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PMID: 10330168 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Cell cycle regulation of DNA replication initiator factor Dbf4p.

Molecular and cellular biology ·Vol. 19 ·No. 6 ·1999-06-00 ·Pages 4270-8

Cheng L, Collyer T, Hardy CF

Abstract

The precise duplication of eukaryotic genetic material takes place once and only once per cell cycle and is dependent on the completion of the previous mitosis. Two evolutionarily conserved kinases, the cyclin B (Clb)/cyclin-dependent kinase (Cdk/Cdc28p) and Cdc7p along with its interacting factor Dbf4p, are required late in G1 to initiate DNA replication. We have determined that the levels of Dbf4p are cell cycle regulated. Dbf4p levels increase as cells begin S phase and remain high through late mitosis, after which they decline dramatically as cells begin the next cell cycle. We report that Dbf4p levels are sensitive to mutations in key components of the anaphase-promoting complex (APC). In addition, Dbf4p is modified in response to DNA damage, and this modification is dependent upon the DNA damage response pathway. We had previously shown that Dbf4p interacts with the M phase polo-like kinase Cdc5p, a key regulator of the APC late in mitosis. These results further link the actions of the initiator protein, Dbf4p, to the completion of mitosis and suggest possible roles for Dbf4p during progression through mitosis.

