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EMBO J
1995 May 01;149:2099-105. doi: 10.1002/j.1460-2075.1995.tb07201.x.
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A direct effect of activated human p53 on nuclear DNA replication.
Cox LS
,
Hupp T
,
Midgley CA
,
Lane DP
.
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p53 is a transcriptional activator and repressor, but recent evidence suggests that some of its many biological functions may not be dependent on transcription. To determine whether p53 exerts a direct influence on nuclear DNA replication, purified human p53 was added to a transcription-free DNA replication extract from Xenopus eggs. Full-length human p53 that inhibits SV40 DNA replication in vitro had no effect on nuclear DNA synthesis in the Xenopus system. In contrast, a C-terminal truncated form of p53 (p53 delta 30), which is constitutively active for DNA binding and similar to an alternately spliced form found in vivo, showed a concentration-dependent inhibition of DNA replication in both the soluble SV40 system and eukaryotic nuclei. This inhibition occurred primarily at initiation of DNA synthesis. Oxidation of p53 delta 30, which eliminates DNA binding activity, also abrogated the protein's ability to inhibit nuclear DNA synthesis. The p53 binding DNA consensus sequence enhanced rather than competed away inhibitory activity of p53 delta 30. Therefore, p53 that is constitutively active for DNA binding can inhibit nuclear DNA replication in the absence of transcription. This inhibition may require binding of p53 to DNA, in addition to interactions between p53 and proteins of the replication complex.
Arai,
Immunologically distinct p53 molecules generated by alternative splicing.
1986, Pubmed
Arai,
Immunologically distinct p53 molecules generated by alternative splicing.
1986,
Pubmed
Blow,
Initiation of DNA replication in nuclei and purified DNA by a cell-free extract of Xenopus eggs.
1986,
Pubmed
,
Xenbase
Blow,
Nuclei act as independent and integrated units of replication in a Xenopus cell-free DNA replication system.
1987,
Pubmed
,
Xenbase
Blow,
A role for the nuclear envelope in controlling DNA replication within the cell cycle.
1988,
Pubmed
,
Xenbase
Brain,
Human p53 directs DNA strand reassociation and is photolabelled by 8-azido ATP.
1994,
Pubmed
Braithwaite,
Mouse p53 inhibits SV40 origin-dependent DNA replication.
,
Pubmed
Caelles,
p53-dependent apoptosis in the absence of transcriptional activation of p53-target genes.
1994,
Pubmed
Cho,
Crystal structure of a p53 tumor suppressor-DNA complex: understanding tumorigenic mutations.
1994,
Pubmed
Clore,
High-resolution structure of the oligomerization domain of p53 by multidimensional NMR.
1994,
Pubmed
Cox,
Extracts from eggs and oocytes of Xenopus laevis differ in their capacities for nuclear assembly and DNA replication.
1990,
Pubmed
,
Xenbase
Cox,
DNA replication occurs at discrete sites in pseudonuclei assembled from purified DNA in vitro.
1991,
Pubmed
,
Xenbase
Cox,
Xenopus p53 is biochemically similar to the human tumour suppressor protein p53 and is induced upon DNA damage in somatic cells.
1994,
Pubmed
,
Xenbase
Crook,
Transcriptional activation by p53 correlates with suppression of growth but not transformation.
1994,
Pubmed
Dulić,
p53-dependent inhibition of cyclin-dependent kinase activities in human fibroblasts during radiation-induced G1 arrest.
1994,
Pubmed
Dutta,
Inhibition of DNA replication factor RPA by p53.
1993,
Pubmed
Fields,
Presence of a potent transcription activating sequence in the p53 protein.
1990,
Pubmed
Flores-Rozas,
Cdk-interacting protein 1 directly binds with proliferating cell nuclear antigen and inhibits DNA replication catalyzed by the DNA polymerase delta holoenzyme.
1994,
Pubmed
Friedman,
Wild-type, but not mutant, human p53 proteins inhibit the replication activities of simian virus 40 large tumor antigen.
1990,
Pubmed
Friend,
p53: a glimpse at the puppet behind the shadow play.
1994,
Pubmed
Gannon,
p53 and DNA polymerase alpha compete for binding to SV40 T antigen.
,
Pubmed
Gu,
Inhibition of CDK2 activity in vivo by an associated 20K regulatory subunit.
1993,
Pubmed
Gurdon,
Injected nuclei in frog oocytes: fate, enlargement, and chromatin dispersal.
1976,
Pubmed
,
Xenbase
Halazonetis,
Wild-type p53 adopts a 'mutant'-like conformation when bound to DNA.
1993,
Pubmed
Han,
Alternatively spliced p53 RNA in transformed and normal cells of different tissue types.
1992,
Pubmed
Harper,
The p21 Cdk-interacting protein Cip1 is a potent inhibitor of G1 cyclin-dependent kinases.
1993,
Pubmed
He,
The transactivator proteins VP16 and GAL4 bind replication factor A.
1993,
Pubmed
Hoever,
Overexpression of wild-type p53 interferes with normal development in Xenopus laevis embryos.
1994,
Pubmed
,
Xenbase
Hollstein,
p53 mutations in human cancers.
1991,
Pubmed
,
Xenbase
Hupp,
Activation of the cryptic DNA binding function of mutant forms of p53.
1993,
Pubmed
Hupp,
Regulation of the specific DNA binding function of p53.
