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.
Proc Natl Acad Sci U S A
1997 May 27;9411:5611-6. doi: 10.1073/pnas.94.11.5611.
Show Gene links
Show Anatomy links
Cdc6p-dependent loading of Mcm proteins onto pre-replicative chromatin in budding yeast.
Donovan S
,
Harwood J
,
Drury LS
,
Diffley JF
.
???displayArticle.abstract???
The Cdc6 protein is essential for the assembly of pre-replicative complexes (pre-RCs) at origins of DNA replication in the budding yeast Saccharomyces cerevisiae. This reaction is blocked in vivo by the cyclin-dependent kinase Cdc28p, together with its regulatory subunits, the B type cyclins that are present throughout S, G2, and M phases. Because the destruction of B type cyclins and the consequent inactivation of the kinase are essential for exit from mitosis, pre-RC formation can only occur after passage through mitosis. Therefore, pre-RC formation has been proposed to be essential for coupling S phase and mitosis and for limiting DNA replication to once per cell cycle. The Mcm2-7 family of proteins has been implicated in limiting replication to once per cell cycle from experiments with Xenopus egg extracts. Here we show that the Mcm proteins of budding yeast are abundant and are quantitatively found in a chromatin-enriched fraction specifically during the G1 phase of the cell cycle. This chromatin binding depends on the de novo synthesis of Cdc6p, providing evidence that a conserved biochemical pathway plays a critical role in coordinating DNA replication with mitosis in both yeast and higher eukaryotes. Cdc6p and the origin recognition complex can be selectively removed from this chromatin-enriched fraction without removing the Mcm proteins. From these results, we propose that Cdc6p (and the origin recognition complex) nucleates the binding of Mcm proteins to chromatin, but once bound, the Mcm proteins appear to interact tightly with some other component of chromatin.
Bell,
ATP-dependent recognition of eukaryotic origins of DNA replication by a multiprotein complex.
1992, Pubmed
Bell,
ATP-dependent recognition of eukaryotic origins of DNA replication by a multiprotein complex.
1992,
Pubmed
Blow,
Preventing re-replication of DNA in a single cell cycle: evidence for a replication licensing factor.
1993,
Pubmed
,
Xenbase
Blow,
A role for the nuclear envelope in controlling DNA replication within the cell cycle.
1988,
Pubmed
,
Xenbase
Broek,
Involvement of p34cdc2 in establishing the dependency of S phase on mitosis.
1991,
Pubmed
Carpenter,
Role for a Xenopus Orc2-related protein in controlling DNA replication.
1996,
Pubmed
,
Xenbase
Chong,
Purification of an MCM-containing complex as a component of the DNA replication licensing system.
1995,
Pubmed
,
Xenbase
Chong,
The role of MCM/P1 proteins in the licensing of DNA replication.
1996,
Pubmed
Cocker,
An essential role for the Cdc6 protein in forming the pre-replicative complexes of budding yeast.
1996,
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
Conradt,
In vitro reactions of vacuole inheritance in Saccharomyces cerevisiae.
1992,
Pubmed
Coxon,
Fission yeast cdc21+ belongs to a family of proteins involved in an early step of chromosome replication.
1992,
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
Dalton,
Cell cycle-regulated nuclear import and export of Cdc47, a protein essential for initiation of DNA replication in budding yeast.
1995,
Pubmed
Diffley,
Protein-DNA interactions at a yeast replication origin.
1992,
Pubmed
Diffley,
Two steps in the assembly of complexes at yeast replication origins in vivo.
1994,
Pubmed
,
Xenbase
Diffley,
Once and only once upon a time: specifying and regulating origins of DNA replication in eukaryotic cells.
1996,
Pubmed
Elsasser,
Interaction between yeast Cdc6 protein and B-type cyclin/Cdc28 kinases.
1996,
Pubmed
Evan,
Isolation of monoclonal antibodies specific for human c-myc proto-oncogene product.
