Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
EMBO J
1998 Mar 16;176:1810-8. doi: 10.1093/emboj/17.6.1810.
Show Gene links
Show Anatomy links
Transformation abrogates an early G1-phase arrest point required for specification of the Chinese hamster DHFR replication origin.
Wu JR
,
Keezer SM
,
Gilbert DM
.
???displayArticle.abstract???
The origin decision point (ODP) was originally identified as a distinct point during G1-phase when Chinese hamster ovary (CHO) cell nuclei experience a transition that is required for specific recognition of the dihydrofolate reductase (DHFR) origin locus by Xenopus egg extracts. Passage of cells through the ODP requires a mitogen-independent protein kinase that is activated prior to restriction point control. Here we show that inhibition of an early G1-phase protein kinase pathway by the addition of 2-aminopurine (2-AP) prior to the ODP arrests CHO cells in G1-phase. Transformation with simian virus 40 (SV40) abrogated this arrest point, resulting in the entry of cultured cells into S-phase in the presence of 2-AP and a disruption of the normal pattern of initiation sites at the DHFR locus. Cells treated with 2-AP after the ODP initiated replication specifically within the DHFR origin locus. Transient exposure of transformed cells to 2-AP during the ODP transition also disrupted origin choice, whereas non-transformed cells arrested in G1-phase and then passed through a delayed ODP after removal of 2-AP from the medium. We conclude that mammalian cells have many potential sites at which they can initiate replication. Normally, events occurring during the early G1-phase ODP transition determine which of these sites will be the preferred initiation site. However, if chromatin is exposed to S-phase-promoting factors prior to this transition, mammalian cells, like Xenopus and Drosophila embryos, can initiate replication without origin specification.
Anderson,
Metabolism of Okazaki fragments during simian virus 40 DNA replication.
1979, Pubmed
Anderson,
Metabolism of Okazaki fragments during simian virus 40 DNA replication.
1979,
Pubmed
Burhans,
Identification of an origin of bidirectional DNA replication in mammalian chromosomes.
1990,
Pubmed
Burhans,
Emetine allows identification of origins of mammalian DNA replication by imbalanced DNA synthesis, not through conservative nucleosome segregation.
1991,
Pubmed
Coverley,
Regulation of eukaryotic DNA replication.
1994,
Pubmed
Crissman,
Transformed mammalian cells are deficient in kinase-mediated control of progression through the G1 phase of the cell cycle.
1991,
Pubmed
DePamphilis,
Origins of DNA replication in metazoan chromosomes.
1993,
Pubmed
Dijkwel,
The Chinese hamster dihydrofolate reductase origin consists of multiple potential nascent-strand start sites.
1995,
Pubmed
Distel,
A unified nomenclature for peroxisome biogenesis factors.
1996,
Pubmed
Gadbois,
Multiple kinase arrest points in the G1 phase of nontransformed mammalian cells are absent in transformed cells.
1992,
Pubmed
Gilbert,
Site-specific initiation of DNA replication in Xenopus egg extract requires nuclear structure.
1995,
Pubmed
,
Xenbase
Gilbert,
Bovine papilloma virus plasmids replicate randomly in mouse fibroblasts throughout S phase of the cell cycle.
1987,
Pubmed
Gilbert,
Position effects on the timing of replication of chromosomally integrated simian virus 40 molecules in Chinese hamster cells.
1990,
Pubmed
Gruss,
Disruption of the nucleosomes at the replication fork.
1993,
Pubmed
,
Xenbase
Hamlin,
Defining origins of replication in mammalian cells.
1994,
Pubmed
Hamlin,
On the nature of replication origins in higher eukaryotes.
1995,
Pubmed
Hyrien,
Chromosomal replication initiates and terminates at random sequences but at regular intervals in the ribosomal DNA of Xenopus early embryos.
1993,
Pubmed
,
Xenbase
Hyrien,
Transition in specification of embryonic metazoan DNA replication origins.
1995,
Pubmed
,
Xenbase
Joo,
Purification of the simian virus 40 (SV40) T antigen DNA-binding domain and characterization of its interactions with the SV40 origin.
1997,
Pubmed
Leno,
The nuclear membrane prevents replication of human G2 nuclei but not G1 nuclei in Xenopus egg extract.
1992,
Pubmed
,
Xenbase
Little,
Initiation of latent DNA replication in the Epstein-Barr virus genome can occur at sites other than the genetically defined origin.
1995,
Pubmed
Little,
Initiation and termination of DNA replication in human rRNA genes.
1993,
Pubmed
Ludlow,
SV40 large T antigen binds preferentially to an underphosphorylated member of the retinoblastoma susceptibility gene product family.
1989,
Pubmed
O'Keefe,
Dynamic organization of DNA replication in mammalian cell nuclei: spatially and temporally defined replication of chromosome-specific alpha-satellite DNA sequences.
1992,
Pubmed
Pelizon,
High-resolution mapping of the origin of DNA replication in the hamster dihydrofolate reductase gene domain by competitive PCR.
1996,
Pubmed
Shinomiya,
DNA replication of histone gene repeats in Drosophila melanogaster tissue culture cells: multiple initiation sites and replication pause sites.
1993,
Pubmed
Shinomiya,
Mapping an initiation region of DNA replication at a single-copy chromosomal locus in Drosophila melanogaster cells by two-dimensional gel methods and PCR-mediated nascent-strand analysis: multiple replication origins in a broad zone.
1994,
Pubmed
Wu,
A distinct G1 step required to specify the Chinese hamster DHFR replication origin.
1996,
Pubmed
,
Xenbase
Wu,
The replication origin decision point is a mitogen-independent, 2-aminopurine-sensitive, G1-phase event that precedes restriction point control.
1997,
Pubmed
,
Xenbase
Wu,
Origin-specific initiation of mammalian nuclear DNA replication in a Xenopus cell-free system.
1997,
Pubmed
,
Xenbase
Zetterberg,
What is the restriction point?
1995,
Pubmed
