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Mol Cell Biol
2000 Nov 01;2022:8602-12. doi: 10.1128/MCB.20.22.8602-8612.2000.
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Chromatin association of human origin recognition complex, cdc6, and minichromosome maintenance proteins during the cell cycle: assembly of prereplication complexes in late mitosis.
Méndez J
,
Stillman B
.
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Evidence obtained from studies with yeast and Xenopus indicate that the initiation of DNA replication is a multistep process. The origin recognition complex (ORC), Cdc6p, and minichromosome maintenance (MCM) proteins are required for establishing prereplication complexes, upon which initiation is triggered by the activation of cyclin-dependent kinases and the Dbf4p-dependent kinase Cdc7p. The identification of human homologues of these replication proteins allows investigation of S-phase regulation in mammalian cells. Using centrifugal elutriation of several human cell lines, we demonstrate that whereas human Orc2 (hOrc2p) and hMcm proteins are present throughout the cell cycle, hCdc6p levels vary, being very low in early G(1) and accumulating until cells enter mitosis. hCdc6p can be polyubiquitinated in vivo, and it is stabilized by proteasome inhibitors. Similar to the case for hOrc2p, a significant fraction of hCdc6p is present on chromatin throughout the cell cycle, whereas hMcm proteins alternate between soluble and chromatin-bound forms. Loading of hMcm proteins onto chromatin occurs in late mitosis concomitant with the destruction of cyclin B, indicating that the mitotic kinase activity inhibits prereplication complex formation in human cells.
Aparicio,
Components and dynamics of DNA replication complexes in S. cerevisiae: redistribution of MCM proteins and Cdc45p during S phase.
1997, Pubmed
Aparicio,
Components and dynamics of DNA replication complexes in S. cerevisiae: redistribution of MCM proteins and Cdc45p during S phase.
1997,
Pubmed
Bell,
ATP-dependent recognition of eukaryotic origins of DNA replication by a multiprotein complex.
1992,
Pubmed
Bolt,
High-efficiency blotting of proteins of diverse sizes following sodium dodecyl sulfate-polyacrylamide gel electrophoresis.
1997,
Pubmed
Bueno,
Dual functions of CDC6: a yeast protein required for DNA replication also inhibits nuclear division.
1992,
Pubmed
Chong,
A double-hexamer archaeal minichromosome maintenance protein is an ATP-dependent DNA helicase.
2000,
Pubmed
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,
Protein kinase inhibition in G2 causes mammalian Mcm proteins to reassociate with chromatin and restores ability to replicate.
1998,
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
Dahmann,
S-phase-promoting cyclin-dependent kinases prevent re-replication by inhibiting the transition of replication origins to a pre-replicative state.
1995,
Pubmed
Diffley,
Two steps in the assembly of complexes at yeast replication origins in vivo.
1994,
Pubmed
,
Xenbase
Dimitrova,
Mcm2, but not RPA, is a component of the mammalian early G1-phase prereplication complex.
1999,
Pubmed
,
Xenbase
Donovan,
Cdc6p-dependent loading of Mcm proteins onto pre-replicative chromatin in budding yeast.
1997,
Pubmed
,
Xenbase
Drury,
The Cdc4/34/53 pathway targets Cdc6p for proteolysis in budding yeast.
1997,
Pubmed
Drury,
The cyclin-dependent kinase Cdc28p regulates distinct modes of Cdc6p proteolysis during the budding yeast cell cycle.
2000,
Pubmed
Dutta,
Initiation of DNA replication in eukaryotic cells.
1997,
Pubmed
Fujita,
Cell cycle regulation of human CDC6 protein. Intracellular localization, interaction with the human mcm complex, and CDC2 kinase-mediated hyperphosphorylation.
1999,
Pubmed
Fujita,
hCDC47, a human member of the MCM family. Dissociation of the nucleus-bound form during S phase.
1996,
Pubmed
Gavin,
Conserved initiator proteins in eukaryotes.
1995,
Pubmed
Herbig,
The Cdc6 nucleotide-binding site regulates its activity in DNA replication in human cells.
1999,
Pubmed
Holthoff,
Human protein MCM6 on HeLa cell chromatin.
1998,
Pubmed
Ishimi,
A DNA helicase activity is associated with an MCM4, -6, and -7 protein complex.
1997,
Pubmed
Jallepalli,
Cyclin-dependent kinase and initiation at eukaryotic origins: a replication switch?
1997,
Pubmed
Jallepalli,
Regulation of the replication initiator protein p65cdc18 by CDK phosphorylation.
1997,
Pubmed
Jallepalli,
Rum1 and Cdc18 link inhibition of cyclin-dependent kinase to the initiation of DNA replication in Schizosaccharomyces pombe.
1996,
Pubmed
Jiang,
Multistep regulation of DNA replication by Cdk phosphorylation of HsCdc6.
1999,
Pubmed
Kearsey,
MCM proteins: evolution, properties, and role in DNA replication.
1998,
Pubmed
Kelly,
The fission yeast cdc18+ gene product couples S phase to START and mitosis.
1993,
Pubmed
Kelman,
The single minichromosome maintenance protein of Methanobacterium thermoautotrophicum DeltaH contains DNA helicase activity.
1999,
Pubmed
Krek,
Cell synchronization.
