KEGG   PATHWAY: ko04111Help
Entry
ko04111                     Pathway                                

Name
Cell cycle - yeast
Description
Mitotic cell cycle progression is accomplished through a reproducible sequence of events, DNA replication (S phase) and mitosis (M phase) separated temporally by gaps (G1 and G2 phases). G1, S, and G2 phases are collectively known as interphase. In yeast Cdc28 is the catalytic subunit of the cyclin-dependent kinase (CDK). At G1 phase Cdc28 associates with G1-cyclins Cln1 to Cln3, while B-type cyclins Clb1 to Clb6 regulate Cdc28 during S, G2, and M phases. Cln3/Cdc28 activity is required for cells to pass through 'start', the commitment point in G1. When Cln3/Cdc28 accumulates more than a certain threshold, SBF (Swi4/Swi6) and MBF (Mbp1/Swi6) are activated, promoting transcription of Cln1, Cln2, and other genes required for S-phase progression. Cln1 and Cln2 interacting with Cdc28 promote activation of B-type cyclin associated CDK, which drives DNA replication and entry into mitosis. Specifically, Cdc28 association with Clb2 and Clb1 promotes entry into mitosis. Cells suffering from DNA damage, spindle misorientation, or spindle assembly defect do not undergo the metaphase-anaphase transition for chromosome segregation and fail to exit from mitosis. The spindle assembly checkpoint activates Mad2, which in turn prevents chromosome segregation by inhibiting degradation of the securin Pds1. Moreover, Pds1 is phosphorylated and stabilized in response to DNA damage in a Chk1-dependent manner. The spindle checkpoint is also involved in the Cdc14 release from the nucleolus. Cdc14 dephosphorylates Swi5, Sic1, and Cdh1, leading to inhibition of Cdc28 and degradation of cyclin required for mitotic exit.
Class
Cellular Processes; Cell growth and death
BRITE hierarchy
Pathway map
ko04111  Cell cycle - yeast
ko04111

Ortholog table
Module
M00284  Origin recognition complex [PATH:ko04111]
M00285  MCM complex [PATH:ko04111]
M00379  SCF-MET30 complex [PATH:ko04111]
M00389  APC/C complex [PATH:ko04111]
M00407  SCF-CDC4 complex [PATH:ko04111]
M00411  SCF-GRR1 complex [PATH:ko04111]
M00692  Cell cycle - G1/S transition [PATH:ko04111]
M00693  Cell cycle - G2/M transition [PATH:ko04111]
Other DBs
BSID: 464
GO: 0000278
Orthology
K06646  G1/S-specific cyclin CLN3
K04563  cyclin-dependent kinase [EC:2.7.11.22]
K06649  regulatory protein SWI4
K06648  regulatory protein SWI6
K12760  G1/S-specific cyclin CLN1
K06650  G1/S-specific cyclin CLN2
K03085  substrate and inhibitor of the cyclin-dependent protein kinase CDC28
K06647  transcription factor MBP1
K06651  S-phase entry cyclin 5/6
K02213  cell division control protein 6
K02603  origin recognition complex subunit 1
K02604  origin recognition complex subunit 2
K02605  origin recognition complex subunit 3
K02606  origin recognition complex subunit 4
K02607  origin recognition complex subunit 5
K02608  origin recognition complex subunit 6
K02540  DNA replication licensing factor MCM2 [EC:3.6.4.12]
K02541  DNA replication licensing factor MCM3 [EC:3.6.4.12]
K02212  DNA replication licensing factor MCM4 [EC:3.6.4.12]
K02209  DNA replication licensing factor MCM5 [EC:3.6.4.12]
K02542  DNA replication licensing factor MCM6 [EC:3.6.4.12]
