically and biochemically. T antigen binds specifically to several sites in the origin region of SV40 DNA, acts as an ATPase and associates stably with a transformation- and cell cycle-related cellular phosphoprotein p53 (1). Yet how these properties enable this remarkable protein to fulfill its many varied functions remains unknown. This communication summarizes the biochemical properties of different forms of T antigen from two groups of mutants defective in initiation of SV40 DNA replication, as compared with those of wild-type T antigen. Based on these results, we suggest a possible mechanism for T antigen function in the initiation of SV40 DNA replication and present the results of initial experiments designed to test this model.