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Gene Review

CDC7  -  Cdc7p

Saccharomyces cerevisiae S288c

Synonyms: Cell division control protein 7, D2855, LSD6, OAF2, SAS1, ...
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Disease relevance of CDC7


High impact information on CDC7

  • The analysis described here suggests a model in which one function of Dbf4 may be to recruit the Cdc7 protein kinase to initiation complexes [3].
  • The Dbf4 protein interacts with and positively regulates the activity of the Cdc7 protein kinase, which is required for entry into S phase in the yeast mitotic cell cycle [3].
  • An active Clb/Cdc28 kinase complex, or its vertebrate equivalent, is required in trans to stimulate initiation in G(1)-phase nuclei, whereas the Dbf4/Cdc7 kinase complex must be provided by the template nuclei themselves [4].
  • Previous experiments have shown that the essential function of Cdc7 is executed near the G1-S boundary; after Start but before the elongation phase of DNA replication [5].
  • Cdc7 is required throughout the yeast S phase to activate replication origins [6].

Biological context of CDC7

  • CDC45 is required in conjunction with CDC7/DBF4 to trigger the initiation of DNA replication [7].
  • These data indicate that CDC45 functions in late G1 phase in concert with CDC7/DBF4 to trigger initiation at replication origins after the assembly of the prereplicative complexes [7].
  • CDC7 encodes a protein kinase activity, and we now show that this kinase activity varies in the cell cycle but that protein levels appear to remain constant [2].
  • We present several lines of evidence that periodic activation of CDC7 kinase is at least in part through phosphorylation [2].
  • An analysis of cell cycle arrest indicates the existence of (at least) two checkpoints for damaged DNA prior to S-phase; one at START (a G1 checkpoint characterized by pheromone sensitivity of arrested cells) and one between the CDC4- and CDC7-mediated steps (termed the G1/S checkpoint) [8].

Anatomical context of CDC7


Associations of CDC7 with chemical compounds

  • DNA metabolism gene CDC7 from yeast encodes a serine (threonine) protein kinase [12].
  • Saccharomyces cerevisiae CDC7 encodes a serine/threonine kinase required for G(1)/S transition, and its related kinases are present in fission yeast as well as in higher eukaryotes, including humans [13].
  • Cdc7 protein carrying a serine to alanine change in the consensus recognition site for Cdc28 kinase shows an altered phosphopeptide map, suggesting that this site is important in determining the overall Cdc7 phosphorylation pattern [2].
  • This is because Cdc7 is still required for the activation of late-firing origins after the hydroxyurea block [5].
  • Using this approach, we developed an assay for Cdc7/Dbf4 kinase activity, determined the K(m) for ATP, and identified rottlerin as a non-ATP competitive inhibitor of this enzyme [14].

Physical interactions of CDC7

  • It associates with Dfp1/Him1 to form an active complex equivalent to the Cdc7-Dbf4 protein kinase in Saccharomyces cerevisiae [15].
  • Evidence obtained from yeast and Xenopus indicate the initiation of DNA replication to be a two-step process: the origin recognition complex, Cdc6 and Mcm proteins are required for establishing the prereplicative complex and the activities of Cdks and of Cdc7 kinase then trigger the G1-S transition [16].

Enzymatic interactions of CDC7

  • CDC7 immune complexes prepared from yeast with these antibodies phosphorylate histone H1 [17].

Regulatory relationships of CDC7


Other interactions of CDC7

  • We propose a model in which Dbf4p targets Cdc7p to the prereplication complex prior to the G(1)/S transition, by a pathway parallel to, but independent of, the Cdc6p-dependent recruitment of MCMs [4].
  • The observed semiconservative replication is compromised in S-phase nuclear extracts deficient for the Cdk1 kinase (Cdc28p) but not in extracts deficient for the Cdc7p kinase [20].
  • The accumulation of CDC9 mRNA in late G1 is dependent upon the completion of start but not the CDC7 and CDC8 functions [21].
  • Finally, activation of the DNA damage checkpoint and the resulting cell cycle delay is intact in cdc7Delta mcm5-bob1 cells, suggesting a direct role for CDC7 in DNA repair/damage tolerance [22].
  • Mutant alleles of cdc7 and cdc14 were also isolated in the orc2-1 synthetic lethal screen [23].