K02210  DNA replication licensing factor MCM7 [EC:3.6.4.12]
K12414  DNA replication licensing factor, required for pre-replication complex assembly
K02214  cell division control protein 7 [EC:2.7.11.1]
K02309  regulatory subunit for Cdc7p protein kinase
K06628  cell division control protein 45
K12412  pheromone receptor transcription factor
K12413  G1-specific transcriptional repressor WHI5
K06652  cyclin-dependent kinase inhibitor FAR1
K03348  anaphase-promoting complex subunit 1
K03349  anaphase-promoting complex subunit 2
K03350  anaphase-promoting complex subunit 3
K03351  anaphase-promoting complex subunit 4
K03352  anaphase-promoting complex subunit 5
K03353  anaphase-promoting complex subunit 6
K03354  anaphase-promoting complex subunit 7
K03355  anaphase-promoting complex subunit 8
K03356  anaphase-promoting complex subunit 9
K03357  anaphase-promoting complex subunit 10
K03358  anaphase-promoting complex subunit 11
K03359  anaphase-promoting complex subunit 12
K12416  anaphase-promoting complex subunit SWM1
K03363  cell division cycle 20, cofactor of APC complex
K03094  S-phase kinase-associated protein 1
K03347  cullin 1
K03868  RING-box protein 1 [EC:2.3.2.32]
K03360  F-box and leucine-rich repeat protein GRR1
K03361  F-box and WD-40 domain protein CDC4
K06656  G1/S-specific cyclin PLC1
K06657  G1/S-specific cyclin PLC2
K06655  negative regulator of the PHO system [EC:2.7.11.22]
K06653  CDK inhibitor PHO81
K06654  phosphate system cyclin PHO80
K06658  phosphate system positive regulatory protein PHO4
K02646  regulatory protein PHO2
K06659  G2/mitotic-specific cyclin 3/4
K08866  serine/threonine-protein kinase TTK/MPS1 [EC:2.7.12.1]
K06679  mitotic spindle assembly checkpoint protein MAD1
K02537  mitotic spindle assembly checkpoint protein MAD2
K06680  spindle assembly checkpoint component MAD3
K02178  checkpoint serine/threonine-protein kinase [EC:2.7.11.1]
K02180  cell cycle arrest protein BUB3
K02307  DASH complex subunit DAM1
K02216  serine/threonine-protein kinase Chk1 [EC:2.7.11.1]
K02627  cell cycle regulator
K02365  separase [EC:3.4.22.49]
K12575  kinetochore protein SLK19
K04354  serine/threonine-protein phosphatase 2A regulatory subunit B
K04382  serine/threonine-protein phosphatase 2A catalytic subunit [EC:3.1.3.16]
K03456  serine/threonine-protein phosphatase 2A regulatory subunit A
K12576  sporulation-specific protein 12
K12577  DNA replication fork-blocking protein FOB1
K06687  nucleolar protein involved in exit from mitosis
K06660  cell cycle serine/threonine-protein kinase CDC5/MSD2 [EC:2.7.11.21]
K02181  cell cycle arrest protein BFA1
K02179  cell cycle arrest protein BUB2
K06681  Gdp/GTP exchange factor required for growth at low temperatures
K06682  Gtp-binding protein of the ras superfamily involved in termination of M-phase
K06683  cell division control protein CDC15 [EC:2.7.11.1]
K06684  cell cycle protein kinase DBF2 [EC:2.7.11.-]
K06686  cell cycle protein kinase DBF20 [EC:2.7.11.-]
K06685  MOB kinase activator 1
K06639  cell division cycle 14 [EC:3.1.3.48 3.1.3.16]
K09202  regulatory protein SWI5
K03364  cell division cycle 20-like protein 1, cofactor of APC complex
K02220  G2/mitotic-specific cyclin 1/2
K02555  M-phase inducer tyrosine phosphatase [EC:3.1.3.48]
