Mouse p53 inhibits SV40 origin-dependent DNA replication.
p53 is a cellular phosphoprotein that is present at elevated concentrations in cells transformed by different agents. p53 complementary DNA expression-constructs immortalize primary cells in vitro and co-operate with an activated ras oncogene in malignant transformation. Several reports have implicated p53 in mammalian cell cycle control and specifically with events occurring at the G0-G1 boundary. p53 forms specific complexes with simian virus 40 (SV40) large-T antigen, and such complexes are found associated with both replicating and mature SV40 DNA in lytically infected cells. In an accompanying paper Gannon and Lane report that in in vitro plate-binding assays, mouse p53 can displace polymerase alpha from complex with T-antigen. We have examined the in vivo consequences of expressing wild-type and mutant p53 proteins from other species in SV40-transformed monkey cells. We report here that expression of mouse p53 results in a substantial and selective inhibition of SV40 origin-dependent DNA replication. In addition to any function in the G0-G1 transition, the data presented suggest that p53 may affect directly the initiation or maintenance of replicative DNA synthesis.
Braithwaite
A W
AW
Marie Curie Research Institute, Surrey, UK.
Sturzbecher
H W
HW
Addison
C
C
Palmer
C
C
Rudge
K
K
Jenkins
J R
JR
D000818:Animals; D000952:Antigens, Polyomavirus Transforming / Q000378:metabolism; D002460:Cell Line; D002472:Cell Transformation, Viral; D004257:DNA Polymerase II / Q000378:metabolism; D004261:DNA Replication; D004279:DNA, Viral / Q000096:biosynthesis*; D051379:Mice; D009363:Neoplasm Proteins / Q000235:genetics / Q000502:physiology*; D010750:Phosphoproteins / Q000235:genetics / Q000502:physiology*; D010957:Plasmids; D013539:Simian virus 40 / Q000235:genetics*; D014162:Transfection; D016159:Tumor Suppressor Protein p53
D000952:Antigens, Polyomavirus Transforming; D004279:DNA, Viral; D009363:Neoplasm Proteins; D010750:Phosphoproteins; D016159:Tumor Suppressor Protein p53; D004257:DNA Polymerase II