Home LiteratureArticle Details
PMID: 1600944 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. Research Support, U.S. Gov't, P.H.S.

Dual functions of CDC6: a yeast protein required for DNA replication also inhibits nuclear division.

The EMBO journal ·Vol. 11 ·No. 6 ·1992-06-00 ·Pages 2167-76

Bueno A, Russell P

Abstract

The Saccharomyces cerevisiae gene CDC6, whose protein product is required for DNA replication, is transcribed only in late G1 and S phases. We have discovered a critical reason why CDC6 expression is regulated in this fashion. Constitutive CDC6 transcription greatly delayed the initiation of M phase without effecting the G1-S transition or growth rate. This occurred in both fission and budding yeasts. The CDC6-induced M phase delay was dependent on the wee1/mik1 mitotic inhibitor kinases and was greatly accentuated in strains defective for the cdc25/MIH1 mitotic inducer phosphatases, indicating that CDC6 indirectly inhibits activation of the p34cdc2/CDC28 M phase kinase. Thus CDC6 appears to have an important and perhaps unique dual role in S phase, it is first required for the initiation of DNA replication and then actively participates in the suppression of nuclear division.

Related Genes
CDC6 MIH1
MeSH Terms
Base Sequence Cell Cycle/drug effects,genetics Cell Cycle Proteins Cell Division Cell Nucleus/physiology,ultrastructure DNA Replication/genetics Fungal Proteins/genetics,metabolism Genes, Fungal Mating Factor Mitosis/genetics Molecular Sequence Data Oligodeoxyribonucleotides Peptides/pharmacology Pheromones/pharmacology Plasmids Protein Tyrosine Phosphatases/genetics,metabolism Saccharomyces cerevisiae/cytology,genetics,physiology Saccharomyces cerevisiae Proteins Transcription, Genetic ras-GRF1
Chemicals
CDC6 protein, S cerevisiae Cell Cycle Proteins Fungal Proteins Oligodeoxyribonucleotides Peptides Pheromones Saccharomyces cerevisiae Proteins ras-GRF1 Mating Factor Protein Tyrosine Phosphatases
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Bueno A
Department of Molecular and Cell Biology, Scripps Research Institute, La Jolla, CA 92037.
Russell P
References (47)
47 references, click to expand
  1. Epistatic gene interactions in the control of division in fission yeast.
    Nature. 1979 May 31;279(5712):428-30 PMID: 16068179
  2. Involvement of cdc13+ in mitotic control in Schizosaccharomyces pombe: possible interaction of the gene product with microtubules.
    EMBO J. 1988 Aug;7(8):2321-7 PMID: 2847913
  3. Cyclin promotes the tyrosine phosphorylation of p34cdc2 in a wee1+ dependent manner.
    EMBO J. 1991 May;10(5):1255-63 PMID: 1850698
  4. mik1 and wee1 cooperate in the inhibitory tyrosine phosphorylation of cdc2.
    Cell. 1991 Mar 22;64(6):1111-22 PMID: 1706223
  5. cdc25+ functions as an inducer in the mitotic control of fission yeast.
    Cell. 1986 Apr 11;45(1):145-53 PMID: 3955656
  6. A single essential gene, PRI2, encodes the large subunit of DNA primase in Saccharomyces cerevisiae.
    Mol Cell Biol. 1989 Jul;9(7):3081-7 PMID: 2528682
  7. The mitotic inducer nim1+ functions in a regulatory network of protein kinase homologs controlling the initiation of mitosis.
    Cell. 1987 May 22;49(4):569-76 PMID: 3453113
  8. Negative regulation of mitosis by wee1+, a gene encoding a protein kinase homolog.
    Cell. 1987 May 22;49(4):559-67 PMID: 3032459
  9. Transcriptional regulation of the cell cycle-dependent thymidylate synthase gene of Saccharomyces cerevisiae.
    Mol Cell Biol. 1988 Nov;8(11):4616-24 PMID: 3062362
  10. The RAD9 gene controls the cell cycle response to DNA damage in Saccharomyces cerevisiae.
    Science. 1988 Jul 15;241(4863):317-22 PMID: 3291120
  11. DNA polymerase I gene of Saccharomyces cerevisiae: nucleotide sequence, mapping of a temperature-sensitive mutation, and protein homology with other DNA polymerases.
    Proc Natl Acad Sci U S A. 1988 Jun;85(11):3772-6 PMID: 3287376
  12. Checkpoints: controls that ensure the order of cell cycle events.
    Science. 1989 Nov 3;246(4930):629-34 PMID: 2683079
  13. Regulation of p34cdc2 protein kinase during mitosis.
    Cell. 1989 Jul 28;58(2):361-72 PMID: 2665944
  14. Molecular cloning of Saccharomyces cerevisiae CDC6 gene. Isolation, identification, and sequence analysis.
    J Biol Chem. 1989 May 25;264(15):9022-9 PMID: 2656692
  15. Conservation of mitotic controls in fission and budding yeasts.
    Cell. 1989 Apr 21;57(2):295-303 PMID: 2649252
  16. The CDC8 transcript is cell cycle regulated in yeast and is expressed coordinately with CDC9 and CDC21 at a point preceding histone transcription.
    Exp Cell Res. 1987 Jul;171(1):223-31 PMID: 3305044
  17. The yeast DNA polymerase I transcript is regulated in both the mitotic cell cycle and in meiosis and is also induced after DNA damage.
