KEGG   PATHWAY: sce04111Help
Entry
sce04111                    Pathway                                

Name
Cell cycle - yeast - Saccharomyces cerevisiae (budding 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
sce04111

All organismsOrtholog table
Module
Origin recognition complex [PATH:sce04111]
MCM complex [PATH:sce04111]
SCF-MET30 complex [PATH:sce04111]
APC/C complex [PATH:sce04111]
SCF-CDC4 complex [PATH:sce04111]
SCF-GRR1 complex [PATH:sce04111]
Other DBs
BSID: 
GO: 
Organism
Saccharomyces cerevisiae (budding yeast) [GN:sce]
Gene
CLN3; Cln3p [KO:K06646]
CDC28; cyclin-dependent serine/threonine-protein kinase CDC28 [KO:K04563] [EC:2.7.11.22]
SWI4; Swi4p [KO:K06649]
SWI6; Swi6p [KO:K06648]
CLN1; Cln1p [KO:K12760]
CLN2; Cln2p [KO:K06650]
SIC1; Sic1p [KO:K03085]
MBP1; Mbp1p [KO:K06647]
CLB6; Clb6p [KO:K06651]
CLB5; Clb5p [KO:K06651]
CDC6; AAA family ATPase CDC6 [KO:K02213]
ORC1; origin recognition complex subunit 1 [KO:K02603]
ORC2; origin recognition complex subunit 2 [KO:K02604]
ORC3; origin recognition complex subunit 3 [KO:K02605]
ORC4; origin recognition complex subunit 4 [KO:K02606]
ORC5; origin recognition complex subunit 5 [KO:K02607]
ORC6; origin recognition complex subunit 6 [KO:K02608]
MCM2; MCM DNA helicase complex subunit MCM2 [KO:K02540] [EC:3.6.4.12]
MCM3; MCM DNA helicase complex subunit MCM3 [KO:K02541] [EC:3.6.4.12]
MCM4; MCM DNA helicase complex subunit MCM4 [KO:K02212] [EC:3.6.4.12]
MCM5; MCM DNA helicase complex subunit MCM5 [KO:K02209] [EC:3.6.4.12]
MCM6; MCM DNA helicase complex subunit MCM6 [KO:K02542] [EC:3.6.4.12]
MCM7; mini-chromosome maintenance complex protein 7 [KO:K02210] [EC:3.6.4.12]
TAH11; Tah11p [KO:K12414]
CDC7; Cdc7p [KO:K02214] [EC:2.7.11.1]
DBF4; Dbf4p [KO:K02309]
CDC45; Cdc45p [KO:K06628]
MCM1; Mcm1p [KO:K12412]
WHI5; Whi5p [KO:K12413]
FAR1; Far1p [KO:K06652]
APC1; anaphase promoting complex subunit 1 [KO:K03348]
APC2; anaphase promoting complex subunit 2 [KO:K03349]
CDC27; anaphase promoting complex subunit CDC27 [KO:K03350]
APC4; anaphase promoting complex subunit 4 [KO:K03351]
APC5; anaphase promoting complex subunit 5 [KO:K03352]
CDC16; anaphase promoting complex subunit CDC16 [KO:K03353]
CDC23; anaphase promoting complex subunit CDC23 [KO:K03355]
APC9; anaphase promoting complex subunit 9 [KO:K03356]
DOC1; anaphase promoting complex subunit DOC1 [KO:K03357]
APC11; anaphase promoting complex subunit 11 [KO:K03358]
CDC26; anaphase promoting complex subunit CDC26 [KO:K03359]
SWM1; Swm1p [KO:K12416]
CDC20; Cdc20p [KO:K03363]
SKP1; SCF ubiquitin ligase subunit SKP1 [KO:K03094]
CDC53; cullin CDC53 [KO:K03347]
HRT1; SCF ubiquitin ligase complex subunit HRT1 [KO:K03868]
GRR1; SCF ubiquitin ligase complex subunit GRR1 [KO:K03360]
CDC4; SCF ubiquitin ligase complex subunit CDC4 [KO:K03361]
PCL1; Pcl1p [KO:K06656]
