CDC6/YJL194W Summary Help

CDC6 BASIC INFORMATION

Standard Name CDC6 1
Systematic Name YJL194W
Feature Type ORF, Verified
Description Essential ATP-binding protein required for DNA replication, component of the pre-replicative complex (pre-RC) which requires ORC to associate with chromatin and is in turn required for Mcm2-7p DNA association; homologous to S. pombe Cdc18p (2 and see Summary Paragraph)
Name Description Cell Division Cycle 3
GO Annotations All CDC6 GO evidence and references
    View Computational GO annotations for CDC6
Molecular Function
Manually curated
Biological Process
Manually curated
Cellular Component
Manually curated
Mutant Phenotype All CDC6 Phenotype details and references
Classical genetics
conditional
Large-scale survey
null
repressible
Interactions CDC6 All interactions details and references
135 total interaction(s) for 84 unique genes/features.
Physical Interactions
  • Affinity Capture-MS: 7
  • Affinity Capture-Western: 11
  • Biochemical Activity: 3
  • Co-localization: 5
  • Protein-peptide: 1
  • Protein-RNA: 1
  • Reconstituted Complex: 14
  • Two-hybrid: 14

Genetic Interactions
  • Dosage Lethality: 9
  • Dosage Rescue: 11
  • Phenotypic Enhancement: 4
  • Phenotypic Suppression: 5
  • Synthetic Growth Defect: 13
  • Synthetic Lethality: 32
  • Synthetic Rescue: 5

Sequence Information
ChrX:69337 to 70878 | ORF Map | GBrowse
Gbrowse
Genetic position: -124 cM
Last Update Coordinates: 1996-07-31 | Sequence: 1996-07-31
Subfeature details
Relative
Coordinates
Chromosomal
Coordinates
Most Recent Updates
Coordinates Sequence
CDS 1..1542 69337..70878 1996-07-31 1996-07-31
External Links All Associated Seq | Entrez Gene | Entrez RefSeq Protein | MIPS | UniProtKB
Primary SGDIDS000003730

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Expression Summary histogram

NOMENCLATURE CONFLICT NOTE

NameRelevanceDescription
POL3Nomenclature conflictCDC6/YJL194W encodes an ATPase required for DNA replication and is homologous to pombe cdc18. Do not confuse CDC6/YJL194W with the S. pombe cdc6 gene, which encodes a DNA polymerase delta subunit and is similar to the S. cerevisiae POL3/YDL102W.

SUMMARY PARAGRAPH for CDC6

Cdc6p is an unstable protein (4) that is required for the assembly and maintenance of the pre-replicative complex (pre-RC) (4, 5, 6). The pre-RC is an assembly of proteins that forms at origins of DNA replication between late M phase and the G1/S transition and includes proteins believed to act in DNA replication initiation (7, 8, 9, 5, 10). In pre-RC formation, Cdc6p acts as a loading factor for the Mcm2-7 proteins (encoded by MCM2, MCM3, CDC54, CDC46, MCM6, and CDC47)(7). Both CDC6 mRNA and protein levels peak at the M/G1 transition, when pre-RCs are formed; de novo Cdc6p synthesis is required for each round of DNA replication (11, 12, 4). Transcriptional repression of CDC6 prevents both pre-RC formation and initiation of DNA synthesis. cdc6 temperature-sensitive mutants are defective in replication initiation (13, 14); established pre-RCs are thermolabile in a cdc6 temperature-sensitive mutant. Cdc6p must be present before late G1 to permit pre-RC formation (15). Cdc6p homologs are required for DNA replication early in S phase in S. pombe (Cdc18; 16) and Xenopus (17). Cdc6p and its homologs also show sequence similarity to subunits of eukaryotic and prokaryotic clamp-loaders such as RFC, which load ring-shaped DNA polymerase processivity factors onto DNA (18). All Cdc6p homologues contain a bipartite Walker ATP-binding motif and the phenotypes of mutations in the Walker A motif suggest that nucleotide binding is important for establishing the prereplicative complex at replication origins (18, 19) .

Last updated: 1999-03-03

REFERENCES CITED ON THIS PAGE [View Complete Literature Guide for CDC6]

1) Hilger, F.  (1985) Personal Communication, Mortimer Map Edition 9
2) Bell SP and Dutta A  (2002) DNA replication in eukaryotic cells. Annu Rev Biochem 71():333-74
3) 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
4) Piatti S, et al.  (1995) Cdc6 is an unstable protein whose de novo synthesis in G1 is important for the onset of S phase and for preventing a 'reductional' anaphase in the budding yeast Saccharomyces cerevisiae. EMBO J 14(15):3788-99
5) Cocker JH, et al.  (1996) An essential role for the Cdc6 protein in forming the pre-replicative complexes of budding yeast. Nature 379(6561):180-2
6) Detweiler CS and Li JJ  (1997) Cdc6p establishes and maintains a state of replication competence during G1 phase. J Cell Sci 110 ( Pt 6):753-63
7) Leatherwood J  (1998) Emerging mechanisms of eukaryotic DNA replication initiation. Curr Opin Cell Biol 10(6):742-8
8) Dutta A and Bell SP  (1997) Initiation of DNA replication in eukaryotic cells. Annu Rev Cell Dev Biol 13:293-332
9) Santocanale C and Diffley JF  (1996) ORC- and Cdc6-dependent complexes at active and inactive chromosomal replication origins in Saccharomyces cerevisiae. EMBO J 15(23):6671-9
10) Diffley JF, et al.  (1994) Two steps in the assembly of complexes at yeast replication origins in vivo. Cell 78(2):303-16
11) Bueno A and Russell P  (1992) Dual functions of CDC6: a yeast protein required for DNA replication also inhibits nuclear division. EMBO J 11(6):2167-76
12) Zwerschke W, et al.  (1994) The Saccharomyces cerevisiae CDC6 gene is transcribed at late mitosis and encodes a ATP/GTPase controlling S phase initiation. J Biol Chem 269(37):23351-6
13) Hogan E and Koshland D  (1992) Addition of extra origins of replication to a minichromosome suppresses its mitotic loss in cdc6 and cdc14 mutants of Saccharomyces cerevisiae. Proc Natl Acad Sci U S A 89(7):3098-102
14) Liang C, et al.  (1995) ORC and Cdc6p interact and determine the frequency of initiation of DNA replication in the genome. Cell 81(5):667-76
15) Piatti S, et al.  (1996) Activation of S-phase-promoting CDKs in late G1 defines a "point of no return" after which Cdc6 synthesis cannot promote DNA replication in yeast. Genes Dev 10(12):1516-31
16) Nishitani H and Nurse P  (1995) p65cdc18 plays a major role controlling the initiation of DNA replication in fission yeast. Cell 83(3):397-405
17) Coleman TR, et al.  (1996) The Xenopus Cdc6 protein is essential for the initiation of a single round of DNA replication in cell-free extracts. Cell 87(1):53-63
18) Perkins G and Diffley JF  (1998) Nucleotide-dependent prereplicative complex assembly by Cdc6p, a homolog of eukaryotic and prokaryotic clamp-loaders. Mol Cell 2(1):23-32
19) Weinreich M, et al.  (1999) The Cdc6p nucleotide-binding motif is required for loading mcm proteins onto chromatin. Proc Natl Acad Sci U S A 96(2):441-6