title: Papillomavirus contains cis-acting sequences that can suppress but not regulate origins of DNA replication.
abstract: Bovine papillomavirus (BPV) DNA has been reported to restrict its own replication and that of the lytic simian virus 40 (SV40) origin to one initiation event per molecule per S phase, which suggests BPV DNA replication as a model for cellular chromosome replication. Suppression of the SV40 origin required two cis-acting BPV sequences (NCOR-1 and -2) and one trans-acting BPV protein. The results presented in this paper confirm the presence of two NCOR sequences in the BPV genome that can suppress polyomavirus (PyV) as well as SV40 origin-dependent DNA replication as much as 40-fold. However, in contrast to results of previous studies on SV40, most of the suppression of the PyV origin was due to NCOR-1, a 512-bp sequence that functioned independently of distance or orientation with respect to the PyV origin and that was not required for BPV DNA replication. Moreover, NCOR-1 alone or together with NCOR-2 did not restrict the ability of the PyV ori to reinitiate replication within a single S phase and did not require any BPV protein to exert suppression. Furthermore, NCOR-1 did not suppress BPV origin-dependent DNA replication except in the presence of PyV large tumor antigen (T-ag). Since NCOR-1 suppression of PyV origin activity also varied with T-ag concentration, suppression of origins by NCOR sequences appeared to require papovavirus T-ag. Therefore, it is unlikely that NCOR sequences are involved in regulating BPV DNA replication. When these results are taken together with those from other laboratories, BPV appears to be a slowly replicating version of papovaviruses rather than a model for origins of DNA replication in eukaryotic cell chromosomes.
authors.affiliation: Roche Institute of Molecular Biology, Roche Research Center, Nutley, New Jersey 07110.
authors.forename: F S
authors.initials: FS
authors.lastname: Nallaseth
authors.forename: M L
authors.initials: ML
authors.lastname: DePamphilis
mesh_terms: D000957:Antigens, Viral, Tumor / Q000494:pharmacology; D052688:Bovine papillomavirus 1 / Q000235:genetics* / Q000254:growth & development*; D004252:DNA Mutational Analysis; D004261:DNA Replication / Q000187:drug effects / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000378:metabolism; D018274:Electroporation; D027383:Papillomaviridae / Q000276:immunology; D010957:Plasmids / Q000235:genetics; D027382:Polyomaviridae; D011120:Polyomavirus / Q000235:genetics; D012045:Regulatory Sequences, Nucleic Acid; D016196:S Phase; D017384:Sequence Deletion; D013489:Suppression, Genetic; D014764:Viral Proteins / Q000378:metabolism
chemical_list: D000957:Antigens, Viral, Tumor; D004268:DNA-Binding Proteins; C069814:E1 protein, Bovine papillomavirus; C051550:E2 protein, Bovine papillomavirus; D014764:Viral Proteins