Crossref journal-article
Oxford University Press (OUP)
Genetics (286)
Abstract

Abstract The roles in DNA replication of two distinct protein kinases, Cdc7p/Dbf4p and Cdk1p/Clb (B-type cyclin), were studied. This was accomplished through a genetic and molecular analysis of the mechanism by which the mcm5-bob1 mutation bypasses the function of the Cdc7p/Dbf4p kinase. Genetic experiments revealed that loss of either Clb5p or Clb2p cyclins suppresses the mcm5-bob1 mutation and prevents bypass. These two cyclins have distinct roles in bypass and presumably in DNA replication as overexpression of one could not complement the loss of the other. Furthermore, the ectopic expression of CLB2 in G1 phase cannot substitute for CLB5 function in bypass of Cdc7p/Dbf4p by mcm5-bob1. Molecular experiments revealed that the mcm5-bob1 mutation allows for constitutive loading of Cdc45p at early origins in arrested G1 phase cells when both kinases are inactive. A model is proposed in which the Mcm5-bob1 protein assumes a unique molecular conformation without prior action by either kinase. This conformation allows for stable binding of Cdc45p to the origin. However, DNA replication still cannot occur without the combined action of Cdk1p/Clb5p and Cdk1p/Clb2p. Thus Cdc7p and Cdk1p kinases catalyze the initiation of DNA replication at several distinct steps, of which only a subset is bypassed by the mcm5-bob1 mutation.

Bibliography

Sclafani, R. A., Tecklenburg, M., & Pierce, A. (2002). The mcm5-bob1 Bypass of Cdc7p/Dbf4p in DNA Replication Depends on Both Cdk1-Independent and Cdk1-Dependent Steps in Saccharomyces cerevisiae. Genetics, 161(1), 47–57.