    Nucleic Acids Res. 1987 Jul 10;15(13):5017-30 PMID: 3299263
  18. Human homolog of fission yeast cdc25 mitotic inducer is predominantly expressed in G2.
    Proc Natl Acad Sci U S A. 1990 Jul;87(13):5139-43 PMID: 2195549
  19. Stoichiometry of G protein subunits affects the Saccharomyces cerevisiae mating pheromone signal transduction pathway.
    Mol Cell Biol. 1990 Feb;10(2):510-7 PMID: 2105453
  20. Expression of the yeast DNA primase gene, PRI1, is regulated within the mitotic cell cycle and in meiosis.
    Mol Gen Genet. 1990 Mar;221(1):44-8 PMID: 2183009
  21. Molecular cloning, structure and expression of the yeast proliferating cell nuclear antigen gene.
    Nucleic Acids Res. 1990 Jan 25;18(2):261-5 PMID: 1970160
  22. G1-specific cyclins of S. cerevisiae: cell cycle periodicity, regulation by mating pheromone, and association with the p34CDC28 protein kinase.
    Cell. 1990 Jul 27;62(2):225-37 PMID: 2142620
  23. Universal control mechanism regulating onset of M-phase.
    Nature. 1990 Apr 5;344(6266):503-8 PMID: 2138713
  24. Mutation of fission yeast cell cycle control genes abolishes dependence of mitosis on DNA replication.
    Cell. 1990 Feb 23;60(4):665-73 PMID: 2406029
  25. The structure of transposable yeast mating type loci.
    Cell. 1980 Mar;19(3):753-64 PMID: 6244896
  26. Evolutionary divergence of the mRNA transcription initiation mechanism in yeast.
    Nature. 1983 Jan 13;301(5896):167-9 PMID: 6296690
  27. Isolation of genes by complementation in yeast: molecular cloning of a cell-cycle gene.
    Proc Natl Acad Sci U S A. 1980 Apr;77(4):2119-23 PMID: 6246523
  28. Unidirectional digestion with exonuclease III creates targeted breakpoints for DNA sequencing.
    Gene. 1984 Jun;28(3):351-9 PMID: 6235151
  29. Microbial determinations by flow cytometry.
    J Gen Microbiol. 1979 Aug;113(2):369-75 PMID: 390094
  30. DNA sequencing with chain-terminating inhibitors.
    Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463-7 PMID: 271968
  31. Sequential function of gene products relative to DNA synthesis in the yeast cell cycle.
    J Mol Biol. 1976 Jul 15;104(4):803-17 PMID: 785015
  32. Genetic control of cell size at cell division in yeast.
    Nature. 1975 Aug 14;256(5518):547-51 PMID: 1165770
  33. The cdc25 protein contains an intrinsic phosphatase activity.
    Cell. 1991 Oct 4;67(1):189-96 PMID: 1655274
  34. Isolation of three novel human cyclins by rescue of G1 cyclin (Cln) function in yeast.
    Cell. 1991 Sep 20;66(6):1197-206 PMID: 1833066
  35. The cdc25 protein controls tyrosine dephosphorylation of the cdc2 protein in a cell-free system.
    Cell. 1991 Mar 8;64(5):903-14 PMID: 1825803
  36. Fission yeast p107wee1 mitotic inhibitor is a tyrosine/serine kinase.
    Nature. 1991 Feb 28;349(6312):808-11 PMID: 1825699
  37. Control of gene expression and the yeast cell cycle.
    Crit Rev Eukaryot Gene Expr. 1991;1(3):189-205 PMID: 1802110
  38. p80cdc25 mitotic inducer is the tyrosine phosphatase that activates p34cdc2 kinase in fission yeast.
    EMBO J. 1991 Dec;10(13):4301-9 PMID: 1756737
  39. cdc25 is a specific tyrosine phosphatase that directly activates p34cdc2.
    Cell. 1991 Oct 4;67(1):197-211 PMID: 1913817
  40. A cell cycle-responsive transcriptional control element and a negative control element in the gene encoding DNA polymerase alpha in Saccharomyces cerevisiae.
    Proc Natl Acad Sci U S A. 1991 Jul 15;88(14):6058-62 PMID: 2068085
  41. Molecular genetic analysis of fission yeast Schizosaccharomyces pombe.
    Methods Enzymol. 1991;194:795-823 PMID: 2005825
  42. CDC6 mRNA fluctuates periodically in the yeast cell cycle.
    J Biol Chem. 1990 Nov 15;265(32):19904-9 PMID: 2246267
  43. Characterization of RAD9 of Saccharomyces cerevisiae and evidence that its function acts posttranslationally in cell cycle arrest after DNA damage.
    Mol Cell Biol. 1990 Dec;10(12):6554-64 PMID: 2247073
  44. The fission yeast cdc2/cdc13/suc1 protein kinase: regulation of catalytic activity and nuclear localization.
    Cell. 1989 Aug 11;58(3):485-97 PMID: 2569363
  45. Cloning and sequencing of the cyclin-related cdc13+ gene and a cytological study of its role in fission yeast mitosis.
    J Cell Sci. 1988 Dec;91 ( Pt 4):587-95 PMID: 2908246
  46. Tyrosine phosphorylation of the fission yeast cdc2+ protein kinase regulates entry into mitosis.
    Nature. 1989 Nov 2;342(6245):39-45 PMID: 2682257
  47. Dephosphorylation and activation of a p34cdc2/cyclin B complex in vitro by human CDC25 protein.
    Nature. 1991 May 16;351(6323):242-5 PMID: 1828290
Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
Published
1992-06-00
Pages
2167-76
Language
English
Region
England
NLM ID
8208664
PMCID
PMC556684
Subset
IM
External Links
PubMed source PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2