DBF4/YDR052C Summary Help

Standard Name DBF4
Systematic Name YDR052C
Alias LSD7 , DNA52 1
Feature Type ORF, Verified
Description Regulatory subunit of Cdc7p-Dbf4p kinase complex; required for Cdc7p kinase activity and initiation of DNA replication; phosphorylates the Mcm2-7 family of proteins; cell cycle regulated; relative distribution to the nucleus increases upon DNA replication stress (2, 3, 4 and see Summary Paragraph)
Name Description DumbBell Forming 5
Chromosomal Location
ChrIV:560625 to 558511 | ORF Map | GBrowse
Note: this feature is encoded on the Crick strand.
Gbrowse
Gene Ontology Annotations All DBF4 GO evidence and references
  View Computational GO annotations for DBF4
Molecular Function
Manually curated
Biological Process
Manually curated
Cellular Component
Manually curated
High-throughput
Mutant phenotypes All DBF4 Phenotype evidence and references
Classical genetics
conditional
null
Large-scale survey
conditional
null
reduction of function
repressible
Resources
interactions All DBF4 Interaction evidence and references
219 total interaction(s) for 127 unique genes/features.
Physical Interactions
  • Affinity Capture-MS: 9
  • Affinity Capture-RNA: 1
  • Affinity Capture-Western: 13
  • Biochemical Activity: 5
  • Co-localization: 1
  • Co-purification: 2
  • Protein-peptide: 1
  • Protein-RNA: 1
  • Reconstituted Complex: 11
  • Two-hybrid: 27
Genetic Interactions
  • Dosage Growth Defect: 10
  • Dosage Lethality: 5
  • Dosage Rescue: 5
  • Negative Genetic: 56
  • Phenotypic Enhancement: 9
  • Phenotypic Suppression: 3
  • Positive Genetic: 2
  • Synthetic Growth Defect: 38
  • Synthetic Lethality: 11
  • Synthetic Rescue: 9
Resources
Expression Summary
histogram
Resources
Protein Information All DBF4 Protein evidence and references
Localization
Phosphorylation PhosphoGRID | PhosphoPep Database
Structure
Homologs
sequence information
ChrIV:560625 to 558511 | ORF Map | GBrowse
Note: this feature is encoded on the Crick strand.
SGD ORF map
Last Update Coordinates: 2011-02-03 | Sequence: 1996-07-31
Subfeature details
Relative
Coordinates		 Chromosomal
Coordinates		 Most Recent Updates
Coordinates Sequence
CDS 1..2115 560625..558511 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 | Entrez Gene | Entrez RefSeq Protein | MIPS | Search all NCBI (Entrez) | UniProtKB
Primary SGDIDS000002459
SUMMARY PARAGRAPH for DBF4

DBF4 is an essential gene that is expressed in a cell cycle-dependent manner (reviewed in 6, 7, 8, 9, 10, 11, 12). It encodes the regulatory subunit for the protein kinase Cdc7p; the activity of the Cdc7p-Dbf4p complex is required throughout S phase for the initiation of DNA synthesis at replication origins. The function of the Cdc7p-Dbf4p complex is analogous to that of cyclin-CDK complexes; here, Cdc7p is the catalytic subunit and is activated by association with Dbf4p during late G1 (13, 14).

The Cdc7p-Dbf4p complex interacts physically with replication origins: Cdc7p interacts with Orc2p (15), and Dbf4p interacts with origin DNA (16). Dbf4p interacts with replication origins and with Cdc7p through different domains; both domains are essential for its function (16).

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 (3). Further, a mutation in MCM5/CDC46 can bypass the requirement for Cdc7p kinase activity in initiating DNA synthesis (13, 17). Results of two-hybrid and GST-Mcm2 fusion affinity column chromatography showed that Cdc7p and Dbf4p interact physically with Mcm2p 3.

A homolog of Dbf4p has been identified in S. pombe (18), and homologs of Cdc7p have been found in S. pombe (19, 18), Xenopus, and human (20, 21); evidence suggests that the homologs may perform the same function as the S. cerevisiae proteins.

Last updated: 1999-04-13

References cited on this page View Complete Literature Guide for DBF4
1) Dumas LB, et al.  (1982) New temperature-sensitive mutants of Saccharomyces cerevisiae affecting DNA replication. Mol Gen Genet 187(1):42-6
2) Cheng L, et al.  (1999) Cell cycle regulation of DNA replication initiator factor Dbf4p. Mol Cell Biol 19(6):4270-8
3) 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
4) Tkach JM, et al.  (2012) Dissecting DNA damage response pathways by analysing protein localization and abundance changes during DNA replication stress. Nat Cell Biol 14(9):966-76
5) Johnston LH and Thomas AP  (1982) The isolation of new DNA synthesis mutants in the yeast Saccharomyces cerevisiae. Mol Gen Genet 186(3):439-44
6) Leatherwood J  (1998) Emerging mechanisms of eukaryotic DNA replication initiation. Curr Opin Cell Biol 10(6):742-8
7) Dutta A and Bell SP  (1997) Initiation of DNA replication in eukaryotic cells. Annu Rev Cell Dev Biol 13():293-332
8) Toone WM, et al.  (1997) Getting started: regulating the initiation of DNA replication in yeast. Annu Rev Microbiol 51:125-49
9) Stillman B  (1996) Cell cycle control of DNA replication. Science 274(5293):1659-64
10) 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
11) Sclafani RA and Jackson AL  (1994) Cdc7 protein kinase for DNA metabolism comes of age. Mol Microbiol 11(5):805-10
12) Sherlock G and Rosamond J  (1993) Starting to cycle: G1 controls regulating cell division in budding yeast. J Gen Microbiol 139(11):2531-41
13) 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
14) 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
15) Hardy CF  (1996) Characterization of an essential Orc2p-associated factor that plays a role in DNA replication. Mol Cell Biol 16(4):1832-41
16) 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
17) 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
18) Brown GW and Kelly TJ  (1998) Purification of Hsk1, a minichromosome maintenance protein kinase from fission yeast. J Biol Chem 273(34):22083-90
19) 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
20) 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
21) 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