K06667  serine/threonine-protein kinase CAK1 [EC:2.7.11.22]
K02219  cyclin-dependent kinase regulatory subunit CKS1
K03114  mitosis inhibitor protein kinase SWE1 [EC:2.7.11.1]
K10259  F-box and WD-40 domain protein MET30
K18669  dual specificity tyrosine-phosphorylation-regulated kinase 2/3/4 [EC:2.7.12.1]
K18679  mitosis inducer protein kinase Cdr2 [EC:2.7.11.1]
K18680  mitosis inducer protein kinase Cdr1 [EC:2.7.11.1]
K18639  serine/threonine-protein kinase KCC4 [EC:2.7.11.1]
K02515  serine/threonine-protein kinase HSL1, negative regulator of Swe1 kinase [EC:2.7.11.-]
K02516  type II protein arginine methyltransferase [EC:2.1.1.320]
K06668  serine/threonine-protein kinase GIN4 [EC:2.7.11.-]
K02544  G2-specific checkpoint protein
K06663  DNA damage checkpoint protein
K02830  cell cycle checkpoint protein [EC:3.1.11.2]
K06662  cell cycle checkpoint protein
K02543  cell cycle checkpoint protein MEC1
K12578  DNA damage checkpoint protein LCD1
K06661  DNA repair protein RAD9
K11272  mediator of replication checkpoint protein 1
K02831  ser/thr/tyr protein kinase RAD53 [EC:2.7.11.-]
K06641  serine/threonine-protein kinase Chk2 [EC:2.7.11.1]
K09175  regulatory factor X, other
K06665  general transcriptional corepressor CYC8
K06666  general transcriptional corepressor TUP1
K06636  structural maintenance of chromosome 1
K06669  structural maintenance of chromosome 3 (chondroitin sulfate proteoglycan 6)
K06670  cohesin complex subunit SCC1
K06671  cohesin complex subunit SA-1/2
K06672  cohesin loading factor subunit SCC2
K06673  cohesin loading factor subunit SCC4
K06674  structural maintenance of chromosome 2
K06675  structural maintenance of chromosome 4
K06676  condensin complex subunit 2
K06677  condensin complex subunit 1
K06678  condensin complex subunit 3
Compound
C00009  Orthophosphate
C00575  3',5'-Cyclic AMP
Reference
  Authors
Devault A, Vallen EA, Yuan T, Green S, Bensimon A, Schwob E
  Title
Identification of Tah11/Sid2 as the ortholog of the replication licensing factor Cdt1 in Saccharomyces cerevisiae.
  Journal
Curr Biol 12:689-94 (2002)
DOI:10.1016/S0960-9822(02)00768-6
Reference
  Authors
de Bruin RA, McDonald WH, Kalashnikova TI, Yates J 3rd, Wittenberg C
  Title
Cln3 activates G1-specific transcription via phosphorylation of the SBF bound repressor Whi5.
  Journal
Cell 117:887-98 (2004)
DOI:10.1016/j.cell.2004.05.025
Reference
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Costanzo M, Nishikawa JL, Tang X, Millman JS, Schub O, Breitkreuz K, Dewar D, Rupes I, Andrews B, Tyers M
  Title
CDK activity antagonizes Whi5, an inhibitor of G1/S transcription in yeast.
  Journal
Cell 117:899-913 (2004)
DOI:10.1016/j.cell.2004.05.024
Reference
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Pramila T, Miles S, GuhaThakurta D, Jemiolo D, Breeden LL
  Title
Conserved homeodomain proteins interact with MADS box protein Mcm1 to restrict ECB-dependent transcription to the M/G1 phase of the cell cycle.
  Journal
Genes Dev 16:3034-45 (2002)
DOI:10.1101/gad.1034302
Reference
  Authors
Schwickart M, Havlis J, Habermann B, Bogdanova A, Camasses A, Oelschlaegel T, Shevchenko A, Zachariae W
  Title
Swm1/Apc13 is an evolutionarily conserved subunit of the anaphase-promoting complex stabilizing the association of Cdc16 and Cdc27.
