CDC7/YDL017W Summary Help

Standard Name CDC7 1
Systematic Name YDL017W
Alias LSD6 , SAS1 2
Feature Type ORF, Verified
Description DDK (Dbf4-dependent kinase) catalytic subunit; required for origin firing and replication fork progression in mitotic S phase through phosphorylation of Mcm2-7p complexes and Cdc45p; kinase activity correlates with cyclical DBF4 expression; required for pre-meiotic DNA replication, meiotic DSB formation, recruitment of the monopolin complex to kinetochores during meiosis I and as a gene-specific regulator of the meiosis-specific transcription factor Ndt80p (3, 4, 5, 6, 7 and see Summary Paragraph)
Name Description Cell Division Cycle 8
Chromosomal Location
ChrIV:424209 to 425732 | ORF Map | GBrowse
Gbrowse
Genetic position: -1 cM
Gene Ontology Annotations All CDC7 GO evidence and references
  View Computational GO annotations for CDC7
Molecular Function
Manually curated
Biological Process
Manually curated
Cellular Component
Manually curated
Regulators 4 genes
Resources
Classical genetics
conditional
Large-scale survey
conditional
null
reduction of function
Resources
317 total interaction(s) for 201 unique genes/features.
Physical Interactions
  • Affinity Capture-MS: 25
  • Affinity Capture-Western: 16
  • Biochemical Activity: 26
  • Co-purification: 4
  • Protein-peptide: 1
  • Reconstituted Complex: 9
  • Two-hybrid: 23

Genetic Interactions
  • Dosage Growth Defect: 1
  • Dosage Lethality: 5
  • Dosage Rescue: 6
  • Negative Genetic: 95
  • Phenotypic Enhancement: 2
  • Phenotypic Suppression: 4
  • Positive Genetic: 10
  • Synthetic Growth Defect: 55
  • Synthetic Lethality: 20
  • Synthetic Rescue: 15

Resources
Expression Summary
histogram
Resources
Length (a.a.) 507
Molecular Weight (Da) 58,320
Isoelectric Point (pI) 5.72
Localization
Phosphorylation PhosphoGRID | PhosphoPep Database
Structure
Homologs
sequence information
ChrIV:424209 to 425732 | ORF Map | GBrowse
SGD ORF map
Genetic position: -1 cM
Last Update Coordinates: 2011-02-03 | Sequence: 1996-07-31
Subfeature details
Relative
Coordinates
Chromosomal
Coordinates
Most Recent Updates
Coordinates Sequence
CDS 1..1524 424209..425732 2011-02-03 1996-07-31
Retrieve sequences
Analyze Sequence
S288C only
S288C vs. other species
S288C vs. other strains
Resources
External Links All Associated Seq | E.C. | Entrez Gene | Entrez RefSeq Protein | MIPS | Search all NCBI (Entrez) | UniProtKB
Primary SGDIDS000002175
SUMMARY PARAGRAPH for CDC7

Cdc7p is an essential serine/threonine protein kinase whose activity is required throughout S phase for replication origin firing (9, 10; reviewed in 11 12 13, 14, 15, 16, 17, 18, 19). Mutations in CDC7 cause cell cycle arrest after START but before the hydroxyurea arrest point (20, 21).

Cdc7p is regulated by varying levels of Dbf4p, the same way that CDKs are regulated by cyclins. Cdc7p is the catalytic subunit, activated by association with Dbf4p during late G1 (22, 23). The Cdc7p-Dbf4p complex interacts physically with replication origins: Cdc7p interacts with Orc2p, a component of the origin recognition complex (24), and Dbf4p interacts with origin DNA (25).

Several lines of evidence suggest that members of the Mcm2-7 protein family are the most likely candidates for in vivo Cdc7p-Dbf4p substrates. Mcm2p and other Mcm2-7 proteins are in vitro substrates for Cdc7p-Dbf4p kinase activity, and the phosphorylation of Mcm2p in vivo depends upon Cdc7p-Dbf4p (26). Further, a mutation in MCM5/CDC46 can bypass the requirement for Cdc7p kinase activity in initiating DNA synthesis (22, 27). Results of two-hybrid and GST-Mcm2p fusion affinity column chromatography showed that Cdc7p and Dbf4p interact physically with Mcm2p (26).

Homologs of Cdc7p have been identified in S. pombe (28, 29), Xenopus, mouse, and human (30, 31, 32), and a Dbf4p homolog exists in S. pombe (29); evidence suggests that the homologs may perform the same function as the S. cerevisiae proteins. The Xenopus Cdc7p homolog is required for DNA replication in vivo and in vitro (33), and mutations in the S. pombe homolog (hsk1 ) can block the initiation of DNA replication (29). The human and S. pombe Cdc7p homologs can phosphorylate Mcm2-7 proteins in vitro (30, 29).

