THE INITIATION OF SIMIAN-VIRUS-40 DNA-REPLICATION IN-VITRO

DNA replication is a complicated process that is largely regulated dur ing stages of initiation. The Siman Virus 40 in vitro replication syst em has served as an excellent model for studies of the initiation of D NA replication, and its regulation, in eukaryotes. Initiation of SV40 replication requires a single viral protein termed T-antigen, all othe r proteins are supplied by the host. The recent determination of the s olution structure of the T-antigen domain that recognizes the SV40 ori gin has provided significant insights into the initiation process. For example, it has afforded a clearer understanding of origin recognitio n, T-antigen oligomerization, and DNA unwinding. Furthermore, the Simi an virus 40 in vitro replication system has been used to study nascent DNA formation in the vicinity of the viral origin of replication. Amo ng the conclusions drawn from these experiments is that nascent DNA sy nthesis does not initiate in the core origin in vitro and that Okazaki fragment formation is complex. These and related studies demonstrate that significant progress has been made in understanding the initiatio n of DNA synthesis at the molecular level.