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Mouse p53 inhibits SV40 origin-dependent DNA replication

Abstract

p53 is a cellular phosphoprotein that is present at elevated concentrations in cells transformed by different agents1–5. p53 complementary DNA expression-constructs immortalize primary cells in vitro6,7 and co-operate with an activated ras oncogene in malignant transformation6,8,9. Several reports have implicated p53 in mammalian cell cycle control and specifically with events occurring at the G0–G1 boundary10,11. p53 forms specific complexes with simian virus 40 (SV40) large-T antigen1,2, and such complexes are found associated with both replicating and mature SV40 DNA in lytically infected cells12. In an accompanying paper Gannon and Lane13 report that in in vitro plate-binding assays, mouse p53 can displace polymerase α 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.

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Braithwaite, A., Sturzbecher, HW., Addison, C. et al. Mouse p53 inhibits SV40 origin-dependent DNA replication. Nature 329, 458–460 (1987). https://doi.org/10.1038/329458a0

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