Interactions of the papovavirus DNA replication initiator proteins, bovine papillomavirus type 1 E1 and simian virus 40 large T antigen, with human replication protein A.
Papovaviruses utilize predominantly cellular DNA replication proteins to replicate their own viral genomes. To appropriate the cellular DNA replication machinery, simian virus 40 (SV40) large T antigen (Tag) binds to three different cellular replication proteins, the DNA polymerase alpha-primase complex, the replication protein A (RPA) complex, and topoisomerase I. The functionally similar papillomavirus E1 protein has also been shown to bind to the DNA polymerase alpha-primase complex. Enzyme-linked immunoassay-based protein interaction assays and protein affinity pull-down assays were used to show that the papillomavirus E1 protein also binds to the cellular RPA complex in vitro. Furthermore, SV40 Tag was able to compete with bovine papillomavirus type 1 E1 for binding to RPA. Each of the three RPA subunits was individually overexpressed in Escherichia coli as a soluble fusion protein. These fusion proteins were used to show that the E1-RPA and Tag-RPA interactions are primarily mediated through the 70-kDa subunit of RPA. These results suggest that different viruses have evolved similar mechanisms for taking control of the cellular DNA replication machinery.
Han
Y
Y
Department of Microbiology and Center for Microbial Pathogenesis, School of Medicine and Biomedical Sciences, State University of New York at Buffalo, New York, USA.
Loo
Y M
YM
Militello
K T
KT
Melendy
T
T
D000952:Antigens, Polyomavirus Transforming / Q000502:physiology*; D004265:DNA Helicases / Q000502:physiology*; D004261:DNA Replication; D004268:DNA-Binding Proteins / Q000502:physiology*; D006801:Humans; D051716:Replication Protein A; D013539:Simian virus 40 / Q000276:immunology*; D015534:Trans-Activators / Q000502:physiology*; D014764:Viral Proteins / Q000502:physiology*; D014779:Virus Replication
D000952:Antigens, Polyomavirus Transforming; D004268:DNA-Binding Proteins; C069814:E1 protein, Bovine papillomavirus; C497167:RPA1 protein, human; D051716:Replication Protein A; D015534:Trans-Activators; D014764:Viral Proteins; C045264:replication initiator protein; D004265:DNA Helicases