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cdc25 Phosphatasescdc42 GTP-Binding ProteinCDC2 Protein KinaseCdc20 ProteinsCDC28 Protein Kinase, S cerevisiaeCell Cycle Proteinscdc42 GTP-Binding Protein, Saccharomyces cerevisiaeCDC2-CDC28 KinasesGenes, cdcMitosisCyclin BSaccharomyces cerevisiae ProteinsCell CycleFungal ProteinsSaccharomyces cerevisiaeSchizosaccharomycesUbiquitin-Protein Ligase ComplexesAnaphase-Promoting Complex-CyclosomeSchizosaccharomyces pombe Proteinsras-GRF1PhosphorylationG2 PhaseMolecular Sequence DataProtein-Serine-Threonine KinasesAmino Acid Sequencerac1 GTP-Binding ProteinCenters for Disease Control and Prevention (U.S.)Cyclin B1Protein KinasesMutationS PhaseCyclinsProtein Bindingp21-Activated KinasesCyclin-Dependent Kinasesrho GTP-Binding ProteinsProtamine Kinaserac GTP-Binding ProteinsGenes, FungalApc8 Subunit, Anaphase-Promoting Complex-CyclosomeDNA ReplicationGuanine Nucleotide Exchange FactorsNuclear ProteinsF-Box ProteinsEnzyme ActivationRecombinant Fusion ProteinsGTP PhosphohydrolasesMaturation-Promoting FactorSequence Homology, Amino AcidGTPase-Activating ProteinsAnaphasePhosphoprotein PhosphatasesProtein Tyrosine PhosphatasesG1 PhaseSpindle ApparatusHeLa CellsGene Expression Regulation, FungalApc6 Subunit, Anaphase-Promoting Complex-CyclosomeDNA, FungalUbiquitin-Protein LigasesUbiquitin-Conjugating EnzymesActinsGTP-Binding ProteinsBase SequenceSaccharomycetalesSignal TransductionCdh1 ProteinsCell PolarityCyclin-Dependent Kinase 2rhoA GTP-Binding ProteinChaperoninsXenopusLigasesProtein Structure, TertiaryOrigin Recognition ComplexCell DivisionMeiosisWiskott-Aldrich Syndrome Protein, NeuronalXenopus ProteinsMad2 ProteinsCloning, MolecularModels, Biologicalras GTPase-Activating ProteinsDNA-Binding ProteinsSuppression, GeneticCyclin ACytokinesisCell LinePseudopodiaOocytesCarrier ProteinsTwo-Hybrid System TechniquesBinding SitesCytoskeletonStarfishWiskott-Aldrich Syndrome ProteinInterphase14-3-3 ProteinsUnited StatesTemperature
DBF4Inhibition of CDC7LocalizationInitiationReplicationKinase activityVitroCdksChromatinNovel rolesRolesVivoMolecularHumanEssentialFunctionLevels
DBF411
  • We show here that multiple phosphorylation sites within Rec8 as well as two different kinases, casein kinase 1delta/epsilon (CK1delta/epsilon) and Dbf4-dependent Cdc7 kinase (DDK), are required for Rec8 cleavage and meiosis I nuclear division. (nih.gov)
  • CDC7 is a cell cycle kinase that is activated through a physical interaction with regulatory subunits, DBF4 or DRF1. (grantome.com)
  • DRF1 represents the activator of CDC7 during embryogenesis, while DBF4 functions mainly during divisions of somatic cells. (grantome.com)
  • The DBF4-CDC7 kinase becomes activated at the end of G1 phase and phosphorylates components of the pre-replication complexes (pre-RCs), thereby triggering entry of cells into DNA synthesis phase (S phase). (grantome.com)
  • Moreover, mutant p53 cells exhibit enhanced levels of Dbf4, promoting the activity of Cdc7/Dbf4 complex. (isical.ac.in)
  • 2. Molecular mechanism of activation of human Cdc7 kinase: bipartite interaction with Dbf4/activator of S phase kinase (ASK) activation subunit stimulates ATP binding and substrate recognition. (nih.gov)
  • 9. ATR-Chk1-APC/CCdh1-dependent stabilization of Cdc7-ASK (Dbf4) kinase is required for DNA lesion bypass under replication stress. (nih.gov)
  • 14. The replication kinase Cdc7-Dbf4 promotes the interaction of the p150 subunit of chromatin assembly factor 1 with proliferating cell nuclear antigen. (nih.gov)
  • In particular this project will aim to define the reciprocal roles of the two cellular Cdc7 complexes, Cdc7/Dbf4 and Cdc7/Drf1, by defining their reciprocal cellular localization, by identifying novel substrates and by conducting large-scale genome wide loss of function synthetic lethality screenings. (fems-microbiology.org)
  • Among the top fifteen hits of essential gene conditional mutant alleles with a negative interaction with Cse4-OE, we identified five alleles of the Cdc7-Dbf4 kinase complex, which is evolutionarily conserved and essential for DNA replication initiation. (nih.gov)
  • Furthermore, Cdc7 and Cse4 interacted in vivo, and in vitro kinase assays showed that the Cdc7-Dbf4 kinase complex phosphorylates Cse4. (nih.gov)
Inhibition of CDC74
  • The overarching goal of this proposal is to test whether inhibition of CDC7 kinase might represent a powerful therapeutic strategy in treatment of human cancers carrying mutated p53 protein. (grantome.com)
  • This study will test whether inhibition of CDC7 kinase might represent a powerful therapeutic strategy for treatment of a subset of human cancers. (grantome.com)
  • 1. Nuclear PGK1 Alleviates ADP-Dependent Inhibition of CDC7 to Promote DNA Replication. (nih.gov)