  Journal
Mol Cell Biol 24:3562-76 (2004)
DOI:10.1128/MCB.24.8.3562-3576.2004
Reference
  Authors
Penkner AM, Prinz S, Ferscha S, Klein F
  Title
Mnd2, an essential antagonist of the anaphase-promoting complex during meiotic prophase.
  Journal
Cell 120:789-801 (2005)
DOI:10.1016/j.cell.2005.01.017
Reference
  Authors
Pesin JA, Orr-Weaver TL
  Title
Regulation of APC/C activators in mitosis and meiosis.
  Journal
Annu Rev Cell Dev Biol 24:475-99 (2008)
DOI:10.1146/annurev.cellbio.041408.115949
Reference
PMID:7588610
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Dirick L, Bohm T, Nasmyth K
  Title
Roles and regulation of Cln-Cdc28 kinases at the start of the cell cycle of Saccharomyces cerevisiae.
  Journal
EMBO J 14:4803-13 (1995)
Reference
  Authors
Bahler J
  Title
Cell-cycle control of gene expression in budding and fission yeast.
  Journal
Annu Rev Genet 39:69-94 (2005)
DOI:10.1146/annurev.genet.39.110304.095808
Reference
PMID:8066461
  Authors
Peter M, Herskowitz I
  Title
Direct inhibition of the yeast cyclin-dependent kinase Cdc28-Cln by Far1.
  Journal
Science 265:1228-31 (1994)
DOI:10.1126/science.8066461
Reference
PMID:9367986
  Authors
Henchoz S, Chi Y, Catarin B, Herskowitz I, Deshaies RJ, Peter M
  Title
Phosphorylation- and ubiquitin-dependent degradation of the cyclin-dependent kinase inhibitor Far1p in budding yeast.
  Journal
Genes Dev 11:3046-60 (1997)
DOI:10.1101/gad.11.22.3046
Reference
PMID:9346239
  Authors
Feldman RM, Correll CC, Kaplan KB, Deshaies RJ
  Title
A complex of Cdc4p, Skp1p, and Cdc53p/cullin catalyzes ubiquitination of the phosphorylated CDK inhibitor Sic1p.
  Journal
Cell 91:221-30 (1997)
DOI:10.1016/S0092-8674(00)80404-3
Reference
PMID:7954792
  Authors
Schwob E, Bohm T, Mendenhall MD, Nasmyth K
  Title
The B-type cyclin kinase inhibitor p40SIC1 controls the G1 to S transition in S. cerevisiae.
  Journal
Cell 79:233-44 (1994)
DOI:10.1016/0092-8674(94)90193-7
Reference
PMID:9841670
  Authors
Mendenhall MD, Hodge AE
  Title
Regulation of Cdc28 cyclin-dependent protein kinase activity during the cell cycle of the yeast Saccharomyces cerevisiae.
  Journal
Microbiol Mol Biol Rev 62:1191-243 (1998)
Reference
  Authors
Zachariae W, Nasmyth K
  Title
Whose end is destruction: cell division and the anaphase-promoting complex.
  Journal
Genes Dev 13:2039-58 (1999)
DOI:10.1101/gad.13.16.2039
Reference
  Authors
Jares P, Donaldson A, Blow JJ
  Title
The Cdc7/Dbf4 protein kinase: target of the S phase checkpoint?
  Journal
EMBO Rep 1:319-22 (2000)
DOI:10.1093/embo-reports/kvd076
Reference
  Authors
Elsasser S, Chi Y, Yang P, Campbell JL
  Title
Phosphorylation controls timing of Cdc6p destruction: A biochemical analysis.
  Journal
Mol Biol Cell 10:3263-77 (1999)
DOI:10.1091/mbc.10.10.3263
Reference
  Authors
Skowyra D, Koepp DM, Kamura T, Conrad MN, Conaway RC, Conaway JW, Elledge SJ, Harper JW
  Title
Reconstitution of G1 cyclin ubiquitination with complexes containing SCFGrr1 and Rbx1.