MeSH Terms
Aldehyde Oxidoreductases/metabolism Cell Cycle/physiology Cell Cycle Proteins/physiology Cyclin B/metabolism DNA Primers Flow Cytometry Fluorescent Antibody Technique Fungal Proteins/metabolism,physiology G1 Phase Glutamate-5-Semialdehyde Dehydrogenase Intracellular Signaling Peptides and Proteins Mitosis Nucleic Acid Synthesis Inhibitors Precipitin Tests Protein Serine-Threonine Kinases RNA-Binding Proteins S Phase Saccharomyces cerevisiae/physiology Saccharomyces cerevisiae Proteins Time Factors
Chemicals
CEF1 protein, S cerevisiae Cell Cycle Proteins Cyclin B DNA Primers Dbf4 protein, S cerevisiae Fungal Proteins Intracellular Signaling Peptides and Proteins Nucleic Acid Synthesis Inhibitors RNA-Binding Proteins Saccharomyces cerevisiae Proteins Aldehyde Oxidoreductases Glutamate-5-Semialdehyde Dehydrogenase MEC1 protein, S cerevisiae Protein Serine-Threonine Kinases
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Cheng L
Department of Cell Biology and Physiology and Department of Genetics, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Collyer T
Hardy C F
References (45)
45 references, click to expand
  1. Cell cycle checkpoints: preventing an identity crisis.
    Science. 1996 Dec 6;274(5293):1664-72 PMID: 8939848
  2. Cell cycle control of DNA replication.
    Science. 1996 Dec 6;274(5293):1659-64 PMID: 8939847
  3. Anaphase initiation in Saccharomyces cerevisiae is controlled by the APC-dependent degradation of the anaphase inhibitor Pds1p.
    Genes Dev. 1996 Dec 15;10(24):3081-93 PMID: 8985178
  4. APC-mediated proteolysis of Ase1 and the morphogenesis of the mitotic spindle.
    Science. 1997 Feb 28;275(5304):1311-4 PMID: 9036857
  5. mcm5/cdc46-bob1 bypasses the requirement for the S phase activator Cdc7p.
    Proc Natl Acad Sci U S A. 1997 Apr 1;94(7):3151-5 PMID: 9096361
  6. Cdc6p-dependent loading of Mcm proteins onto pre-replicative chromatin in budding yeast.
    Proc Natl Acad Sci U S A. 1997 May 27;94(11):5611-6 PMID: 9159120
  7. Loading of an Mcm protein onto DNA replication origins is regulated by Cdc6p and CDKs.
    Cell. 1997 Aug 22;90(4):649-60 PMID: 9288745
  8. CDC5 and CKII control adaptation to the yeast DNA damage checkpoint.
    Cell. 1997 Sep 19;90(6):1097-106 PMID: 9323137
  9. Components and dynamics of DNA replication complexes in S. cerevisiae: redistribution of MCM proteins and Cdc45p during S phase.
    Cell. 1997 Oct 3;91(1):59-69 PMID: 9335335
  10. CDC20 and CDH1: a family of substrate-specific activators of APC-dependent proteolysis.
    Science. 1997 Oct 17;278(5337):460-3 PMID: 9334304
  11. Mcm2 is a target of regulation by Cdc7-Dbf4 during the initiation of DNA synthesis.
    Genes Dev. 1997 Dec 15;11(24):3365-74 PMID: 9407029
  12. Persistent initiation of DNA replication and chromatin-bound MCM proteins during the cell cycle in cdc6 mutants.
    Genes Dev. 1997 Dec 15;11(24):3375-86 PMID: 9407030
  13. Initiation of DNA replication in eukaryotic cells.
    Annu Rev Cell Dev Biol. 1997;13:293-332 PMID: 9442876
  14. The Cdc7 protein kinase is required for origin firing during S phase.
    Genes Dev. 1998 Feb 15;12(4):480-90 PMID: 9472017
  15. Cdc7 is required throughout the yeast S phase to activate replication origins.
    Genes Dev. 1998 Feb 15;12(4):491-501 PMID: 9472018
  16. The Polo-like kinase Cdc5p and the WD-repeat protein Cdc20p/fizzy are regulators and substrates of the anaphase promoting complex in Saccharomyces cerevisiae.
    EMBO J. 1998 Mar 2;17(5):1336-49 PMID: 9482731
  17. The Polo-related kinase Cdc5 activates and is destroyed by the mitotic cyclin destruction machinery in S. cerevisiae.
    Curr Biol. 1998 Apr 23;8(9):497-507 PMID: 9560342
  18. Cell cycle regulation of the Saccharomyces cerevisiae polo-like kinase cdc5p.
    Mol Cell Biol. 1998 Dec;18(12):7360-70 PMID: 9819423
  19. Sequential gene function in the initiation of Saccharomyces cerevisiae DNA synthesis.
    J Mol Biol. 1974 Apr 15;84(3):445-61 PMID: 4618856
  20. Eucaryotic DNA: organization of the genome for replication.
    Cell. 1978 Oct;15(2):317-25 PMID: 719745
  21. A further two mutants defective in initiation of the S phase in the yeast Saccharomyces cerevisiae.
    Mol Gen Genet. 1982;186(3):445-8 PMID: 6750323
  22. Transformation of intact yeast cells treated with alkali cations.
    J Bacteriol. 1983 Jan;153(1):163-8 PMID: 6336730
  23. Complete sequence of the staphylococcal gene encoding protein A. A gene evolved through multiple duplications.
    J Biol Chem. 1984 Feb 10;259(3):1695-702 PMID: 6319407
  24. Functions of microtubules in the Saccharomyces cerevisiae cell cycle.
    J Cell Biol. 1988 Oct;107(4):1409-26 PMID: 3049620
  25. The yeast gene, DBF4, essential for entry into S phase is cell cycle regulated.
    Exp Cell Res. 1989 Feb;180(2):419-28 PMID: 2644125
  26. Activation of replication origins within yeast chromosomes.
    Annu Rev Cell Biol. 1991;7:375-402 PMID: 1809350
  27. Temperature-sensitive cdc7 mutations of Saccharomyces cerevisiae are suppressed by the DBF4 gene, which is required for the G1/S cell cycle transition.
    Genetics. 1992 May;131(1):21-9 PMID: 1592236
  28. CLB5: a novel B cyclin from budding yeast with a role in S phase.
    Genes Dev. 1992 Sep;6(9):1695-706 PMID: 1387626
  29. A question of time: replication origins of eukaryotic chromosomes.
    Cell. 1992 Oct 30;71(3):363-6 PMID: 1423601
  30. A new family of yeast nuclear pore complex proteins.
    J Cell Biol. 1992 Nov;119(4):705-23 PMID: 1385442
  31. Mitotic arrest caused by the amino terminus of Xenopus cyclin B2.
    Mol Cell Biol. 1993 Mar;13(3):1480-8 PMID: 8382770
  32. Cell cycle regulation of the yeast Cdc7 protein kinase by association with the Dbf4 protein.
    Mol Cell Biol. 1993 May;13(5):2899-908 PMID: 8474449
  33. Destruction of the CDC28/CLB mitotic kinase is not required for the metaphase to anaphase transition in budding yeast.
    EMBO J. 1993 May;12(5):1969-78 PMID: 8491189
  34. Full activation of p34CDC28 histone H1 kinase activity is unable to promote entry into mitosis in checkpoint-arrested cells of the yeast Saccharomyces cerevisiae.
    Mol Cell Biol. 1993 Jun;13(6):3744-55 PMID: 8388545
  35. Anaphase is initiated by proteolysis rather than by the inactivation of maturation-promoting factor.
    Cell. 1993 Jul 2;73(7):1393-402 PMID: 8391932
  36. Closing the cell cycle circle in yeast: G2 cyclin proteolysis initiated at mitosis persists until the activation of G1 cyclins in the next cycle.
    Cell. 1994 Jul 1;77(7):1037-50 PMID: 8020094
  37. Interaction of Dbf4, the Cdc7 protein kinase regulatory subunit, with yeast replication origins in vivo.
    Science. 1994 Aug 26;265(5176):1243-6 PMID: 8066465
  38. A 20S complex containing CDC27 and CDC16 catalyzes the mitosis-specific conjugation of ubiquitin to cyclin B.
    Cell. 1995 Apr 21;81(2):279-88 PMID: 7736580
  39. The cyclosome, a large complex containing cyclin-selective ubiquitin ligase activity, targets cyclins for destruction at the end of mitosis.
    Mol Biol Cell. 1995 Feb;6(2):185-97 PMID: 7787245
  40. Two novel related yeast nucleoporins Nup170p and Nup157p: complementation with the vertebrate homologue Nup155p and functional interactions with the yeast nuclear pore-membrane protein Pom152p.
    J Cell Biol. 1995 Dec;131(5):1133-48 PMID: 8522578
  41. An essential role for the Cdc6 protein in forming the pre-replicative complexes of budding yeast.
    Nature. 1996 Jan 11;379(6561):180-2 PMID: 8538771
  42. Cut2 proteolysis required for sister-chromatid seperation in fission yeast.
    Nature. 1996 May 30;381(6581):438-41 PMID: 8632802
  43. TPR proteins required for anaphase progression mediate ubiquitination of mitotic B-type cyclins in yeast.
    Mol Biol Cell. 1996 May;7(5):791-801 PMID: 8744951
  44. How proteolysis drives the cell cycle.
    Science. 1996 Dec 6;274(5293):1652-9 PMID: 8939846
  45. A novel role for Cdc5p in DNA replication.
    Mol Cell Biol. 1996 Dec;16(12):6775-82 PMID: 8943332
Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/MCB.19.6.4270
Published
1999-06-00
Pages
4270-8
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC104387
Subset
IM
Grants
NIGMS NIH HHS · GM5678801 · United States
External Links
PubMed source DOI: 10.1128/MCB.19.6.4270 PMC Full Text View journal details
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