CDC6/YJL194W Summary Help

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; relocalizes from nucleus to cytoplasm upon DNA replication stress (2, 3 and see Summary Paragraph)
Name Description Cell Division Cycle 4
Chromosomal Location
ChrX:69338 to 70879 | ORF Map | GBrowse
Genetic position: -124 cM
Gene Ontology 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
Regulators 123 genes
Classical genetics
Large-scale survey
reduction of function
214 total interaction(s) for 122 unique genes/features.
Physical Interactions
  • Affinity Capture-MS: 7
  • Affinity Capture-RNA: 2
  • Affinity Capture-Western: 25
  • Biochemical Activity: 9
  • Co-localization: 5
  • Protein-peptide: 1
  • Protein-RNA: 1
  • Reconstituted Complex: 14
  • Two-hybrid: 20

Genetic Interactions
  • Dosage Growth Defect: 2
  • Dosage Lethality: 10
  • Dosage Rescue: 11
  • Negative Genetic: 23
  • Phenotypic Enhancement: 3
  • Phenotypic Suppression: 4
  • Synthetic Growth Defect: 36
  • Synthetic Lethality: 30
  • Synthetic Rescue: 11

Expression Summary
Length (a.a.) 513
Molecular Weight (Da) 58,036
Isoelectric Point (pI) 10.23
Phosphorylation PhosphoGRID | PhosphoPep Database
sequence information
ChrX:69338 to 70879 | ORF Map | GBrowse
Genetic position: -124 cM
Last Update Coordinates: 2011-02-03 | Sequence: 1996-07-31
Subfeature details
Most Recent Updates
Coordinates Sequence
CDS 1..1542 69338..70879 2011-02-03 1996-07-31
Retrieve sequences
Analyze Sequence
S288C only
S288C vs. other species
S288C vs. other strains
External Links All Associated Seq | Entrez Gene | Entrez RefSeq Protein | MIPS | Search all NCBI (Entrez) | UniProtKB
Primary SGDIDS000003730

Cdc6p is an unstable protein (5) that is required for the assembly and maintenance of the pre-replicative complex (pre-RC) (5, 6, 7). 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 (8, 9, 10, 6, 11). In pre-RC formation, Cdc6p acts as a loading factor for the Mcm2-7 proteins (encoded by MCM2, MCM3, CDC54, CDC46, MCM6, and CDC47)(8). 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 (12, 13, 5). Transcriptional repression of CDC6 prevents both pre-RC formation and initiation of DNA synthesis. cdc6 temperature-sensitive mutants are defective in replication initiation (14, 15); established pre-RCs are thermolabile in a cdc6 temperature-sensitive mutant. Cdc6p must be present before late G1 to permit pre-RC formation (16). Cdc6p homologs are required for DNA replication early in S phase in S. pombe (Cdc18; 17) and Xenopus (18). 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 (19). 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 (19, 20) .

Last updated: 1999-03-03 Contact SGD

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) 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
4) 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
5) 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
6) 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
7) 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
8) Leatherwood J  (1998) Emerging mechanisms of eukaryotic DNA replication initiation. Curr Opin Cell Biol 10(6):742-8
9) Dutta A and Bell SP  (1997) Initiation of DNA replication in eukaryotic cells. Annu Rev Cell Dev Biol 13():293-332
10) 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
11) Diffley JF, et al.  (1994) Two steps in the assembly of complexes at yeast replication origins in vivo. Cell 78(2):303-16
12) 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
13) 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
14) 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
15) 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
16) 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
17) 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
18) 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
19) 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
20) 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