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.
???displayArticle.abstract???
Previous studies have suggested that cell cycle-dependent changes in the affinity of the origin recognition complex (ORC) for chromatin are involved in regulating initiation of DNA replication. To test this hypothesis, chromatin lacking functional ORCs was isolated from metaphase hamster cells and incubated in Xenopus egg extracts to initiate DNA replication. Intriguingly, Xenopus ORC rapidly bound to hamster somatic chromatin in a Cdc6-dependent manner and was then released, concomitant with initiation of DNA replication. Once pre-replication complexes (pre-RCs) were assembled either in vitro or in vivo, further binding of XlORC was inhibited. Neither binding nor release of XlORC was affected by inhibitors of either cyclin-dependent protein kinase activity or DNA synthesis. In contrast, inhibition of pre-RC assembly, either by addition of Xenopus geminin or by depletion of XlMcm proteins, augmented ORC binding by inhibiting ORC release. These results demonstrate a programmed release of XlORC from somatic cell chromatin as it enters S phase, consistent with the proposed role for ORC in preventing re-initiation of DNA replication during S phase.
Abdurashidova,
Cell cycle modulation of protein-DNA interactions at a human replication origin.
1998, Pubmed,
Xenbase
Abdurashidova,
Cell cycle modulation of protein-DNA interactions at a human replication origin.
1998,
Pubmed
,
Xenbase
Altman,
The Chinese hamster dihydrofolate reductase replication origin beta is active at multiple ectopic chromosomal locations and requires specific DNA sequence elements for activity.
2001,
Pubmed
Asano,
E2F mediates developmental and cell cycle regulation of ORC1 in Drosophila.
1999,
Pubmed
Blow,
Control of chromosomal DNA replication in the early Xenopus embryo.
2001,
Pubmed
,
Xenbase
Bogan,
Initiation of eukaryotic DNA replication: conservative or liberal?
2000,
Pubmed
Carpenter,
Role for a Xenopus Orc2-related protein in controlling DNA replication.
1996,
Pubmed
,
Xenbase
Chong,
Characterization of the Xenopus replication licensing system.
1997,
Pubmed
,
Xenbase
Coleman,
The Xenopus Cdc6 protein is essential for the initiation of a single round of DNA replication in cell-free extracts.
1996,
Pubmed
,
Xenbase
Coverley,
Chromatin-bound Cdc6 persists in S and G2 phases in human cells, while soluble Cdc6 is destroyed in a cyclin A-cdk2 dependent process.
2000,
Pubmed
,
Xenbase
Decker,
In vitro initiation of DNA replication in simian virus 40 chromosomes.
1987,
Pubmed
DePamphilis,
Replication origins in metazoan chromosomes: fact or fiction?
1999,
Pubmed
Dhar,
Architecture of the human origin recognition complex.
2001,
Pubmed
Dhar,
Replication from oriP of Epstein-Barr virus requires human ORC and is inhibited by geminin.
2001,
Pubmed
Dimitrov,
Remodeling sperm chromatin in Xenopus laevis egg extracts: the role of core histone phosphorylation and linker histone B4 in chromatin assembly.
1994,
Pubmed
,
Xenbase
Donovan,
Cdc6p-dependent loading of Mcm proteins onto pre-replicative chromatin in budding yeast.
1997,
Pubmed
,
Xenbase
Drury,
The cyclin-dependent kinase Cdc28p regulates distinct modes of Cdc6p proteolysis during the budding yeast cell cycle.
2000,
Pubmed
Findeisen,
Cyclin A-dependent kinase activity affects chromatin binding of ORC, Cdc6, and MCM in egg extracts of Xenopus laevis.
1999,
Pubmed
,
Xenbase
Gilbert,
Mimosine arrests DNA synthesis at replication forks by inhibiting deoxyribonucleotide metabolism.
1995,
Pubmed
,
Xenbase
Gilbert,
Site-specific initiation of DNA replication in Xenopus egg extract requires nuclear structure.
1995,
Pubmed
,
Xenbase
Gillespie,
Nucleoplasmin-mediated chromatin remodelling is required for Xenopus sperm nuclei to become licensed for DNA replication.
2000,
Pubmed
,
Xenbase
Hua,
Identification of a preinitiation step in DNA replication that is independent of origin recognition complex and cdc6, but dependent on cdk2.
1998,
Pubmed
,
Xenbase
Jares,
Xenopus cdc7 function is dependent on licensing but not on XORC, XCdc6, or CDK activity and is required for XCdc45 loading.
2000,
Pubmed
,
Xenbase
Jiang,
Multistep regulation of DNA replication by Cdk phosphorylation of HsCdc6.
1999,
Pubmed
Kelly,
Regulation of chromosome replication.
2000,
Pubmed
Kong,
Site-specific DNA binding of the Schizosaccharomyces pombe origin recognition complex is determined by the Orc4 subunit.
2001,
Pubmed
Kreitz,
The human origin recognition complex protein 1 dissociates from chromatin during S phase in HeLa cells.
2001,
Pubmed
,
Xenbase
Landsman,
Histone H1 in Saccharomyces cerevisiae: a double mystery solved?
