The Bovine Papillomavirus Origin of Replication Requires a Binding Site for the E2 Transcriptional Activator

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 90; no. 3; pp. 898 - 902
• Main Authors: USTAV, E, USTAV, M, SZYMANSKI, P, STENLUND, A
• Format: Journal Article
• Language: English
• Published: Washington, DC National Academy of Sciences of the United States of America 01-02-1993; National Acad Sciences; National Academy of Sciences
• Subjects: Base Sequence; Binding sites; Biochemistry; Biological and medical sciences; Bovine papillomavirus 1 - genetics; Bovine papillomavirus 1 - growth & development; Cattle; Cell lines; CHO cells; COS cells; Deoxyribonucleic acid; Dimerization; DNA; DNA Mutational Analysis; DNA Replication; DNA-Binding Proteins - metabolism; Enhancer Elements, Genetic - genetics; Fundamental and applied biological sciences. Psychology; Genetics; Microbiology; Molecular Sequence Data; Nucleic Acid Conformation; Plasmids; Replication origin; Structure-Activity Relationship; Transcription Factors - genetics; Transcription, Genetic; Ungulates; Viral Proteins - metabolism; Virology; Virus Replication; Viruses; Origin; Molecular interaction; Binding site; Papovaviridae; Mechanism; Papillomavirus; Virus; Regulation(control); DNA; Trans acting regulatory factor; Replication; Bovine papillomavirus 1; Transcription factor
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.90.3.898

The bovine papillomavirus type I transcriptional activator E2 is essential for replication of bovine papillomavirus DNA, yet most of the high-affinity binding sites for E2 are dispensable. Here we demonstrate an absolute requirement for a binding site for the E2 polypeptide as a cis-acting replication element, establishing that site-specific binding of E2 to the origin is a prerequisite for bovine papillomavirus replication in vivo. The position and distance of the E2 binding site relative to the other origin of replication components are flexible, but function at a distance requires high-affinity E2 binding sites. Thus, low-affinity binding sites function only when located close to the origin of replication, while activity at greater distances requires multimerized high-affinity E2 binding sites. The requirement for E2, although different in some respects, shows distinct similarities to what has been termed replication enhancers and may provide insight into the function of this class of DNA replication element.