1992,
Pubmed
Hutchison,
Periodic DNA synthesis in cell-free extracts of Xenopus eggs.
1987,
Pubmed
,
Xenbase
Hutchison,
Changes in the nuclear distribution of DNA polymerase alpha and PCNA/cyclin during the progress of the cell cycle, in a cell-free extract of Xenopus eggs.
1989,
Pubmed
,
Xenbase
Iwabuchi,
Two cellular proteins that bind to wild-type but not mutant p53.
1994,
Pubmed
Kastan,
A mammalian cell cycle checkpoint pathway utilizing p53 and GADD45 is defective in ataxia-telangiectasia.
1992,
Pubmed
Kulesz-Martin,
Endogenous p53 protein generated from wild-type alternatively spliced p53 RNA in mouse epidermal cells.
1994,
Pubmed
Lane,
Cancer. p53, guardian of the genome.
1992,
Pubmed
Lane,
T antigen is bound to a host protein in SV40-transformed cells.
1979,
Pubmed
Laskey,
Chromosome replication in early development of Xenopus laevis.
1985,
Pubmed
,
Xenbase
Li,
The acidic transcriptional activation domains of VP16 and p53 bind the cellular replication protein A and stimulate in vitro BPV-1 DNA replication.
1993,
Pubmed
Linzer,
Characterization of a 54K dalton cellular SV40 tumor antigen present in SV40-transformed cells and uninfected embryonal carcinoma cells.
1979,
Pubmed
Lu,
Differential induction of transcriptionally active p53 following UV or ionizing radiation: defects in chromosome instability syndromes?
1993,
Pubmed
Maxwell,
Binding of cellular proteins to a conformational domain of tumor suppressor protein p53.
1993,
Pubmed
Meek,
The p53 tumour suppressor protein is phosphorylated at serine 389 by casein kinase II.
1990,
Pubmed
Midgley,
Analysis of p53 expression in human tumours: an antibody raised against human p53 expressed in Escherichia coli.
1992,
Pubmed
Mills,
Replication occurs at discrete foci spaced throughout nuclei replicating in vitro.
1989,
Pubmed
,
Xenbase
Milner,
Partially transformed T3T3 cells express high levels of mutant p53 in the 'wild-type' immunoreactive form with defective oligomerization.
1993,
Pubmed
Mulligan,
Mechanisms of p53 loss in human sarcomas.
1990,
Pubmed
Méchali,
DNA synthesis in a cell-free system from Xenopus eggs: priming and elongation on single-stranded DNA in vitro.
1982,
Pubmed
,
Xenbase
Newport,
A major developmental transition in early Xenopus embryos: I. characterization and timing of cellular changes at the midblastula stage.
1982,
Pubmed
,
Xenbase
Nigro,
Mutations in the p53 gene occur in diverse human tumour types.
1989,
Pubmed
Oberosler,
p53-catalyzed annealing of complementary single-stranded nucleic acids.
1993,
Pubmed
Pietenpol,
Tumour suppressor genes. No room at the p53 inn.
1993,
Pubmed
Pietenpol,
Sequence-specific transcriptional activation is essential for growth suppression by p53.
1994,
Pubmed
Reed,
p53 domains: suppression, transformation, and transactivation.
1993,
Pubmed
Sang,
Distinct regions of p53 have a differential role in transcriptional activation and repression functions.
1994,
Pubmed
Serrano,
A new regulatory motif in cell-cycle control causing specific inhibition of cyclin D/CDK4.
1993,
Pubmed
Soussi,
Cloning and characterization of a cDNA from Xenopus laevis coding for a protein homologous to human and murine p53.
1987,
Pubmed
,
Xenbase
Stürzbecher,
Mouse p53 blocks SV40 DNA replication in vitro and downregulates T antigen DNA helicase activity.
1988,
Pubmed
Subler,
Overlapping domains on the p53 protein regulate its transcriptional activation and repression functions.
1994,
Pubmed
Takimoto,
Identification of cellular proteins that bind the central conserved region of p53.
1994,
Pubmed
Tchang,
Stabilization and expression of high levels of p53 during early development in Xenopus laevis.
1993,
Pubmed
,
Xenbase
Vojtĕsek,
An immunochemical analysis of the human nuclear phosphoprotein p53. New monoclonal antibodies and epitope mapping using recombinant p53.
1992,
Pubmed
Waga,
The p21 inhibitor of cyclin-dependent kinases controls DNA replication by interaction with PCNA.
1994,
Pubmed
Wang,
The murine p53 protein blocks replication of SV40 DNA in vitro by inhibiting the initiation functions of SV40 large T antigen.
1989,
Pubmed
Warbrick,
A small peptide inhibitor of DNA replication defines the site of interaction between the cyclin-dependent kinase inhibitor p21WAF1 and proliferating cell nuclear antigen.
1995,
Pubmed
Xiong,
p21 is a universal inhibitor of cyclin kinases.
1993,
Pubmed
Zhang,
Novel DNA binding of p53 mutants and their role in transcriptional activation.
1993,
Pubmed
Zhang,
Inactive p53 mutants may enhance the transcriptional activity of wild-type p53.
1993,
Pubmed
Zhang,
A temperature-sensitive mutant of human p53.
1994,
Pubmed
el-Deiry,
WAF1, a potential mediator of p53 tumor suppression.
1993,
Pubmed
el-Deiry,
Definition of a consensus binding site for p53.
1992,
Pubmed