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PMID: 2674650 Published · ppublish English Comparative Study Journal Article Research Support, Non-U.S. Gov't

Molecular cloning and sequence analysis of mutant alleles of the fission yeast cdc2 protein kinase gene: implications for cdc2+ protein structure and function.

Molecular & general genetics : MGG ·Vol. 218 ·No. 1 ·1989-07-00 ·Pages 41-9

Carr AM, MacNeill SA, Hayles J, Nurse P

Abstract

The cdc2+ gene function plays a central role in the control of the mitotic cell cycle of the fission yeast Schizosaccharomyces pombe. Recessive temperature-sensitive mutations in the cdc2 gene cause cell cycle arrest when shifted to the restrictive temperature, while a second class of mutations within the cdc2 gene causes a premature advancement into mitosis. Previously the cdc2+ gene has been cloned and has been shown to encode a 34 kDa phosphoprotein with in vitro protein kinase activity. Here we describe the cloning of 11 mutant alleles of the cdc2 gene using two simple methods, one of which is presented here for the first time. We have sequenced these alleles and find a variety of single amino acid substitutions mapping throughout the cdc2 protein. Analysis of these mutations has identified a number of regions within the cdc2 protein that are important for cdc2+ activity and regulation. These include regions which may be involved in the interaction of the cdc2+ gene product with the proteins encoded by the wee1+, cdc13+ and suc1+ genes.