Last updated: 1999-04-12 Contact SGD

References cited on this page View Complete Literature Guide for CDC7
1) Hartwell LH, et al.  (1973) Genetic Control of the Cell Division Cycle in Yeast: V. Genetic Analysis of cdc Mutants. Genetics 74(2):267-286
2) Axelrod A and Rine J  (1991) A role for CDC7 in repression of transcription at the silent mating-type locus HMR in Saccharomyces cerevisiae. Mol Cell Biol 11(2):1080-91
3) Bell SP and Dutta A  (2002) DNA replication in eukaryotic cells. Annu Rev Biochem 71():333-74
4) Valentin G, et al.  (2006) Dual role of the Cdc7-regulatory protein Dbf4 during yeast meiosis. J Biol Chem 281(5):2828-34
5) Wan L, et al.  (2006) Chemical inactivation of cdc7 kinase in budding yeast results in a reversible arrest that allows efficient cell synchronization prior to meiotic recombination. Genetics 174(4):1767-74
6) Matos J, et al.  (2008) Dbf4-dependent CDC7 kinase links DNA replication to the segregation of homologous chromosomes in meiosis I. Cell 135(4):662-78
7) Lo HC, et al.  (2012) Cdc7-Dbf4 is a gene-specific regulator of meiotic transcription in yeast. Mol Cell Biol 32(2):541-57
8) Hartwell LH, et al.  (1970) Genetic control of the cell-division cycle in yeast. I. Detection of mutants. Proc Natl Acad Sci U S A 66(2):352-9
9) Bousset K and Diffley JF  (1998) The Cdc7 protein kinase is required for origin firing during S phase. Genes Dev 12(4):480-90
10) Donaldson AD, et al.  (1998) Cdc7 is required throughout the yeast S phase to activate replication origins. Genes Dev 12(4):491-501
11) Leatherwood J  (1998) Emerging mechanisms of eukaryotic DNA replication initiation. Curr Opin Cell Biol 10(6):742-8
12) Dutta A and Bell SP  (1997) Initiation of DNA replication in eukaryotic cells. Annu Rev Cell Dev Biol 13():293-332
13) Piatti S  (1997) Cell cycle regulation of S phase entry in Saccharomyces cerevisiae. Prog Cell Cycle Res 3():143-56
14) Toone WM, et al.  (1997) Getting started: regulating the initiation of DNA replication in yeast. Annu Rev Microbiol 51:125-49
15) Stillman B  (1996) Cell cycle control of DNA replication. Science 274(5293):1659-64
16) Bell SP  (1995) Eukaryotic replicators and associated protein complexes. Curr Opin Genet Dev 5(2):162-7
17) Diffley JF, et al.  (1995) Stepwise assembly of initiation complexes at budding yeast replication origins during the cell cycle. J Cell Sci Suppl 19:67-72
18) Sclafani RA and Jackson AL  (1994) Cdc7 protein kinase for DNA metabolism comes of age. Mol Microbiol 11(5):805-10
19) Sherlock G and Rosamond J  (1993) Starting to cycle: G1 controls regulating cell division in budding yeast. J Gen Microbiol 139(11):2531-41
20) Hereford LM and Hartwell LH  (1974) Sequential gene function in the initiation of Saccharomyces cerevisiae DNA synthesis. J Mol Biol 84(3):445-61
21) Hartwell LH  (1976) Sequential function of gene products relative to DNA synthesis in the yeast cell cycle. J Mol Biol 104(4):803-17
22) Jackson AL, et al.  (1993) Cell cycle regulation of the yeast Cdc7 protein kinase by association with the Dbf4 protein. Mol Cell Biol 13(5):2899-908
23) Kitada K, et al.  (1993) A multicopy suppressor gene of the Saccharomyces cerevisiae G1 cell cycle mutant gene dbf4 encodes a protein kinase and is identified as CDC5. Mol Cell Biol 13(7):4445-57
24) Hardy CF  (1996) Characterization of an essential Orc2p-associated factor that plays a role in DNA replication. Mol Cell Biol 16(4):1832-41
25) Dowell SJ, et al.  (1994) Interaction of Dbf4, the Cdc7 protein kinase regulatory subunit, with yeast replication origins in vivo. Science 265(5176):1243-6
26) Lei M, et al.  (1997) Mcm2 is a target of regulation by Cdc7-Dbf4 during the initiation of DNA synthesis. Genes Dev 11(24):3365-74
27) Hardy CF, et al.  (1997) mcm5/cdc46-bob1 bypasses the requirement for the S phase activator Cdc7p. Proc Natl Acad Sci U S A 94(7):3151-5
28) Masai H, et al.  (1995) hsk1+, a Schizosaccharomyces pombe gene related to Saccharomyces cerevisiae CDC7, is required for chromosomal replication. EMBO J 14(13):3094-104
29) Brown GW and Kelly TJ  (1998) Purification of Hsk1, a minichromosome maintenance protein kinase from fission yeast. J Biol Chem 273(34):22083-90
30) Sato N, et al.  (1997) Human and Xenopus cDNAs encoding budding yeast Cdc7-related kinases: in vitro phosphorylation of MCM subunits by a putative human homologue of Cdc7. EMBO J 16(14):4340-51
31) Jiang W and Hunter T  (1997) Identification and characterization of a human protein kinase related to budding yeast Cdc7p. Proc Natl Acad Sci U S A 94(26):14320-5
32) Hess GF, et al.  (1998) A human homolog of the yeast CDC7 gene is overexpressed in some tumors and transformed cell lines. Gene 211(1):133-40
33) Roberts BT, et al.  (1999) DNA replication in vertebrates requires a homolog of the Cdc7 protein kinase. Proc Natl Acad Sci U S A 96(6):2800-4