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??? Cdc7, a protein kinase required for the initiation of eukaryotic DNA replication, is activated by a regulatory subunit, Dbf4. A second activator of Cdc7 called Drf1 exists in vertebrates, but its function is unknown. Here, we report that in Xenopus egg extracts, Cdc7-Drf1 is far more abundant than Cdc7-Dbf4, and removal of Drf1 but not Dbf4 severely inhibits phosphorylation of Mcm4 and DNA replication. After gastrulation, when the cell cycle acquires somatic characteristics, Drf1 levels decline sharply and Cdc7-Dbf4 becomes the more abundant kinase. These results identify Drf1 as a developmentally regulated, essential activator of Cdc7 in Xenopus.
???displayArticle.pubmedLink???
16204181
???displayArticle.pmcLink???PMC1240038 ???displayArticle.link???Genes Dev ???displayArticle.grants???[+]
Bell,
DNA replication in eukaryotic cells.
2002, Pubmed
Bell,
DNA replication in eukaryotic cells.
2002,
Pubmed
Blow,
Initiation of DNA replication in nuclei and purified DNA by a cell-free extract of Xenopus eggs.
1986,
Pubmed
,
Xenbase
Blow,
Preventing re-replication of DNA in a single cell cycle: evidence for a replication licensing factor.
1993,
Pubmed
,
Xenbase
Brown,
Purification of Hsk1, a minichromosome maintenance protein kinase from fission yeast.
1998,
Pubmed
Costanzo,
An ATR- and Cdc7-dependent DNA damage checkpoint that inhibits initiation of DNA replication.
2003,
Pubmed
,
Xenbase
Furukohri,
Identification and characterization of a Xenopus homolog of Dbf4, a regulatory subunit of the Cdc7 protein kinase required for the initiation of DNA replication.
2003,
Pubmed
,
Xenbase
Hardy,
mcm5/cdc46-bob1 bypasses the requirement for the S phase activator Cdc7p.
1997,
Pubmed
Howe,
Identification of a developmental timer regulating the stability of embryonic cyclin A and a new somatic A-type cyclin at gastrulation.
1995,
Pubmed
,
Xenbase
Jares,
A Xenopus Dbf4 homolog is required for Cdc7 chromatin binding and DNA replication.
2004,
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,
Mammalian Cdc7-Dbf4 protein kinase complex is essential for initiation of DNA replication.
1999,
Pubmed
Johnston,
First the CDKs, now the DDKs.
1999,
Pubmed
Kumagai,
A novel growth- and cell cycle-regulated protein, ASK, activates human Cdc7-related kinase and is essential for G1/S transition in mammalian cells.
1999,
Pubmed
Lee,
The Cdc23 (Mcm10) protein is required for the phosphorylation of minichromosome maintenance complex by the Dfp1-Hsk1 kinase.
2003,
Pubmed
Lei,
Mcm2 is a target of regulation by Cdc7-Dbf4 during the initiation of DNA synthesis.
1997,
Pubmed
Masai,
Human Cdc7-related kinase complex. In vitro phosphorylation of MCM by concerted actions of Cdks and Cdc7 and that of a criticial threonine residue of Cdc7 bY Cdks.
2000,
Pubmed
Montagnoli,
Drf1, a novel regulatory subunit for human Cdc7 kinase.
2002,
Pubmed
Newport,
A major developmental transition in early Xenopus embryos: I. characterization and timing of cellular changes at the midblastula stage.
1982,
Pubmed
,
Xenbase
Newport,
On the coupling between DNA replication and mitosis.
1989,
Pubmed
,
Xenbase
Newport,
A major developmental transition in early Xenopus embryos: II. Control of the onset of transcription.
1982,
Pubmed
,
Xenbase
Pacek,
A requirement for MCM7 and Cdc45 in chromosome unwinding during eukaryotic DNA replication.
2004,
Pubmed
,
Xenbase
Pereverzeva,
Distinct phosphoisoforms of the Xenopus Mcm4 protein regulate the function of the Mcm complex.
2000,
Pubmed
,
Xenbase
Sato,
Human and Xenopus cDNAs encoding budding yeast Cdc7-related kinases: in vitro phosphorylation of MCM subunits by a putative human homologue of Cdc7.
1997,
Pubmed
,
Xenbase
Shechter,
DNA unwinding is an Mcm complex-dependent and ATP hydrolysis-dependent process.
2004,
Pubmed
,
Xenbase
Shechter,
ATR and ATM regulate the timing of DNA replication origin firing.
2004,
Pubmed
,
Xenbase
Takahashi,
Pumps, paradoxes and ploughshares: mechanism of the MCM2-7 DNA helicase.
2005,
Pubmed
Takahashi,
Recruitment of Xenopus Scc2 and cohesin to chromatin requires the pre-replication complex.
2004,
Pubmed
,
Xenbase
Takeda,
Regulation of initiation of S phase, replication checkpoint signaling, and maintenance of mitotic chromosome structures during S phase by Hsk1 kinase in the fission yeast.
2001,
Pubmed
Walter,
Initiation of eukaryotic DNA replication: origin unwinding and sequential chromatin association of Cdc45, RPA, and DNA polymerase alpha.
2000,
Pubmed
,
Xenbase
Walter,
Regulated chromosomal DNA replication in the absence of a nucleus.
1998,
Pubmed
,
Xenbase
Walter,
Evidence for sequential action of cdc7 and cdk2 protein kinases during initiation of DNA replication in Xenopus egg extracts.
2000,
Pubmed
,
Xenbase
Weinreich,
Cdc7p-Dbf4p kinase binds to chromatin during S phase and is regulated by both the APC and the RAD53 checkpoint pathway.
1999,
Pubmed
Yanow,
Xenopus Drf1, a regulator of Cdc7, displays checkpoint-dependent accumulation on chromatin during an S-phase arrest.
2003,
Pubmed
,
Xenbase
Yoshizawa-Sugata,
A second human Dbf4/ASK-related protein, Drf1/ASKL1, is required for efficient progression of S and M phases.
2005,
Pubmed