1995,
Pubmed
Krude,
Human replication proteins hCdc21, hCdc46 and P1Mcm3 bind chromatin uniformly before S-phase and are displaced locally during DNA replication.
1996,
Pubmed
,
Xenbase
Labib,
Uninterrupted MCM2-7 function required for DNA replication fork progression.
2000,
Pubmed
Liang,
ORC and Cdc6p interact and determine the frequency of initiation of DNA replication in the genome.
1995,
Pubmed
Liang,
Persistent initiation of DNA replication and chromatin-bound MCM proteins during the cell cycle in cdc6 mutants.
1997,
Pubmed
Madine,
The roles of the MCM, ORC, and Cdc6 proteins in determining the replication competence of chromatin in quiescent cells.
2000,
Pubmed
,
Xenbase
Maiorano,
Stepwise regulated chromatin assembly of MCM2-7 proteins.
2000,
Pubmed
,
Xenbase
Maiorano,
XCDT1 is required for the assembly of pre-replicative complexes in Xenopus laevis.
2000,
Pubmed
,
Xenbase
McGarry,
Geminin, an inhibitor of DNA replication, is degraded during mitosis.
1998,
Pubmed
,
Xenbase
Mizushima,
Cdc6p modulates the structure and DNA binding activity of the origin recognition complex in vitro.
2000,
Pubmed
Muzi Falconi,
cdc18+ regulates initiation of DNA replication in Schizosaccharomyces pombe.
1996,
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
Neuwald,
AAA+: A class of chaperone-like ATPases associated with the assembly, operation, and disassembly of protein complexes.
1999,
Pubmed
Nishitani,
The Cdt1 protein is required to license DNA for replication in fission yeast.
2000,
Pubmed
Nishitani,
p65cdc18 plays a major role controlling the initiation of DNA replication in fission yeast.
1995,
Pubmed
Perkins,
Nucleotide-dependent prereplicative complex assembly by Cdc6p, a homolog of eukaryotic and prokaryotic clamp-loaders.
1998,
Pubmed
Petersen,
Phosphorylation of mammalian CDC6 by cyclin A/CDK2 regulates its subcellular localization.
1999,
Pubmed
Piatti,
Cdc6 is an unstable protein whose de novo synthesis in G1 is important for the onset of S phase and for preventing a 'reductional' anaphase in the budding yeast Saccharomyces cerevisiae.
1995,
Pubmed
Piatti,
Activation of S-phase-promoting CDKs in late G1 defines a "point of no return" after which Cdc6 synthesis cannot promote DNA replication in yeast.
1996,
Pubmed
Quintana,
Identification of HsORC4, a member of the human origin of replication recognition complex.
1997,
Pubmed
Quintana,
ORC5L, a new member of the human origin recognition complex, is deleted in uterine leiomyomas and malignant myeloid diseases.
1998,
Pubmed
Ritzi,
Human minichromosome maintenance proteins and human origin recognition complex 2 protein on chromatin.
1998,
Pubmed
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
Salghetti,
Destruction of Myc by ubiquitin-mediated proteolysis: cancer-associated and transforming mutations stabilize Myc.
1999,
Pubmed
Sánchez,
The Cdc6 protein is ubiquitinated in vivo for proteolysis in Saccharomyces cerevisiae.
1999,
Pubmed
Schulte,
Expression, phosphorylation and nuclear localization of the human P1 protein, a homologue of the yeast Mcm 3 replication protein.
1995,
Pubmed
Schulte,
Properties of the human nuclear protein p85Mcm. Expression, nuclear localization and interaction with other Mcm proteins.
1996,
Pubmed
Stillman,
Cell cycle control of DNA replication.
1996,
Pubmed
Stoeber,
Cdc6 protein causes premature entry into S phase in a mammalian cell-free system.
1998,
Pubmed
Tanaka,
Loading of an Mcm protein onto DNA replication origins is regulated by Cdc6p and CDKs.
1997,
Pubmed
Todorov,
BM28, a human member of the MCM2-3-5 family, is displaced from chromatin during DNA replication.
1995,
Pubmed
Treier,
Ubiquitin-dependent c-Jun degradation in vivo is mediated by the delta domain.
1994,
Pubmed
Tugal,
The Orc4p and Orc5p subunits of the Xenopus and human origin recognition complex are related to Orc1p and Cdc6p.
1998,
Pubmed
,
Xenbase
Weinreich,
The Cdc6p nucleotide-binding motif is required for loading mcm proteins onto chromatin.
1999,
Pubmed
Williams,
Improved cervical smear assessment using antibodies against proteins that regulate DNA replication.
1998,
Pubmed
Williams,
A human protein related to yeast Cdc6p.
1997,
Pubmed
,
Xenbase
Wu,
A distinct G1 step required to specify the Chinese hamster DHFR replication origin.
1996,
Pubmed
,
Xenbase
Yan,
PR48, a novel regulatory subunit of protein phosphatase 2A, interacts with Cdc6 and modulates DNA replication in human cells.
2000,
Pubmed
Yan,
Cdc6 is regulated by E2F and is essential for DNA replication in mammalian cells.
1998,
Pubmed
Zou,
Assembly of a complex containing Cdc45p, replication protein A, and Mcm2p at replication origins controlled by S-phase cyclin-dependent kinases and Cdc7p-Dbf4p kinase.
2000,
Pubmed
