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
sce04111  Cell cycle - yeast
sce04111

Ortholog table
Module
sce_M00284  Origin recognition complex [PATH:sce04111]
sce_M00285  MCM complex [PATH:sce04111]
sce_M00379  SCF-MET30 complex [PATH:sce04111]
sce_M00389  APC/C complex [PATH:sce04111]
sce_M00407  SCF-CDC4 complex [PATH:sce04111]
sce_M00411  SCF-GRR1 complex [PATH:sce04111]
sce_M00692  Cell cycle - G1/S transition [PATH:sce04111]
sce_M00693  Cell cycle - G2/M transition [PATH:sce04111]
Other DBs
BSID: 958
GO: 0000278
Organism
Saccharomyces cerevisiae (budding yeast) [GN:sce]
Gene
YAL040C  CLN3; cyclin CLN3 [KO:K06646]
YBR160W  CDC28; cyclin-dependent serine/threonine-protein kinase CDC28 [KO:K04563] [EC:2.7.11.22]
YER111C  SWI4; SBF complex DNA-binding subunit SWI4 [KO:K06649]
YLR182W  SWI6; transcriptional regulator SWI6 [KO:K06648]
YMR199W  CLN1; cyclin CLN1 [KO:K12760]
YPL256C  CLN2; cyclin CLN2 [KO:K06650]
YLR079W  SIC1; cyclin-dependent protein serine/threonine kinase inhibiting protein SIC1 [KO:K03085]
YDL056W  MBP1; transcription factor MBP1 [KO:K06647]
YGR109C  CLB6; B-type cyclin CLB6 [KO:K06651]
YPR120C  CLB5; B-type cyclin CLB5 [KO:K06651]
YJL194W  CDC6; AAA family ATPase CDC6 [KO:K02213]
YML065W  ORC1; origin recognition complex subunit 1 [KO:K02603]
YBR060C  ORC2; origin recognition complex subunit 2 [KO:K02604]
YLL004W  ORC3; origin recognition complex subunit 3 [KO:K02605]
YPR162C  ORC4; origin recognition complex subunit 4 [KO:K02606]
YNL261W  ORC5; origin recognition complex subunit 5 [KO:K02607]
YHR118C  ORC6; origin recognition complex subunit 6 [KO:K02608]
YBL023C  MCM2; MCM DNA helicase complex subunit MCM2 [KO:K02540] [EC:3.6.4.12]
YEL032W  MCM3; MCM DNA helicase complex subunit MCM3 [KO:K02541] [EC:3.6.4.12]
YPR019W  MCM4; MCM DNA helicase complex subunit MCM4 [KO:K02212] [EC:3.6.4.12]
YLR274W  MCM5; MCM DNA helicase complex subunit MCM5 [KO:K02209] [EC:3.6.4.12]
YGL201C  MCM6; MCM DNA helicase complex subunit MCM6 [KO:K02542] [EC:3.6.4.12]
YBR202W  MCM7; mini-chromosome maintenance complex protein 7 [KO:K02210] [EC:3.6.4.12]
YJR046W  TAH11; Tah11p [KO:K12414]
YDL017W  CDC7; serine/threonine protein kinase CDC7 [KO:K02214] [EC:2.7.11.1]
YDR052C  DBF4; protein serine/threonine kinase activating protein DBF4 [KO:K02309]
YLR103C  CDC45; DNA replication initiation factor CDC45 [KO:K06628]
YMR043W  MCM1; transcription factor MCM1 [KO:K12412]
YOR083W  WHI5; transcriptional repressor WHI5 [KO:K12413]
YJL157C  FAR1; cyclin-dependent protein serine/threonine kinase inhibiting protein FAR1 [KO:K06652]
YNL172W  APC1; anaphase promoting complex subunit 1 [KO:K03348]
YLR127C  APC2; anaphase promoting complex subunit 2 [KO:K03349]
YBL084C  CDC27; anaphase promoting complex subunit CDC27 [KO:K03350]
YDR118W  APC4; anaphase promoting complex subunit 4 [KO:K03351]
YOR249C  APC5; anaphase promoting complex subunit 5 [KO:K03352]
YKL022C  CDC16; anaphase promoting complex subunit CDC16 [KO:K03353]
YHR166C  CDC23; anaphase promoting complex subunit CDC23 [KO:K03355]
YLR102C  APC9; anaphase promoting complex subunit 9 [KO:K03356]
YGL240W  DOC1; anaphase promoting complex subunit DOC1 [KO:K03357]