  • Cdc7 kinase is a key regulator of DNA replication and cell cycle progression and inhibition of Cdc7 is an emerging strategy for the treatment of human cancers. (fems-microbiology.org)
Localization4
  • 5. Cell cycle regulation of chromatin binding and nuclear localization of human Cdc7-ASK kinase complex. (nih.gov)
  • Biochemical analysis showed defects in degradation, ubiquitination, and localization of Cse4 in cdc7 mutants. (nih.gov)
  • Defects in Cse4 localization and chromosome segregation as well as SL in the presence of Cse4-OE were also observed in cdc7 mcm5 mutant strains which do not exhibit defects in DNA replication. (nih.gov)
  • These data indicate that Cdc7 regulates Cse4 localization independently of its role in the initiation of DNA replication. (nih.gov)
Initiation8
  • Here, we show that enhanced Cdc7-dependent replication initiation enables mutant p53 to confer oncogenic phenotypes. (isical.ac.in)
  • Chromatin enrichment of replication initiation factors and subsequent increase in origin firing confirm increased Cdc7-dependent replication initiation in mutant p53 cells. (isical.ac.in)
  • We propose that increased Cdc7-dependent replication initiation is a hallmark of p53 gain-of-function mutations. (isical.ac.in)
  • 4. A Cdc7 kinase inhibitor restricts initiation of DNA replication and has antitumor activity. (nih.gov)
  • 12. Protein phosphatase 2A and Cdc7 kinase regulate the DNA unwinding element-binding protein in replication initiation. (nih.gov)
  • 18. p53 gain-of-function mutations increase Cdc7-dependent replication initiation. (nih.gov)
  • An ATR- and Cdc7-dependent DNA damage checkpoint that inhibits initiation of DNA replication. (xenbase.org)
  • Fission yeast Cdc7 is essential for cell division by playing a key role in the initiation of septum formation and cytokinesis. (umbc.edu)
Replication5
  • p53 gain-of-function mutations increase Cdc7-dependent replication ini" by Arindam Datta, Dishari Ghatak et al. (isical.ac.in)
  • 8. Cdc7 kinase mediates Claspin phosphorylation in DNA replication checkpoint. (nih.gov)
  • 11. Regulation and roles of Cdc7 kinase under replication stress. (nih.gov)
  • 13. Cdc7-dependent and -independent phosphorylation of Claspin in the induction of the DNA replication checkpoint. (nih.gov)
  • 19. A novel Cdk2 interactor is phosphorylated by Cdc7 and associates with components of the replication complexes. (nih.gov)
Kinase activity2
  • Depletion of CDC7 protein, or inhibition of its kinase activity in p53-mutant cancer cells was shown to trigger tumor cell apoptosis. (grantome.com)
  • [4] This process depends on the kinase activity of Cdc7 and various S-phase CDKs, both of which are upregulated upon S-phase entry. (wikipedia.org)
Vitro2
  • Further, knockdown of CDC7 significantly abrogates mutant p53-driven cancer phenotypes in vitro and in vivo. (isical.ac.in)
  • In vitro phosphorylation of MCM by concerted actions of Cdks and Cdc7 and that of a criticial threonine residue of Cdc7 bY Cdks. (nih.gov)
Cdks1
  • After Cdc7 and S-phase CDKs phosphorylate their respective substrates, a second set of replicative factors associate with the pre-RC. (wikipedia.org)
Chromatin1
Novel roles2
  • The expected overall impact of this proposal is that it will change our understanding of mechanisms governing cell division, will elucidate novel roles of CDC7 in tumorigenesis, and will test the utility of targeting CDC7 in cancer treatment. (grantome.com)
  • The project will investigate novel roles of the Cdc7 kinase in human cells. (fems-microbiology.org)
Roles1
  • In Aim 2, we will analyze additional functions of CDC7 in human cancer cells, through which CDC7 may play important roles in tumorigenesis. (grantome.com)
Vivo1
  • We demonstrate that mutant p53 cooperates with the oncogenic transcription factor Myb in vivo and transactivates Cdc7 in cancer cells. (isical.ac.in)
Molecular2
  • These mice and cells derived from them offer us tools to study the molecular functions of CDC7. (grantome.com)
  • In Aim 1, we will study the molecular role of CDC7 in cell division of normal, non-transformed cells. (grantome.com)
Human3
  • Several reports documented that human cancer cells with mutated p53 are particularly sensitive to CDC7 inhibition. (grantome.com)
  • CDC7 protein is a cell cycle kinase that is found at abnormally high levels in several types of human tumors. (grantome.com)
  • 7. Human Cdc7-related kinase complex. (nih.gov)
Essential1
Function1
  • To circumvent this limitation, and to study CDC7 function at later stages, our laboratory developed a novel mouse strain that allows us to turn off CDC7 protein. (grantome.com)
Levels1
  • In summary, we have identified potential therapeutic targets for CENPA-OE tumors and provide insights into a novel mechanistic role of Cdc7 in regulating CENP-A/Cse4 levels for genome stability. (nih.gov)