PAPILLOMAVIRUS CONTAINS CIS-ACTING SEQUENCES THAT CAN SUPPRESS BUT NOT REGULATE ORIGINS OF DNA-REPLICATION

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 rep lication as a model for cellular chromosome replication. Suppression o f the SV40 origin required two cis-acting BPV sequences (NCOR-1 and -2 ) and one trans-acting BPV protein. The results presented in this pape r confirm the presence of two NCOR sequences in the BPV genome that ca n suppress polyomavirus (PyV) as well as SV40 origin-dependent DNA rep lication as much as 40-fold. However, in contrast to results of previo us 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 requir ed for BPV DNA replication. Moreover, NCOR-1 alone or together with NC OR-2 did not restrict the ability of the PyV ori to reinitiate replica tion within a single S phase and did not require any BPV protein to ex ert suppression. Furthermore, NCOR-1 did not suppress BPV origin-depen dent DNA replication except in the presence of PyV large tumor antigen (T-ag). Since NCOR-1 suppression of PyV origin activity also varied w ith T-ag concentration, suppression of origins by NCOR sequences appea red to require papovavirus T-ag. Therefore, it is unlikely that NCOR s equences are involved in regulating BPV DNA replication. When these re sults are taken together with those from other laboratories, BPV appea rs to be a slowly replicating version of papovaviruses rather than a m odel for origins of DNA replication in eukaryotic cell chromosomes.