YDL008W  APC11; anaphase promoting complex subunit 11 [KO:K03358]
YFR036W  CDC26; anaphase promoting complex subunit CDC26 [KO:K03359]
YDR260C  SWM1; Swm1p [KO:K12416]
YGL116W  CDC20; ubiquitin-protein transferase activating protein CDC20 [KO:K03363]
YDR328C  SKP1; SCF ubiquitin ligase subunit SKP1 [KO:K03094]
YDL132W  CDC53; cullin CDC53 [KO:K03347]
YOL133W  HRT1; SCF ubiquitin ligase complex subunit HRT1 [KO:K03868] [EC:2.3.2.32]
YJR090C  GRR1; SCF ubiquitin ligase complex subunit GRR1 [KO:K03360]
YFL009W  CDC4; SCF ubiquitin ligase complex subunit CDC4 [KO:K03361]
YNL289W  PCL1; Pcl1p [KO:K06656]
YDL127W  PCL2; cyclin PCL2 [KO:K06657]
YPL031C  PHO85; cyclin-dependent serine/threonine-protein kinase PHO85 [KO:K06655] [EC:2.7.11.22]
YGR233C  PHO81; Pho81p [KO:K06653]
YOL001W  PHO80; Pho80p [KO:K06654]
YFR034C  PHO4; phosphate-sensing transcription factor PHO4 [KO:K06658]
YDL106C  PHO2; Pho2p [KO:K02646]
YDL155W  CLB3; B-type cyclin CLB3 [KO:K06659]
YLR210W  CLB4; B-type cyclin CLB4 [KO:K06659]
YDL028C  MPS1; serine/threonine/tyrosine protein kinase MPS1 [KO:K08866] [EC:2.7.12.1]
YGL086W  MAD1; coiled-coil domain-containing protein MAD1 [KO:K06679]
YJL030W  MAD2; spindle checkpoint protein MAD2 [KO:K02537]
YJL013C  MAD3; Mad3p [KO:K06680]
YGR188C  BUB1; protein kinase BUB1 [KO:K02178] [EC:2.7.11.1]
YOR026W  BUB3; Bub3p [KO:K02180]
YGR113W  DAM1; Dam1p [KO:K02307]
YBR274W  CHK1; serine/threonine protein kinase CHK1 [KO:K02216] [EC:2.7.11.1]
YDR113C  PDS1; securin [KO:K02627]
YGR098C  ESP1; separase [KO:K02365] [EC:3.4.22.49]
YOR195W  SLK19; Slk19p [KO:K12575]
YGL190C  CDC55; protein phosphatase 2A regulatory subunit CDC55 [KO:K04354]
YDL134C  PPH21; phosphoprotein phosphatase 2A catalytic subunit PPH21 [KO:K04382] [EC:3.1.3.16]
YDL188C  PPH22; phosphoprotein phosphatase 2A catalytic subunit PPH22 [KO:K04382] [EC:3.1.3.16]
YAL016W  TPD3; protein phosphatase 2A structural subunit TPD3 [KO:K03456]
YHR152W  SPO12; Spo12p [KO:K12576]
YDR110W  FOB1; replication fork barrier binding protein FOB1 [KO:K12577]
YJL076W  NET1; Net1p [KO:K06687]
YMR001C  CDC5; polo kinase CDC5 [KO:K06660] [EC:2.7.11.21]
YJR053W  BFA1; Bfa1p [KO:K02181]
YMR055C  BUB2; Bub2p [KO:K02179]
YAL024C  LTE1; mitotic regulator LTE1 [KO:K06681]
YML064C  TEM1; Ras family GTPase TEM1 [KO:K06682]
YAR019C  CDC15; serine/threonine protein kinase CDC15 [KO:K06683] [EC:2.7.11.1]
YGR092W  DBF2; serine/threonine-protein kinase DBF2 [KO:K06684] [EC:2.7.11.-]
YPR111W  DBF20; serine/threonine-protein kinase DBF20 [KO:K06686] [EC:2.7.11.-]
YIL106W  MOB1; Mob1p [KO:K06685]
YFR028C  CDC14; phosphoprotein phosphatase CDC14 [KO:K06639] [EC:3.1.3.48 3.1.3.16]
YDR146C  SWI5; DNA-binding transcription factor SWI5 [KO:K09202]
YGL003C  CDH1; Cdh1p [KO:K03364]
YPR119W  CLB2; B-type cyclin CLB2 [KO:K02220]
YGR108W  CLB1; B-type cyclin CLB1 [KO:K02220]
YMR036C  MIH1; putative tyrosine protein phosphatase MIH1 [KO:K02555] [EC:3.1.3.48]
YFL029C  CAK1; cyclin-dependent protein kinase-activating kinase CAK1 [KO:K06667] [EC:2.7.11.22]
YBR135W  CKS1; cyclin-dependent protein kinase regulatory subunit CKS1 [KO:K02219]
YJL187C  SWE1; tyrosine protein kinase SWE1 [KO:K03114] [EC:2.7.11.1]
YIL046W  MET30; ubiquitin-binding SDF ubiquitin ligase complex subunit MET30 [KO:K10259]