PCL2; Pcl2p [KO:K06657]
PHO85; cyclin-dependent serine/threonine-protein kinase PHO85 [KO:K06655] [EC:2.7.11.22]
PHO81; Pho81p [KO:K06653]
PHO80; Pho80p [KO:K06654]
PHO4; Pho4p [KO:K06658]
PHO2; Pho2p [KO:K02646]
CLB3; Clb3p [KO:K06659]
CLB4; Clb4p [KO:K06659]
MPS1; Mps1p [KO:K08866] [EC:2.7.12.1]
MAD1; Mad1p [KO:K06679]
MAD2; spindle checkpoint protein MAD2 [KO:K02537]
MAD3; Mad3p [KO:K06680]
BUB1; Bub1p [KO:K02178] [EC:2.7.11.1]
BUB3; Bub3p [KO:K02180]
DAM1; Dam1p [KO:K02307]
CHK1; Chk1p [KO:K02216] [EC:2.7.11.1]
PDS1; Pds1p [KO:K02627]
ESP1; Esp1p [KO:K02365] [EC:3.4.22.49]
SLK19; Slk19p [KO:K12575]
CDC55; protein phosphatase 2A regulatory subunit CDC55 [KO:K04354]
PPH21; phosphoprotein phosphatase 2A catalytic subunit PPH21 [KO:K04382] [EC:3.1.3.16]
PPH22; phosphoprotein phosphatase 2A catalytic subunit PPH22 [KO:K04382] [EC:3.1.3.16]
TPD3; protein phosphatase 2A structural subunit TPD3 [KO:K03456]
SPO12; Spo12p [KO:K12576]
FOB1; Fob1p [KO:K12577]
NET1; Net1p [KO:K06687]
CDC5; polo kinase CDC5 [KO:K06660] [EC:2.7.11.21]
BFA1; Bfa1p [KO:K02181]
BUB2; Bub2p [KO:K02179]
LTE1; Lte1p [KO:K06681]
TEM1; Ras family GTPase TEM1 [KO:K06682]
CDC15; Cdc15p [KO:K06683] [EC:2.7.11.1]
DBF2; serine/threonine-protein kinase DBF2 [KO:K06684] [EC:2.7.11.-]
DBF20; serine/threonine-protein kinase DBF20 [KO:K06686] [EC:2.7.11.-]
MOB1; Mob1p [KO:K06685]
CDC14; phosphoprotein phosphatase CDC14 [KO:K06639] [EC:3.1.3.48 3.1.3.16]
SWI5; Swi5p [KO:K09202]
CDH1; Cdh1p [KO:K03364]
CLB2; Clb2p [KO:K02220]
CLB1; Clb1p [KO:K02220]
MIH1; Mih1p [KO:K02555] [EC:3.1.3.48]
CAK1; Cak1p [KO:K06667] [EC:2.7.11.22]
CKS1; Cks1p [KO:K02219]
SWE1; Swe1p [KO:K03114] [EC:2.7.11.1]
MET30; Met30p [KO:K10259]
KCC4; Kcc4p [KO:K18639] [EC:2.7.11.1]
HSL1; Hsl1p [KO:K02515] [EC:2.7.11.-]
HSL7; Hsl7p [KO:K02516] [EC:2.1.1.125]
GIN4; Gin4p [KO:K06668] [EC:2.7.11.-]
MEC3; Mec3p [KO:K02544]
DDC1; Ddc1p [KO:K06663]
RAD17; Rad17p [KO:K02830] [EC:3.1.11.2]
RAD24; Rad24p [KO:K06662]
MEC1; Mec1p [KO:K02543]
LCD1; Lcd1p [KO:K12578]
RAD9; Rad9p [KO:K06661]
MRC1; Mrc1p [KO:K11272]
RAD53; Rad53p [KO:K02831] [EC:2.7.11.-]
DUN1; Dun1p [KO:K06641] [EC:2.7.11.1]
RFX1; Rfx1p [KO:K09175]
CYC8; Cyc8p [KO:K06665]
TUP1; Tup1p [KO:K06666]
SMC1; cohesin subunit SMC1 [KO:K06636]
SMC3; cohesin subunit SMC3 [KO:K06669]
MCD1; Mcd1p [KO:K06670]
IRR1; Irr1p [KO:K06671]
SCC2; Scc2p [KO:K06672]
SCC4; Scc4p [KO:K06673]
SMC2; condensin subunit SMC2 [KO:K06674]
SMC4; condensin subunit SMC4 [KO:K06675]
BRN1; Brn1p [KO:K06676]
YCS4; Ycs4p [KO:K06677]
YCG1; Ycg1p [KO:K06678]
FUS3; mitogen-activated serine/threonine-protein kinase FUS3 [KO:K04371] [EC:2.7.11.24]
PHO5; Pho5p [KO:K01078] [EC:3.1.3.2]
YHP1; Yhp1p [KO:K12411]
YOX1; Yox1p [KO:K12411]
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)
KO pathway
 

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