  Journal
Science 284:662-5 (1999)
DOI:10.1126/science.284.5414.662
Reference
  Authors
Mouillon JM, Persson BL
  Title
New aspects on phosphate sensing and signalling in Saccharomyces cerevisiae.
  Journal
FEMS Yeast Res 6:171-6 (2006)
DOI:10.1111/j.1567-1364.2006.00036.x
Reference
  Authors
Bean JM, Siggia ED, Cross FR
  Title
High functional overlap between MluI cell-cycle box binding factor and Swi4/6 cell-cycle box binding factor in the G1/S transcriptional program in Saccharomyces cerevisiae.
  Journal
Genetics 171:49-61 (2005)
DOI:10.1534/genetics.105.044560
Reference
PMID:9024629
  Authors
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  Title
Phosphorylation and proteolysis: partners in the regulation of cell division in budding yeast.
  Journal
Curr Opin Genet Dev 7:7-16 (1997)
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Reference
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  Journal
EMBO J 24:2194-204 (2005)
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Reference
PMID:9716410
  Authors
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  Title
Cdc34 and the F-box protein Met30 are required for degradation of the Cdk-inhibitory kinase Swe1.
  Journal
Genes Dev 12:2587-97 (1998)
DOI:10.1101/gad.12.16.2587
Reference
PMID:9925642
  Authors
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  Title
Nim1-related kinases coordinate cell cycle progression with the organization of the peripheral cytoskeleton in yeast.
  Journal
Genes Dev 13:176-87 (1999)
DOI:10.1101/gad.13.2.176
Reference
  Authors
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  Title
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  Journal
Curr Biol 9:R562-4 (1999)
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Reference
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  Title
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  Journal
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Reference
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  Title
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  Journal
J Cell Sci 116:4263-75 (2003)
DOI:10.1242/jcs.00807
Reference
PMID:8131744
  Authors
Toyn JH, Johnston LH
  Title
The Dbf2 and Dbf20 protein kinases of budding yeast are activated after the metaphase to anaphase cell cycle transition.
  Journal
EMBO J 13:1103-13 (1994)
Reference
  Authors
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  Title
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  Journal
Nat Cell Biol 3:E12-4 (2001)
DOI:10.1038/35050642
Reference
  Authors
Ciosk R, Shirayama M, Shevchenko A, Tanaka T, Toth A, Shevchenko A, Nasmyth K
  Title
Cohesin's binding to chromosomes depends on a separate complex consisting of Scc2 and Scc4 proteins.
  Journal
Mol Cell 5:243-54 (2000)
DOI:10.1016/S1097-2765(00)80420-7
Reference
  Authors
Freeman L, Aragon-Alcaide L, Strunnikov A
  Title
The condensin complex governs chromosome condensation and mitotic transmission of rDNA.
  Journal
J Cell Biol 149:811-24 (2000)
DOI:10.1083/jcb.149.4.811
Reference
  Authors
Fu Y, Pastushok L, Xiao W
  Title
DNA damage-induced gene expression in Saccharomyces cerevisiae.
  Journal
FEMS Microbiol Rev 32:908-26 (2008)
DOI:10.1111/j.1574-6976.2008.00126.x
Reference
  Authors
Friedel AM, Pike BL, Gasser SM
  Title
ATR/Mec1: coordinating fork stability and repair.
  Journal
Curr Opin Cell Biol 21:237-44 (2009)
DOI:10.1016/j.ceb.2009.01.017
Reference
  Authors
Chen SH, Zhou H
  Title
Reconstitution of Rad53 activation by Mec1 through adaptor protein Mrc1.
  Journal
J Biol Chem 284:18593-604 (2009)
DOI:10.1074/jbc.M109.018242
Reference
  Authors
Amon A
  Title
A decade of Cdc14--a personal perspective. Delivered on 9 July 2007 at the 32nd FEBS Congress in Vienna, Austria.
  Journal
FEBS J 275:5774-84 (2008)
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