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
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
High-throughput
Regulators 123 genes
Resources
Classical genetics
conditional
Large-scale survey
conditional
null
overexpression
reduction of function
repressible
Resources
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

Resources
Expression Summary
histogram
Resources
Length (a.a.) 513
Molecular Weight (Da) 58,036
Isoelectric Point (pI) 10.23
Localization
Phosphorylation PhosphoGRID | PhosphoPep Database
Structure
Homologs
sequence information
ChrX:69338 to 70879 | ORF Map | GBrowse
SGD ORF map
Genetic position: -124 cM
Last Update Coordinates: 2011-02-03 | Sequence: 1996-07-31
Subfeature details
Relative
Coordinates
Chromosomal
Coordinates
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
Resources
External Links All Associated Seq | Entrez Gene | Entrez RefSeq Protein | MIPS | Search all NCBI (Entrez) | UniProtKB
Primary SGDIDS000003730
SUMMARY PARAGRAPH for CDC6

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