Analytical, diagnostic and therapeutic context of CDC7


  1. Cdc7p-Dbf4p kinase binds to chromatin during S phase and is regulated by both the APC and the RAD53 checkpoint pathway. Weinreich, M., Stillman, B. EMBO J. (1999) [Pubmed]
  2. Regulation of Saccharomyces cerevisiae CDC7 function during the cell cycle. Yoon, H.J., Loo, S., Campbell, J.L. Mol. Biol. Cell (1993) [Pubmed]
  3. Interaction of Dbf4, the Cdc7 protein kinase regulatory subunit, with yeast replication origins in vivo. Dowell, S.J., Romanowski, P., Diffley, J.F. Science (1994) [Pubmed]
  4. A role for the Cdc7 kinase regulatory subunit Dbf4p in the formation of initiation-competent origins of replication. Pasero, P., Duncker, B.P., Schwob, E., Gasser, S.M. Genes Dev. (1999) [Pubmed]
  5. The Cdc7 protein kinase is required for origin firing during S phase. Bousset, K., Diffley, J.F. Genes Dev. (1998) [Pubmed]
  6. Cdc7 is required throughout the yeast S phase to activate replication origins. Donaldson, A.D., Fangman, W.L., Brewer, B.J. Genes Dev. (1998) [Pubmed]
  7. CDC45 is required in conjunction with CDC7/DBF4 to trigger the initiation of DNA replication. Owens, J.C., Detweiler, C.S., Li, J.J. Proc. Natl. Acad. Sci. U.S.A. (1997) [Pubmed]
  8. Characterization of G1 checkpoint control in the yeast Saccharomyces cerevisiae following exposure to DNA-damaging agents. Siede, W., Friedberg, A.S., Dianova, I., Friedberg, E.C. Genetics (1994) [Pubmed]
  9. A human homolog of the yeast CDC7 gene is overexpressed in some tumors and transformed cell lines. Hess, G.F., Drong, R.F., Weiland, K.L., Slightom, J.L., Sclafani, R.A., Hollingsworth, R.E. Gene (1998) [Pubmed]
  10. Cell cycle inhibition of yeast spheroplasts. Murakami, S., Livingston, D.M. Mol. Gen. Genet. (1982) [Pubmed]
  11. Functions of mammalian Cdc7 kinase in initiation/monitoring of DNA replication and development. Kim, J.M., Yamada, M., Masai, H. Mutat. Res. (2003) [Pubmed]
  12. DNA metabolism gene CDC7 from yeast encodes a serine (threonine) protein kinase. Hollingsworth, R.E., Sclafani, R.A. Proc. Natl. Acad. Sci. U.S.A. (1990) [Pubmed]
  13. A fission yeast gene, him1(+)/dfp1(+), encoding a regulatory subunit for Hsk1 kinase, plays essential roles in S-phase initiation as well as in S-phase checkpoint control and recovery from DNA damage. Takeda, T., Ogino, K., Matsui, E., Cho, M.K., Kumagai, H., Miyake, T., Arai, K., Masai, H. Mol. Cell. Biol. (1999) [Pubmed]
  14. A generic time-resolved fluorescence assay for serine/threonine kinase activity: application to Cdc7/Dbf4. Xu, K., Stern, A.S., Levin, W., Chua, A., Vassilev, L.T. J. Biochem. Mol. Biol. (2003) [Pubmed]
  15. Hsk1-Dfp1/Him1, the Cdc7-Dbf4 kinase in Schizosaccharomyces pombe, associates with Swi1, a component of the replication fork protection complex. Matsumoto, S., Ogino, K., Noguchi, E., Russell, P., Masai, H. J. Biol. Chem. (2005) [Pubmed]
  16. Cyclin-dependent kinases at the G1-S transition of the mammalian cell cycle. Hengstschläger, M., Braun, K., Soucek, T., Miloloza, A., Hengstschläger-Ottnad, E. Mutat. Res. (1999) [Pubmed]
  17. The CDC7 protein of Saccharomyces cerevisiae is a phosphoprotein that contains protein kinase activity. Yoon, H.J., Campbell, J.L. Proc. Natl. Acad. Sci. U.S.A. (1991) [Pubmed]
  18. Genetic interactions between CDC7 and CDC28: growth inhibition of cdc28-1N by Cdc7 point mutants. Ohtoshi, A., Arai, K., Masai, H. Genes Cells (1996) [Pubmed]
  19. Temperature-sensitive cdc7 mutations of Saccharomyces cerevisiae are suppressed by the DBF4 gene, which is required for the G1/S cell cycle transition. Kitada, K., Johnston, L.H., Sugino, T., Sugino, A. Genetics (1992) [Pubmed]
  20. Cyclin B-cdk1 kinase stimulates ORC- and Cdc6-independent steps of semiconservative plasmid replication in yeast nuclear extracts. Duncker, B.P., Pasero, P., Braguglia, D., Heun, P., Weinreich, M., Gasser, S.M. Mol. Cell. Biol. (1999) [Pubmed]
  21. Regulation of CDC9, the Saccharomyces cerevisiae gene that encodes DNA ligase. Peterson, T.A., Prakash, L., Prakash, S., Osley, M.A., Reed, S.I. Mol. Cell. Biol. (1985) [Pubmed]
  22. CDC7/DBF4 functions in the translesion synthesis branch of the RAD6 epistasis group in Saccharomyces cerevisiae. Pessoa-Brandão, L., Sclafani, R.A. Genetics (2004) [Pubmed]
  23. Characterization of an essential Orc2p-associated factor that plays a role in DNA replication. Hardy, C.F. Mol. Cell. Biol. (1996) [Pubmed]
  24. hsk1+, a Schizosaccharomyces pombe gene related to Saccharomyces cerevisiae CDC7, is required for chromosomal replication. Masai, H., Miyake, T., Arai, K. EMBO J. (1995) [Pubmed]
  25. Cloning of the CDC7 gene of Saccharomyces cerevisiae in association with centromeric DNA. Meddle, C.C., Kumar, P., Ham, J., Hughes, D.A., Johnston, I.R. Gene (1985) [Pubmed]
  26. SEPH, a Cdc7p orthologue from Aspergillus nidulans, functions upstream of actin ring formation during cytokinesis. Bruno, K.S., Morrell, J.L., Hamer, J.E., Staiger, C.J. Mol. Microbiol. (2001) [Pubmed]
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