Authors 3
  1. Robert A Sclafani (first)
  2. Marianne Tecklenburg (additional)
  3. Angela Pierce (additional)
References 57 Referenced 31
  1. 10.1093/genetics/116.4.541 / Genetics / A method for gene disruption that allows repeated use of URA3 selection in the construction of multiply disrupted yeast strains by Alani (1987)
  2. 10.1016/S0092-8674(01)80009-X / Cell / Components and dynamics of DNA replication complexes in S. cerevisiae: redistribution of MCM proteins and Cdc45p during the S phase by Aparicio (1997)
  3. 10.1073/pnas.96.16.9130 / Proc. Natl. Acad. Sci. USA / Differential assembly of cdc45p and DNA polymerases at early and late origins of DNA replication by Aparicio (1999)
  4. 10.1128/MCB.15.9.5030 / Mol. Cell. Biol. / Negative regulation of G1 and G2 by S-Phase cyclins of Saccharomyces cerevisiae by Basco (1995)
  5. 10.1101/gad.12.4.480 / Genes Dev. / The Cdc7 protein kinase is required for origin firing during S phase by Bousset (1998)
  6. 10.1128/MCB.19.6.4270 / Mol. Cell. Biol. / Cell cycle regulation of DNA replication initiator factor Dbf4p by Cheng (1999)
  7. {'key': '2022010513521624600_R7', 'first-page': '11', 'article-title': 'Specialization and targeting of B-type cyclins', 'volume': '4', 'author': 'Cross', 'year': '1999', 'journal-title': 'Cell'} / Cell / Specialization and targeting of B-type cyclins by Cross (1999)
  8. 10.1093/embo-reports/kvd108 / EMBO Rep. / The yeast mitotic cyclin Clb2 cannot substitute for S phase cyclins in replication origin firing by Donaldson (2000)
  9. 10.1101/gad.12.4.491 / Genes Dev. / Cdc7 is required throughout the yeast S phase to activate replication origins by Donaldson (1998)
  10. 10.1016/S1097-2765(00)80127-6 / Mol. Cell / CLB5-dependent activation of late replication origins in S. cerevisiae by Donaldson (1998)
  11. 10.1101/gad.6.9.1695 / Genes Dev. / CLB5: a novel B cyclin from budding yeast with a role in S phase by Epstein (1992)
  12. 10.1128/MCB.20.1.242-248.2000 / Mol. Cell. Biol. / Dbf4p, an essential S phase-promoting factor, is targeted for degradation by the anaphase-promoting complex by Ferreira (2000)
  13. 10.1091/mbc.3.7.805 / Mol. Biol. Cell / Characterization of four B-type cyclin genes of the budding yeast Saccharomyces cerevisiae by Fitch (1992)
  14. 10.1074/jbc.M909787199 / J. Biol. Chem. / Premature structural changes at replication origins in a yeast minichromosome maintenance (MCM) mutant by Geraghty (2000)
  15. 10.1016/0092-8674(91)90417-W / Cell / A cyclin B homolog in S. cerevisiae: chronic activation of the Cdc28 protein kinase by cyclin prevents exit from mitosis by Ghiara (1991)
  16. 10.1038/43927 / Nature / Evidence that a free-running oscillator drives G1 events in the budding yeast cell cycle by Haase (1999)
  17. 10.1073/pnas.94.7.3151 / Proc. Natl. Acad. Sci. USA / mcm5/cdc46-bob1 bypasses the requirement for the S phase activator Cdc7p by Hardy (1997)
  18. 10.1128/jb.93.5.1662-1670.1967 / J. Bacteriol. / Macromolecule synthesis in temperature-sensitive mutants of yeast by Hartwell (1967)
  19. 10.1093/genetics/74.2.267 / Genetics / Genetic control of the cell division cycle in yeast: genetic analysis of cdc mutants by Hartwell (1973)
  20. 10.1016/0378-1119(86)90293-3 / Gene / A rapid, efficient method for isolating DNA from yeast by Holm (1986)
  21. 10.1128/jb.153.1.163-168.1983 / J. Bacteriol. / Transformation of intact yeast cells treated with alkali cations by Ito (1983)
  22. {'key': '2022010513521624600_R22', 'first-page': '2899', 'article-title': 'Cell cycle regulation of the yeast Cdc7 protein kinase by association with the Dbf4 protein', 'volume': '13', 'author': 'Jackson', 'year': '1993', 'journal-title': 'Mol. Cell. Biol.'} / Mol. Cell. Biol. / Cell cycle regulation of the yeast Cdc7 protein kinase by association with the Dbf4 protein by Jackson (1993)
  23. 10.1101/gad.14.12.1528 / Genes Dev. / Xenopus Cdc7 function is dependent on licensing but not on XORC, XCdc6, or CDK activity and is required for XCdc45 loading by Jares (2000)
  24. 10.1093/embo-reports/kvd076 / EMBO Rep. / The Cdc7/Dbf4 protein kinase: target of the S phase checkpoint? by Jares (2000)
  25. 10.1016/S0167-4781(98)00033-5 / Biochim. Biophys. Acta / MCM proteins: evolution, properties, and role in DNA replication by Kearsey (1998)
  26. 10.1146/annurev.biochem.69.1.829 / Annu. Rev. Biochem. / Regulation of chromosome replication by Kelly (2000)
  27. 10.1016/S0959-437X(00)00158-1 / Curr. Opin. Genet. Dev. / Is the MCM2-7 complex the eukaryotic DNA replication fork helicase? by Labib (2001)
  28. 10.1242/jcs.114.8.1447 / J. Cell Sci. / Initiating DNA synthesis: from recruiting to activating the MCM complex by Lei (2001)
  29. 10.1016/S1097-2765(00)80347-0 / Mol. Cell / The centromeric sister chromatid cohesion site directs Mcd1p binding to adjacent sequences by Megee (1999)
  30. 10.1101/gad.11.24.3401 / Genes Dev. / Budding yeast centromere composition and assembly as revealed by in vivo cross-linking by Meluh (1997)
  31. 10.1093/emboj/17.19.5699 / EMBO J. / Xenopus Cdc45-dependent loading of DNA polymerase alpha onto chromatin under the control of S-phase cdk by Mimura (1998)
  32. 10.1016/0168-9525(96)10041-X / Trends Genet. / At the heart of the budding yeast cell cycle by Nasmyth (1996)
  33. {'key': '2022010513521624600_R33', 'first-page': '331', 'article-title': 'Control of S phase', 'volume-title': 'DNA Replication in Eukaryotic Cells', 'author': 'Nasmyth', 'year': '1996'} / DNA Replication in Eukaryotic Cells / Control of S phase by Nasmyth (1996)