1985,
Pubmed
,
Xenbase
Forsburg,
The fission yeast cdc19+ gene encodes a member of the MCM family of replication proteins.
1994,
Pubmed
Guttes,
Regulation of DNA replication in the nuclei of the slime mold Physarum polycephalum. Transplantation of nuclei by plasmodial coalescence.
1968,
Pubmed
Hayles,
Temporal order of S phase and mitosis in fission yeast is determined by the state of the p34cdc2-mitotic B cyclin complex.
1994,
Pubmed
Hennessy,
A group of interacting yeast DNA replication genes.
1991,
Pubmed
Hennessy,
Subcellular localization of yeast CDC46 varies with the cell cycle.
1990,
Pubmed
Kearsey,
Cell cycle control of eukaryotic DNA replication.
1996,
Pubmed
Kubota,
Identification of the yeast MCM3-related protein as a component of Xenopus DNA replication licensing factor.
1995,
Pubmed
,
Xenbase
Lei,
Physical interactions among Mcm proteins and effects of Mcm dosage on DNA replication in Saccharomyces cerevisiae.
1996,
Pubmed
Liang,
ORC and Cdc6p interact and determine the frequency of initiation of DNA replication in the genome.
1995,
Pubmed
Madine,
MCM3 complex required for cell cycle regulation of DNA replication in vertebrate cells.
1995,
Pubmed
,
Xenbase
Madine,
The nuclear envelope prevents reinitiation of replication by regulating the binding of MCM3 to chromatin in Xenopus egg extracts.
1995,
Pubmed
,
Xenbase
Maine,
Mutants of S. cerevisiae defective in the maintenance of minichromosomes.
1984,
Pubmed
Micklem,
Yeast origin recognition complex is involved in DNA replication and transcriptional silencing.
1993,
Pubmed
Miyake,
Fission yeast genes nda1+ and nda4+, mutations of which lead to S-phase block, chromatin alteration and Ca2+ suppression, are members of the CDC46/MCM2 family.
1993,
Pubmed
Moir,
Cold-sensitive cell-division-cycle mutants of yeast: isolation, properties, and pseudoreversion studies.
1982,
Pubmed
Moreno,
Regulation of progression through the G1 phase of the cell cycle by the rum1+ gene.
1994,
Pubmed
Nasmyth,
Viewpoint: putting the cell cycle in order.
1996,
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
Rao,
Mammalian cell fusion: studies on the regulation of DNA synthesis and mitosis.
1970,
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
Rowley,
Initiation complex assembly at budding yeast replication origins begins with the recognition of a bipartite sequence by limiting amounts of the initiator, ORC.
1995,
Pubmed
Santocanale,
ORC- and Cdc6-dependent complexes at active and inactive chromosomal replication origins in Saccharomyces cerevisiae.
1996,
Pubmed
Schwob,
The B-type cyclin kinase inhibitor p40SIC1 controls the G1 to S transition in S. cerevisiae.
1994,
Pubmed
Stern,
A quantitative model for the cdc2 control of S phase and mitosis in fission yeast.
1996,
Pubmed
,
Xenbase
Stillman,
Cell cycle control of DNA replication.
1996,
Pubmed
Surana,
Destruction of the CDC28/CLB mitotic kinase is not required for the metaphase to anaphase transition in budding yeast.
1993,
Pubmed
Takahashi,
Fission yeast minichromosome loss mutants mis cause lethal aneuploidy and replication abnormality.
1994,
Pubmed
Whitebread,
Cdc54 belongs to the Cdc46/Mcm3 family of proteins which are essential for initiation of eukaryotic DNA replication.
1995,
Pubmed
Wu,
A yeast plasmid partitioning protein is a karyoskeletal component.
1987,
Pubmed
Yan,
Cell cycle-regulated nuclear localization of MCM2 and MCM3, which are required for the initiation of DNA synthesis at chromosomal replication origins in yeast.
1993,
Pubmed
Yan,
Mcm2 and Mcm3, two proteins important for ARS activity, are related in structure and function.
1991,
Pubmed