Cis-acting negative control of DNA replication in eukaryotic cells.
We show that in stable monkey cell lines, the replication of a chimeric SV40-BPV episomal replicon occurs once and only once per cell cycle. The copy number of this episome is stably maintained even when an excess of the limiting initiation factor T antigen is provided. These experiments therefore uncover a cis-acting negative control mechanism whereby replication control is not focused on limiting the activity of positive factors; rather, replication is permitted in unreplicated replicons but is actively prevented, in cis, in replicons that have already been duplicated. We also find that the initiation factor SV40 T antigen remains associated with its SV-BPV episomal template in a kinetically stable and potentially heritable state.
Roberts
J M
JM
Division of Basic Sciences, Fred Hutchinson Cancer Center, Seattle, Washington 98104.
Weintraub
H
H
D000818:Animals; D000957:Antigens, Viral, Tumor / Q000235:genetics; D052688:Bovine papillomavirus 1 / Q000235:genetics; D002453:Cell Cycle; D002460:Cell Line; D004261:DNA Replication; D005822:Genetic Vectors; D010957:Plasmids; D012093:Replicon; D013539:Simian virus 40 / Q000235:genetics; D014158:Transcription, Genetic; D014162:Transfection; D014779:Virus Replication
D000957:Antigens, Viral, Tumor