The Replication Initiator Protein E1 and its Interaction with DNA

Cold Spring Harbor Laboratory, Cold Spg Hbr NY

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Abstract

DESCRIPTION (provided by applicant): Papillomaviruses are a large family of closely related viruses that give rise to warts in their hosts. Infection of the genital tract by the human viruses from this group represents one of the few firmly established links between viral infection and the development of cancer. The bovine papillomavirus, BPV, has served as a prototype for this group especially regarding viral DNA replication, but its relative simplicity serves also to examine mechanistic features of DNA replication in general. This system, whereby a single protein encompasses the key events in replication initiation through its different oligomeric forms, provides a great opportunity to examine these events in detail. Our goals are to build a mechanistic view of the assembly of E1 on the origin of replication and an understanding toward the workings of hexameric helicases in general at an atomic level. In addition, the viral DNA replication machinery itself represents an obvious target for antiviral therapy. Detailed information such as high-resolution structures of viral proteins required for replication will greatly facilitate the development and testing of antiviral agents. Relevance: infection of the genital tract by the human papillomaviruses represents one of the few firmly established links between viral infection and the development of cancer. The bovine papillomavirus, BPV, has served as a prototype for this group especially regarding viral replication. It also enables the understanding of key features in DNA replication in general due to its relative simplicity Our objective is to gain a mechanistic understanding of the events that initiate viral replication. This type of detailed information of viral proteins required for its replication and that can serve as targets for antiviral therapy, will greatly facilitate the development and testing of antiviral agents. Through there have been important recent advances in vaccine development, these may not be effective to a population that has already been infected.