Inhibition of DNA replication factor RPA by p53.
The tumour suppressor p53 specifically interferes with the onset of S phase. The mechanism of the growth suppression action of the protein is unclear, though recent evidence points to transcriptional activation and repression functions of the protein. A competing hypothesis suggests that p53 interacts with the DNA replication apparatus and directly interferes with DNA replication. The major evidence for this hypothesis is that p53 interacts with the simian virus 40 (SV40)-encoded protein T antigen and interferes with the ability of T antigen to unwind the SV40 origin of DNA replication, and recruit DNA polymerase alpha to the replication initiation complex. Here we report that p53 physically interacts with and inhibits the function of a cellular DNA replication factor, the single-stranded DNA-binding protein complex RPA.
Dutta
A
A
Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115.
Ruppert
J M
JM
Aster
J C
JC
Winchester
E
E
D000952:Antigens, Polyomavirus Transforming / Q000378:metabolism; D001426:Bacterial Proteins / Q000235:genetics; D002460:Cell Line; D003001:Cloning, Molecular; D004247:DNA / Q000096:biosynthesis / Q000378:metabolism; D004261:DNA Replication / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D004926:Escherichia coli; D005978:Glutathione; D005982:Glutathione Transferase; D006801:Humans; D008863:Microspheres; D009154:Mutation; D011485:Protein Binding; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D051716:Replication Protein A; D016196:S Phase / Q000502:physiology; D012441:Saccharomyces cerevisiae; D012697:Serine Endopeptidases; D016159:Tumor Suppressor Protein p53 / Q000502:physiology*; D000099160:LexA Repressor Protein
D000952:Antigens, Polyomavirus Transforming; D001426:Bacterial Proteins; D004247:DNA; D004268:DNA-Binding Proteins; D005978:Glutathione; D005982:Glutathione Transferase; D011993:Recombinant Fusion Proteins; D051716:Replication Protein A; D012697:Serine Endopeptidases; D016159:Tumor Suppressor Protein p53; D000099160:LexA Repressor Protein; C497167:RPA1 protein, human