Abstract
The mechanism of SV40 DNA replication is certainly not completely understood. The proteins that are necessary for replication have been known for quite some time, but how they work together to form a nanomachine capable of faithfully replicating the virus DNA is only partially understood. Some of the proteins involved have been crystallized and their 3D structures determined, and several EM reconstructions of SV40 T antigen have been generated. In addition, there is a fair amount of biochemical data that pinpoints the sites of interaction between various proteins. With this information, various models were assembled that show how the SV40 DNA replication nanomachine could be structured in three dimensional space. This process was aided by the use of a 3D docking program as well as fitting of structures. The advantage of the availability of these models is that they are experimentally testable and they provide an insight into how the replication machine could work. Another advantage is that it is possible to quickly compare newly published structures to the models in order to come up with improved models.
Highlights
It has been clearly documented that the SV40 large T antigen forms a structure that acts as a scaffold for the construction of the viral replication factory [1±3]
The salient features are that the DNA binding domains of individual monomers recognize and bind to each of the four GAGGC pentanucleotide sequences that make up the center of the origin and in this way nucleate the formation of a double hexamer
Since the origin binding domains of T antigen initiate the formation of the double hexamer (DH) and since they are thought to attach in a head to head fashion in the center of the DH, they were a good starting point for the construction of the replication models
Summary
It has been clearly documented that the SV40 large T antigen forms a structure that acts as a scaffold for the construction of the viral replication factory [1±3]. The helicase domains are used to make contacts with the flanking origin sequences (the EP region and AT tract) [8] and, through subunit contacts, drive the formation of two hexameric helicases that contain a central channel through which DNA flows. This structure can form by itself over DNA. It was the focus of this paper to develop models of how the DH functions as a helicase and how the ensuing replication factory could form and work
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