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
Cell cycle - yeast
ko04111

All organismsOrtholog 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]
Other DBs
BSID: 
GO: 
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
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
K02515  
serine/threonine-protein kinase HSL1,negative regulator of Swe1 kinase [EC:2.7.11.-]
K02516  
protein arginine N-methyltransferase 5 [EC:2.1.1.125]
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  
glucose repression mediator protein
K06666  
glucose repression regulatory protein 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)
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)
Reference
  Authors
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)
Reference
  Authors
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)
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)
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)
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)
Reference
PMID:7588610
  Authors
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)
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)
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)
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)
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)
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)
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)
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)
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)
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)
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)
Reference
PMID:9024629
  Authors
Deshaies RJ
  Title
Phosphorylation and proteolysis: partners in the regulation of cell division in budding yeast.
  Journal
Curr Opin Genet Dev 7:7-16 (1997)
Reference
  Authors
Asano S, Park JE, Sakchaisri K, Yu LR, Song S, Supavilai P, Veenstra TD, Lee KS
  Title
Concerted mechanism of Swe1/Wee1 regulation by multiple kinases in budding yeast.
  Journal
EMBO J 24:2194-204 (2005)
Reference
PMID:9716410
  Authors
Kaiser P, Sia RA, Bardes EG, Lew DJ, Reed SI
  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)
Reference
PMID:9925642
  Authors
Barral Y, Parra M, Bidlingmaier S, Snyder M
  Title
Nim1-related kinases coordinate cell cycle progression with the organization of the peripheral cytoskeleton in yeast.
  Journal
Genes Dev 13:176-87 (1999)
Reference
  Authors
Taylor SS
  Title
Chromosome segregation: dual control ensures fidelity.
  Journal
Curr Biol 9:R562-4 (1999)
Reference
  Authors
Lew DJ, Burke DJ
  Title
The spindle assembly and spindle position checkpoints.
  Journal
Annu Rev Genet 37:251-82 (2003)
Reference
  Authors
Simanis V
  Title
Events at the end of mitosis in the budding and fission yeasts.
  Journal
J Cell Sci 116:4263-75 (2003)
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
Amon A
  Title
Together until separin do us part.
  Journal
Nat Cell Biol 3:E12-4 (2001)
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)
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)
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)
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)
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)
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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