MeSH Terms
Alleles Amino Acid Sequence Base Sequence Blotting, Southern CDC2 Protein Kinase Cell Division Chromosome Mapping Cloning, Molecular Gene Expression Regulation Genes, Fungal Humans Mutation Phosphoproteins/genetics Plasmids Protein Conformation Protein Kinases/genetics Restriction Mapping Saccharomycetales/genetics Schizosaccharomyces/enzymology,genetics,physiology Sequence Homology, Nucleic Acid Temperature Transformation, Genetic
Chemicals
Phosphoproteins Protein Kinases CDC2 Protein Kinase
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Carr A M
Department of Biochemistry, University of Oxford, UK.
MacNeill S A
Hayles J
Nurse P
References (51)
51 references, click to expand
  1. DNA topoisomerase II is required for condensation and separation of mitotic chromosomes in S. pombe.
    Cell. 1987 Sep 11;50(6):917-25 PMID: 3040264
  2. Identification of p34 and p13, human homologs of the cell cycle regulators of fission yeast encoded by cdc2+ and suc1+.
    Cell. 1987 Jul 17;50(2):319-25 PMID: 3297353
  3. Negative regulation of mitosis by wee1+, a gene encoding a protein kinase homolog.
    Cell. 1987 May 22;49(4):559-67 PMID: 3032459
  4. The genetic fine structure of nonsense suppressors in Schizosaccharomyces pombe : I. sup3 and sup9.
    Curr Genet. 1979 Dec;1(1):45-61 PMID: 24190807
  5. Regulated expression and phosphorylation of a possible mammalian cell-cycle control protein.
    Nature. 1988 Jun 16;333(6174):676-9 PMID: 3287181
  6. Functionally homologous cell cycle control genes in budding and fission yeast.
    Nature. 1982 Dec 23;300(5894):706-9 PMID: 6757758
  7. Site-specific mutagenesis of cdc2+, a cell cycle control gene of the fission yeast Schizosaccharomyces pombe.
    Mol Cell Biol. 1986 Oct;6(10):3523-30 PMID: 3796591
  8. Isolation of cell size mutants of a fission yeast by a new selective method: characterization of mutants and implications for division control mechanisms.
    J Bacteriol. 1981 May;146(2):746-54 PMID: 7217015
  9. Complementation used to clone a human homologue of the fission yeast cell cycle control gene cdc2.
    Nature. 1987 May 7-13;327(6117):31-5 PMID: 3553962
  10. Mutants altered in the control co-ordinating cell division with cell growth in the fission yeast Schizosaccharomyces pombe.
    Mol Gen Genet. 1978 May 3;161(2):215-20 PMID: 672898
  11. Sequence analysis of temperature-sensitive mutations in the Saccharomyces cerevisiae gene CDC28.
    Mol Cell Biol. 1986 Nov;6(11):4099-103 PMID: 3540606
  12. Transcription of the cdc2 cell cycle control gene of the fission yeast Schizosaccharomyces pombe.
    EMBO J. 1986 Feb;5(2):369-73 PMID: 16453669
  13. Sequence of the cell division gene CDC2 from Schizosaccharomyces pombe; patterns of splicing and homology to protein kinases.
    Gene. 1984 Nov;31(1-3):129-34 PMID: 6526270
  14. High-frequency transformation of the fission yeast Schizosaccharomyces pombe.
    Nature. 1981 Mar 12;290(5802):140-2 PMID: 22442847
  15. Enzymology of the pigmented adenine-requiring mutants of Saccharomyces and Schizosaccharomyces.
    Biochem Biophys Res Commun. 1969 Feb 7;34(3):306-10 PMID: 5767025
  16. 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
  17. The fission yeast cell cycle control gene cdc2: isolation of a sequence suc1 that suppresses cdc2 mutant function.
    Mol Gen Genet. 1986 Feb;202(2):291-3 PMID: 3010051
  18. Interaction between cdc13+ and cdc2+ in the control of mitosis in fission yeast; dissociation of the G1 and G2 roles of the cdc2+ protein kinase.
    EMBO J. 1987 Nov;6(11):3441-7 PMID: 3428262
  19. Cyclin in fission yeast.
    Cell. 1988 Sep 9;54(6):738-40 PMID: 2900688
  20. Saccharomyces cerevisiae cell cycle.
    Bacteriol Rev. 1974 Jun;38(2):164-98 PMID: 4599449
  21. A bifunctional gene product involved in two phases of the yeast cell cycle.
    Nature. 1982 Jul 22;298(5872):391-3 PMID: 7045699
  22. Nonsense suppression in Schizosaccharomyces pombe: the S. pombe Sup3-e tRNASerUGA gene is active in S. cerevisiae.
    Mol Gen Genet. 1982;188(2):219-24 PMID: 6818425
  23. Activation at M-phase of a protein kinase encoded by a starfish homologue of the cell cycle control gene cdc2+.
    Nature. 1988 Sep 15;335(6187):251-4 PMID: 3412486
  24. Genetic engineering of Schizosaccharomyces pombe: a system for gene disruption and replacement using the ura4 gene as a selectable marker.
    Mol Gen Genet. 1988 Dec;215(1):81-6 PMID: 3241624
  25. 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
  26. A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity.
    Anal Biochem. 1983 Jul 1;132(1):6-13 PMID: 6312838
  27. Analysis of the accuracy and implications of simple methods for predicting the secondary structure of globular proteins.
    J Mol Biol. 1978 Mar 25;120(1):97-120 PMID: 642007
  28. Suppressors in yeast.
    Curr Top Microbiol Immunol. 1974;64(0):1-47 PMID: 4602646
  29. The protein kinase family: conserved features and deduced phylogeny of the catalytic domains.
    Science. 1988 Jul 1;241(4861):42-52 PMID: 3291115
  30. DNA sequencing with chain-terminating inhibitors.
    Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463-7 PMID: 271968
  31. The NDA3 gene of fission yeast encodes beta-tubulin: a cold-sensitive nda3 mutation reversibly blocks spindle formation and chromosome movement in mitosis.
    Cell. 1984 Dec;39(2 Pt 1):349-58 PMID: 6094012
  32. One-step gene disruption in yeast.
    Methods Enzymol. 1983;101:202-11 PMID: 6310324
  33. The Xenopus cdc2 protein is a component of MPF, a cytoplasmic regulator of mitosis.
    Cell. 1988 Jul 29;54(3):423-31 PMID: 3293802
  34. Primary structure homology between the product of yeast cell division control gene CDC28 and vertebrate oncogenes.
    Nature. 1984 Jan 12-18;307(5947):183-5 PMID: 6361575
  35. Cloning, sequencing and transcriptional control of the Schizosaccharomyces pombe cdc10 'start' gene.
    EMBO J. 1985 Feb;4(2):457-63 PMID: 4018034
  36. Purified maturation-promoting factor contains the product of a Xenopus homolog of the fission yeast cell cycle control gene cdc2+.
    Cell. 1988 Jul 29;54(3):433-9 PMID: 3293803
  37. Gene required in G1 for commitment to cell cycle and in G2 for control of mitosis in fission yeast.
    Nature. 1981 Aug 6;292(5823):558-60 PMID: 7254352
  38. p13suc1 acts in the fission yeast cell division cycle as a component of the p34cdc2 protein kinase.
    EMBO J. 1987 Nov;6(11):3507-14 PMID: 3322810
  39. Regulatory genes controlling mitosis in the fission yeast Schizosaccharomyces pombe.
    Genetics. 1980 Nov;96(3):627-37 PMID: 7262540
  40. suc1 is an essential gene involved in both the cell cycle and growth in fission yeast.
    EMBO J. 1986 Dec 1;5(12):3373-9 PMID: 16453733
  41. The cell cycle control gene cdc2+ of fission yeast encodes a protein kinase potentially regulated by phosphorylation.
    Cell. 1986 Apr 25;45(2):261-8 PMID: 3516412
  42. Programmed gene rearrangements altering gene expression.
    Science. 1987 Feb 6;235(4789):658-67 PMID: 3544215
  43. Genetic applications of yeast transformation with linear and gapped plasmids.
    Methods Enzymol. 1983;101:228-45 PMID: 6310326
  44. Activation of cdc2 protein kinase during mitosis in human cells: cell cycle-dependent phosphorylation and subunit rearrangement.
    Cell. 1988 Jul 1;54(1):17-26 PMID: 3289755
  45. Epistatic gene interactions in the control of division in fission yeast.
    Nature. 1979 May 31;279(5712):428-30 PMID: 16068179
  46. Amino acid alterations within a highly conserved region of the Rous sarcoma virus src gene product pp60src inactivate tyrosine protein kinase activity.
    Mol Cell Biol. 1984 May;4(5):862-6 PMID: 6328273
  47. Cloning and expression of the OMP decarboxylase gene URA4 from Schizosaccharomyces pombe.
    Curr Genet. 1987;12(7):527-34 PMID: 2834100
  48. Genetic nomenclature and gene list of the fission yeast Schizosaccharomyces pombe.
    Curr Genet. 1987;11(8):575-89 PMID: 3329975
  49. cdc25+ functions as an inducer in the mitotic control of fission yeast.
    Cell. 1986 Apr 11;45(1):145-53 PMID: 3955656
  50. Genetic control of the cell division cycle in the fission yeast Schizosaccharomyces pombe.
    Mol Gen Genet. 1976 Jul 23;146(2):167-78 PMID: 958201
  51. PHO85, a negative regulator of the PHO system, is a homolog of the protein kinase gene, CDC28, of Saccharomyces cerevisiae.
    Mol Gen Genet. 1988 Sep;214(1):162-4 PMID: 3067079
Article Info
Journal
Molecular & general genetics : MGG
Abbr.
Mol Gen Genet
ISSN
0026-8925
Published
1989-07-00
Pages
41-9
Language
English
Region
Germany
NLM ID
0125036
Subset
IM
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