  34. 10.1038/35082600 / Nature / Cyclin-dependent kinases prevent DNA re-replication through multiple mechanisms by Nguyen (2001)
  35. 10.1128/MCB.20.11.3795-3806.2000 / Mol. Cell. Biol. / Hierarchy of S-phase-promoting factors: yeast Dbf4-cdc7 kinase requires prior S-phase cyclin-dependent kinase activation by Nougarede (2000)
  36. 10.1128/MCB.19.7.4888 / Mol. Cell. Biol. / Cell cycle control of cdc7p kinase activity through regulation of dbf4p stability by Oshiro (1999)
  37. 10.1016/0027-5107(95)00030-M / Mutat. Res. / Cell cycle regulation of induced mutagenesis in yeast by Ostroff (1995)
  38. 10.1073/pnas.94.23.12521 / Proc. Natl. Acad. Sci. USA / CDC45 is required in conjunction with CDC7/DBF4 to trigger the initiation of DNA replication by Owens (1997)
  39. 10.1016/S0955-0674(98)80119-1 / Curr. Opin. Cell Biol. / SCF and APC: the yin and yang of cell cycle regulated proteolysis by Peters (1998)
  40. 10.1126/science.276.5313.806 / Science / Cell cycle-dependent establishment of a late replication program by Raghuraman (1997)
  41. 10.1016/0076-6879(83)01015-0 / Methods Enzymol. / One-step gene disruption in yeast by Rothstein (1983)
  42. 10.1101/gad.7.7a.1160 / Genes Dev. / CLB5 and CLB6, a new pair of B cyclins involved in DNA replication in Saccharomyces cerevisiae by Schwob (1993)
  43. {'key': '2022010513521624600_R43', 'first-page': '233', 'article-title': 'The B-type cyclin kinase inhibitor p40SIC1 controls the G1 to S phase transition in Saccharomyces cerevisiae', 'volume': '79', 'author': 'Schwob', 'year': '1994', 'journal-title': 'Mol. Cell. Biol.'} / Mol. Cell. Biol. / The B-type cyclin kinase inhibitor p40SIC1 controls the G1 to S phase transition in Saccharomyces cerevisiae by Schwob (1994)
  44. 10.1242/jcs.113.12.2111 / J. Cell Sci. / Cdc7p-Dbf4p becomes famous in the cell cycle by Sclafani (2000)
  45. {'key': '2022010513521624600_R45', 'first-page': '1618', 'article-title': 'Conservative replication of double-stranded RNA in Saccharomyces cerevisiae by displacement of progeny single strands', 'volume': '4', 'author': 'Sclafani', 'year': '1984', 'journal-title': 'Mol. Cell. Biol.'} / Mol. Cell. Biol. / Conservative replication of double-stranded RNA in Saccharomyces cerevisiae by displacement of progeny single strands by Sclafani (1984)
  46. {'key': '2022010513521624600_R46', 'first-page': '293', 'article-title': 'Differential regulation of the yeast CDC7 gene during mitosis and meiosis', 'volume': '8', 'author': 'Sclafani', 'year': '1988', 'journal-title': 'Mol. Cell. Biol.'} / Mol. Cell. Biol. / Differential regulation of the yeast CDC7 gene during mitosis and meiosis by Sclafani (1988)
  47. 10.1002/(SICI)1097-0061(19990315)15:4<295::AID-YEA377>3.0.CO;2-Z / Yeast / Identification and characterization of individual cyclin-dependent kinase complexes from Saccharomyces cerevisiae by Shellman (1999)
  48. {'key': '2022010513521624600_R48', 'volume-title': 'Methods in Yeast Genetics', 'author': 'Sherman', 'year': '1979'} / Methods in Yeast Genetics by Sherman (1979)
  49. 10.1093/genetics/122.1.19 / Genetics / A system of shuttle vectors and yeast host strains designed for efficient manipulation of DNA in Saccharomyces cerevisiae by Sikorski (1989)
  50. 10.1091/mbc.9.12.3273 / Mol. Biol. Cell / Comprehensive identification of cell cycle-regulated genes of the yeast Saccharomyces cerevisiae by microarray hybridization by Spellman (1998)
  51. 10.1016/0092-8674(91)90416-V / Cell / The role of CDC28 and cyclins during mitosis in the budding yeast S. cerevisiae by Surana (1991)
  52. 10.1091/mbc.8.8.1427 / Mol. Biol. Cell / SIC1 is ubiquitinated in vitro by a pathway that requires CDC4, CDC34, and cyclin/CDK activities by Verma (1997)
  53. 10.1016/S1097-2765(00)80241-5 / Mol. Cell / Initiation of eukaryotic DNA replication: origin unwinding and sequential chromatin association of Cdc45, RPA, and DNA polymerase alpha by Walter (2000)
  54. 10.1074/jbc.M008107200 / J. Biol. Chem. / Evidence for sequential action of cdc7 and cdk2 protein kinases during initiation of DNA replication in Xenopus egg extracts by Walter (2000)
  55. 10.1093/emboj/18.19.5334 / EMBO J. / Cdc7p-Dbf4p kinase binds to chromatin during S phase and is regulated by both the APC and the RAD53 checkpoint pathway by Weinreich (1999)
  56. 10.1126/science.280.5363.593 / Science / Formation of a preinitiation complex by S-phase cyclin CDK-dependent loading of Cdc45p onto chromatin by Zou (1998)
  57. 10.1128/MCB.20.9.3086-3096.2000 / Mol. Cell. Biol. / Assembly of a complex containing cdc45p, replication protein A, and mcm2p at replication origins controlled by S-phase cyclin-dependent kinases and Cdc7p-Dbf4p kinase by Zou (2000)
Dates
Type When
Created 4 years, 4 months ago (April 23, 2021, 12:45 a.m.)
Deposited 3 years, 7 months ago (Jan. 5, 2022, 8:53 a.m.)
Indexed 1 year, 3 months ago (May 11, 2024, 3:49 a.m.)
Issued 23 years, 3 months ago (May 1, 2002)
Published 23 years, 3 months ago (May 1, 2002)
Published Online 23 years, 3 months ago (May 1, 2002)
Published Print 23 years, 3 months ago (May 1, 2002)
Funders 0

None

@article{Sclafani_2002, title={The mcm5-bob1 Bypass of Cdc7p/Dbf4p in DNA Replication Depends on Both Cdk1-Independent and Cdk1-Dependent Steps in Saccharomyces cerevisiae}, volume={161}, ISSN={1943-2631}, url={http://dx.doi.org/10.1093/genetics/161.1.47}, DOI={10.1093/genetics/161.1.47}, number={1}, journal={Genetics}, publisher={Oxford University Press (OUP)}, author={Sclafani, Robert A and Tecklenburg, Marianne and Pierce, Angela}, year={2002}, month=may, pages={47–57} }