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Gene Review

CDC7  -  cell division cycle 7

Homo sapiens

Synonyms: CDC7-related kinase, CDC7L1, Cell division cycle 7-related protein kinase, HsCDC7, HsCdc7, ...
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Disease relevance of CDC7

  • We found that Cdc7 phosphorylates Mcm2 in at least three different sites, one of which corresponds to a site also reported to be phosphorylated by ataxia telangiectasia and Rad3-related [1].

High impact information on CDC7


Biological context of CDC7


Anatomical context of CDC7


Associations of CDC7 with chemical compounds

  • CDC7 kinase phosphorylates serine residues adjacent to acidic amino acids in the minichromosome maintenance 2 protein [4].
  • Among four possible Cdk phosphorylation sites of huCdc7, replacement of Thr-376, corresponding to the activating threonine of Cdk, with alanine (T376A mutant) dramatically reduces kinase activity, indicative of kinase activation by phosphorylation of this residue [9].
  • We have developed new immnunological reagents to study the properties of human Cdc7 kinase in cells challenged with the ribonucleotide reductase inhibitor hydroxyurea or with the DNA topoisomerase II inhibitor etoposide [7].
  • HsCdc7 contains the conserved subdomains common to all protein-serine/threonine kinases and three "kinase inserts" that are characteristic of Cdc7p and Hsk1 [10].
  • In stable transformants expressing GFP-fused full-length ASK under the tetracycline inducible promoter, GFP-ASK protein accumulates in nuclei at the telophase, but its binding to chromatin does not reach a maximum until late G1, whereas huCdc7 is imported into nuclei and binds to chromatin at early G1 [11].

Physical interactions of CDC7

  • CONCLUSIONS: Nuclear localization and chromatin binding of endogenous huCdc7 and GFP-ASK expressed during the post-mitotic phase are independently regulated [11].

Enzymatic interactions of CDC7

  • MCM4 and MCM6 are also phosphorylated by huCdc7 albeit to less extent [9].
  • ASK forms an active kinase complex with huCdc7 that is capable of phosphorylating MCM2 protein [12].
  • These results, together with the functions of Cdc7p in yeast, suggest that HsCdc7 may phosphorylate critical substrate(s) that regulate the G1/S phase transition and/or DNA replication in mammalian cells [10].

Regulatory relationships of CDC7


Other interactions of CDC7

  • Furthermore, mitotic progression is retarded in ASKL1 or Cdc7 siRNA-treated cells [5].
  • Conversely, CAF1 recruitment is reduced in a PCNA/DNA loading assay using Cdc7-depleted extracts [6].
  • Cdc7-Dbf4 kinase is conserved through evolution and regulates initiation and progression of DNA replication [5].
  • Indeed, over-expression of both huCdc7 and ASK results in the elevated phosphorylation of endogenous MCM2 protein, as manifested by appearance of the mobility-shifted form on SDS-PAGE, but does not cause any significant effects on cell cycle progression [11].
  • Cdc7 inhibition reveals a p53-dependent replication checkpoint that is defective in cancer cells [8].

Analytical, diagnostic and therapeutic context of CDC7


  1. Identification of Mcm2 phosphorylation sites by S-phase-regulating kinases. Montagnoli, A., Valsasina, B., Brotherton, D., Troiani, S., Rainoldi, S., Tenca, P., Molinari, A., Santocanale, C. J. Biol. Chem. (2006) [Pubmed]
  2. Mammalian Cdc7-Dbf4 protein kinase complex is essential for initiation of DNA replication. Jiang, W., McDonald, D., Hope, T.J., Hunter, T. EMBO J. (1999) [Pubmed]
  3. Human and Xenopus cDNAs encoding budding yeast Cdc7-related kinases: in vitro phosphorylation of MCM subunits by a putative human homologue of Cdc7. Sato, N., Arai, K., Masai, H. EMBO J. (1997) [Pubmed]
  4. CDC7 kinase phosphorylates serine residues adjacent to acidic amino acids in the minichromosome maintenance 2 protein. Cho, W.H., Lee, Y.J., Kong, S.I., Hurwitz, J., Lee, J.K. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  5. A second human Dbf4/ASK-related protein, Drf1/ASKL1, is required for efficient progression of S and M phases. Yoshizawa-Sugata, N., Ishii, A., Taniyama, C., Matsui, E., Arai, K., Masai, H. J. Biol. Chem. (2005) [Pubmed]
  6. The replication kinase Cdc7-Dbf4 promotes the interaction of the p150 subunit of chromatin assembly factor 1 with proliferating cell nuclear antigen. Gérard, A., Koundrioukoff, S., Ramillon, V., Sergère, J.C., Mailand, N., Quivy, J.P., Almouzni, G. EMBO Rep. (2006) [Pubmed]
  7. Cdc7 is an active kinase in human cancer cells undergoing replication stress. Tenca, P., Brotherton, D., Montagnoli, A., Rainoldi, S., Albanese, C., Santocanale, C. J. Biol. Chem. (2007) [Pubmed]
  8. Cdc7 inhibition reveals a p53-dependent replication checkpoint that is defective in cancer cells. Montagnoli, A., Tenca, P., Sola, F., Carpani, D., Brotherton, D., Albanese, C., Santocanale, C. Cancer Res. (2004) [Pubmed]
  9. 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. Masai, H., Matsui, E., You, Z., Ishimi, Y., Tamai, K., Arai, K. J. Biol. Chem. (2000) [Pubmed]
  10. Identification and characterization of a human protein kinase related to budding yeast Cdc7p. Jiang, W., Hunter, T. Proc. Natl. Acad. Sci. U.S.A. (1997) [Pubmed]
  11. Cell cycle regulation of chromatin binding and nuclear localization of human Cdc7-ASK kinase complex. Sato, N., Sato, M., Nakayama, M., Saitoh, R., Arai, K., Masai, H. Genes Cells (2003) [Pubmed]
  12. A novel growth- and cell cycle-regulated protein, ASK, activates human Cdc7-related kinase and is essential for G1/S transition in mammalian cells. Kumagai, H., Sato, N., Yamada, M., Mahony, D., Seghezzi, W., Lees, E., Arai, K., Masai, H. Mol. Cell. Biol. (1999) [Pubmed]
  13. Identification and characterization of human cdc7 nuclear retention and export sequences in the context of chromatin binding. Kim, B.J., Kim, S.Y., Lee, H. J. Biol. Chem. (2007) [Pubmed]
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