YCL024W  KCC4; serine/threonine protein kinase [KO:K18639] [EC:2.7.11.1]
YKL101W  HSL1; protein kinase HSL1 [KO:K02515] [EC:2.7.11.-]
YBR133C  HSL7; protein arginine N-methyltransferase [KO:K02516] [EC:2.1.1.320]
YDR507C  GIN4; protein kinase GIN4 [KO:K06668] [EC:2.7.11.-]
YLR288C  MEC3; Mec3p [KO:K02544]
YPL194W  DDC1; Ddc1p [KO:K06663]
YOR368W  RAD17; Rad17p [KO:K02830] [EC:3.1.11.2]
YER173W  RAD24; Rad24p [KO:K06662]
YBR136W  MEC1; protein kinase MEC1 [KO:K02543]
YDR499W  LCD1; Lcd1p [KO:K12578]
YDR217C  RAD9; chromatin-binding protein RAD9 [KO:K06661]
YCL061C  MRC1; chromatin-modulating protein MRC1 [KO:K11272]
YPL153C  RAD53; serine/threonine/tyrosine protein kinase RAD53 [KO:K02831] [EC:2.7.11.-]
YDL101C  DUN1; serine/threonine protein kinase DUN1 [KO:K06641] [EC:2.7.11.1]
YLR176C  RFX1; Rfx1p [KO:K09175]
YBR112C  CYC8; transcription regulator CYC8 [KO:K06665]
YCR084C  TUP1; chromatin-silencing transcriptional regulator TUP1 [KO:K06666]
YFL008W  SMC1; cohesin subunit SMC1 [KO:K06636]
YJL074C  SMC3; cohesin subunit SMC3 [KO:K06669]
YDL003W  MCD1; kleisin alpha [KO:K06670]
YIL026C  IRR1; Irr1p [KO:K06671]
YDR180W  SCC2; cohesin-loading factor complex subunit SCC2 [KO:K06672]
YER147C  SCC4; cohesin-loading factor complex subunit SCC4 [KO:K06673]
YFR031C  SMC2; condensin subunit SMC2 [KO:K06674]
YLR086W  SMC4; condensin subunit SMC4 [KO:K06675]
YBL097W  BRN1; condensin subunit BRN1 [KO:K06676]
YLR272C  YCS4; condensin subunit YCS4 [KO:K06677]
YDR325W  YCG1; condensin subunit YCG1 [KO:K06678]
YBL016W  FUS3; mitogen-activated serine/threonine-protein kinase FUS3 [KO:K04371] [EC:2.7.11.24]
YBR093C  PHO5; acid phosphatase PHO5 [KO:K01078] [EC:3.1.3.2]
YDR451C  YHP1; Yhp1p [KO:K12411]
YML027W  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)
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
  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)
DOI:10.1016/j.cell.2004.05.024
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)
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
  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)
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
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)
DOI:10.1016/S0959-437X(97)80103-7
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)
DOI:10.1038/sj.emboj.7600683
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)
DOI:10.1101/gad.12.16.2587
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)
DOI:10.1101/gad.13.2.176
Reference
  Authors
Taylor SS
  Title
Chromosome segregation: dual control ensures fidelity.
  Journal
Curr Biol 9:R562-4 (1999)
DOI:10.1016/S0960-9822(99)80355-8
Reference
  Authors
Lew DJ, Burke DJ
  Title
The spindle assembly and spindle position checkpoints.
  Journal
Annu Rev Genet 37:251-82 (2003)
DOI:10.1146/annurev.genet.37.042203.120656
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)
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
Amon A
  Title
Together until separin do us part.
  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)
DOI:10.1111/j.1742-4658.2008.06693.x
KO pathway
ko04111   

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