title: Two E2 binding sites alone are sufficient to function as the minimal origin of replication of human papillomavirus type 18 DNA.
abstract: Replication of papillomaviruses requires an origin of replication and two virus-encoded proteins, E1 and E2. Using a transient replication assay for human papillomavirus type 18 (HPV-18) DNA, we have found that two adjacent sequences present within the origin of replication can independently support replication. The first, a 77-bp region, contains one E2 binding site (E2BS) and a 16-bp inverted repeat element that probably corresponds to the E1 binding site (E1BS). The other, an 81-bp region, includes two E2BS but lacks the putative E1BS. A synthetic 33-bp oligonucleotide containing two high-affinity E2BS was also found to function as an origin of replication. Replication of all these plasmids was absolutely dependent on the presence of the HPV-18 E1 and E2 proteins. The HPV-1a E1 and E2 proteins were also found to support replication of a plasmid containing the complete HPV-18 origin but failed to replicate a plasmid containing two E2BS alone. Our results suggest that the E2 protein can target E1 to the origin through the formation of an E1-E2 complex which is likely to be involved the initiation of replication.
authors: Department of Molecular Genetics and Biochemistry, University of Pittsburgh School of Medicine, Pennsylvania 15261.
authors: F
authors: F
authors: Sverdrup
authors: S A
authors: SA
authors: Khan
mesh_terms: D001483:Base Sequence; D001665:Binding Sites; D004261:DNA Replication; D008969:Molecular Sequence Data; D009856:Oncogene Proteins, Viral / Q000502:physiology*; D027383:Papillomaviridae / Q000235:genetics*; D010957:Plasmids; D014779:Virus Replication
chemical_list: D009856:Oncogene Proteins, Viral; C084762:oncogene protein E1, Human papillomavirus type 18; C069102:oncogene protein E2, Human papillomavirus type 18