Polyomavirus large T can support DNA replication in human cells.
Human cells are generally thought to be nonpermissive for polyomavirus (Py) DNA replication. Using transient transfection, we show that Py large T-antigen (LT) was able to support replication of a Py origin-containing plasmid in two human cell lines. Replication supported by LT in human cells was specific for the Py origin and required its enhancer sequences, as well as the previously reported critical phosphorylation sites within LT. Py replication efficiency was comparable to that of papillomavirus E1 and E2 activated DNA replication in transient assays performed in human 293 and C-33A cells. Previous analysis of DNA replication in vitro has pointed to polymerase alpha-primase as a specificity determinant for polyomavirus. The data presented here imply that in certain cellular environments, Py LT must functionally interact with human polymerase alpha-primase to permit DNA replication.
Sverdrup
F
F
Department of Dermatology, New England Medical Center, Boston, MA 02111, USA.
Schaffhausen
B S
BS
Androphy
E J
EJ
D016475:3T3 Cells; D000818:Animals; D000952:Antigens, Polyomavirus Transforming / Q000502:physiology*; D052688:Bovine papillomavirus 1 / Q000235:genetics / Q000502:physiology*; D002460:Cell Line; D002522:Chlorocebus aethiops; D003587:Cytomegalovirus / Q000235:genetics; D019915:DNA Primase / Q000378:metabolism; D004261:DNA Replication; D004279:DNA, Viral / Q000096:biosynthesis; D005260:Female; D006801:Humans; D051379:Mice; D011120:Polyomavirus / Q000235:genetics / Q000502:physiology*; D011401:Promoter Regions, Genetic; D013539:Simian virus 40 / Q000235:genetics / Q000502:physiology*; D014407:Tumor Cells, Cultured; D002583:Uterine Cervical Neoplasms; D014779:Virus Replication
D000952:Antigens, Polyomavirus Transforming; D004279:DNA, Viral; D019915:DNA Primase