1996,
Pubmed
Li,
Mammalian Orc1 protein is selectively released from chromatin and ubiquitinated during the S-to-M transition in the cell division cycle.
2002,
Pubmed
Li,
Selective activation of pre-replication complexes in vitro at specific sites in mammalian nuclei.
2000,
Pubmed
,
Xenbase
Lygerou,
The fission yeast origin recognition complex is constitutively associated with chromatin and is differentially modified through the cell cycle.
1999,
Pubmed
McGarry,
Geminin, an inhibitor of DNA replication, is degraded during mitosis.
1998,
Pubmed
,
Xenbase
Méndez,
Chromatin association of human origin recognition complex, cdc6, and minichromosome maintenance proteins during the cell cycle: assembly of prereplication complexes in late mitosis.
2000,
Pubmed
,
Xenbase
Mizushima,
Cdc6p modulates the structure and DNA binding activity of the origin recognition complex in vitro.
2000,
Pubmed
Natale,
Selective instability of Orc1 protein accounts for the absence of functional origin recognition complexes during the M-G(1) transition in mammals.
2000,
Pubmed
,
Xenbase
Nethanel,
Two DNA polymerases may be required for synthesis of the lagging DNA strand of simian virus 40.
1990,
Pubmed
Nguyen,
Cyclin-dependent kinases prevent DNA re-replication through multiple mechanisms.
2001,
Pubmed
Okuno,
Stability, chromatin association and functional activity of mammalian pre-replication complex proteins during the cell cycle.
2001,
Pubmed
,
Xenbase
Pak,
Association of the origin recognition complex with heterochromatin and HP1 in higher eukaryotes.
1997,
Pubmed
,
Xenbase
Pelizon,
Unphosphorylatable mutants of Cdc6 disrupt its nuclear export but still support DNA replication once per cell cycle.
2000,
Pubmed
,
Xenbase
Petersen,
Cell cycle- and cell growth-regulated proteolysis of mammalian CDC6 is dependent on APC-CDH1.
2000,
Pubmed
Petersen,
Phosphorylation of mammalian CDC6 by cyclin A/CDK2 regulates its subcellular localization.
1999,
Pubmed
Philpott,
Nucleoplasmin remodels sperm chromatin in Xenopus egg extracts.
1992,
Pubmed
,
Xenbase
Ritzi,
Human minichromosome maintenance proteins and human origin recognition complex 2 protein on chromatin.
1998,
Pubmed
Romanowski,
The Xenopus origin recognition complex is essential for DNA replication and MCM binding to chromatin.
1996,
Pubmed
,
Xenbase
Rowles,
Interaction between the origin recognition complex and the replication licensing system in Xenopus.
1996,
Pubmed
,
Xenbase
Rowles,
Changes in association of the Xenopus origin recognition complex with chromatin on licensing of replication origins.
1999,
Pubmed
,
Xenbase
Saha,
Human CDC6/Cdc18 associates with Orc1 and cyclin-cdk and is selectively eliminated from the nucleus at the onset of S phase.
1998,
Pubmed
Smythe,
Systems for the study of nuclear assembly, DNA replication, and nuclear breakdown in Xenopus laevis egg extracts.
1991,
Pubmed
,
Xenbase
Sun,
The replication capacity of intact mammalian nuclei in Xenopus egg extracts declines with quiescence, but the residual DNA synthesis is independent of Xenopus MCM proteins.
2000,
Pubmed
,
Xenbase
Tada,
Repression of origin assembly in metaphase depends on inhibition of RLF-B/Cdt1 by geminin.
2001,
Pubmed
,
Xenbase
Thömmes,
The RLF-M component of the replication licensing system forms complexes containing all six MCM/P1 polypeptides.
1997,
Pubmed
,
Xenbase
Tugal,
The Orc4p and Orc5p subunits of the Xenopus and human origin recognition complex are related to Orc1p and Cdc6p.
1998,
Pubmed
,
Xenbase
Vashee,
Assembly of the human origin recognition complex.
2001,
Pubmed
Walter,
Evidence for sequential action of cdc7 and cdk2 protein kinases during initiation of DNA replication in Xenopus egg extracts.
2000,
Pubmed
,
Xenbase
Wang,
The essential role of Saccharomyces cerevisiae CDC6 nucleotide-binding site in cell growth, DNA synthesis, and Orc1 association.
1999,
Pubmed
Wohlschlegel,
Inhibition of eukaryotic DNA replication by geminin binding to Cdt1.
2000,
Pubmed
,
Xenbase
Wu,
Transformation abrogates an early G1-phase arrest point required for specification of the Chinese hamster DHFR replication origin.
1998,
Pubmed
,
Xenbase
Wu,
Origin-specific initiation of mammalian nuclear DNA replication in a Xenopus cell-free system.
1997,
Pubmed
,
Xenbase
Wu,
A distinct G1 step required to specify the Chinese hamster DHFR replication origin.
1996,
Pubmed
,
Xenbase
Yu,
Analysis of mammalian origin specification in ORC-depleted Xenopus egg extracts.
1998,
Pubmed
,
Xenbase
