KEGG   PATHWAY: ko04111
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
Pathway map
ko04111  Cell cycle - yeast
ko04111

Other DBs
GO: 0000278
Orthology
K02178  BUB1; checkpoint serine/threonine-protein kinase [EC:2.7.11.1]
K02179  BUB2; cell cycle arrest protein BUB2
K02180  BUB3; cell cycle arrest protein BUB3
K02181  BFA1; cell cycle arrest protein BFA1
K02209  MCM5, CDC46; DNA replication licensing factor MCM5 [EC:5.6.2.3]
K02210  MCM7, CDC47; DNA replication licensing factor MCM7 [EC:5.6.2.3]
K02212  MCM4, CDC54; DNA replication licensing factor MCM4 [EC:5.6.2.3]
K02213  CDC6; cell division control protein 6
K02214  CDC7; cell division control protein 7 [EC:2.7.11.1]
K02216  CHEK1; serine/threonine-protein kinase CHEK1 [EC:2.7.11.1]
K02219  CKS1; cyclin-dependent kinase regulatory subunit CKS1
K02220  CLB1; G2/mitotic-specific cyclin 1
K02307  DAM1; DASH complex subunit DAM1
K02309  DBF4; regulatory subunit for Cdc7p protein kinase
K02365  ESP1; separase [EC:3.4.22.49]
K02515  HSL1; serine/threonine-protein kinase HSL1, negative regulator of Swe1 kinase [EC:2.7.11.-]
K02516  PRMT5, HSL7; type II protein arginine methyltransferase [EC:2.1.1.320]
K02537  MAD2; mitotic spindle assembly checkpoint protein MAD2
K02540  MCM2; DNA replication licensing factor MCM2 [EC:5.6.2.3]
K02541  MCM3; DNA replication licensing factor MCM3 [EC:5.6.2.3]
K02542  MCM6; DNA replication licensing factor MCM6 [EC:5.6.2.3]
K02543  MEC1; cell cycle checkpoint protein MEC1
K02544  MEC3; G2-specific checkpoint protein
K02555  MIH1; M-phase inducer tyrosine phosphatase [EC:3.1.3.48]
K02603  ORC1; origin recognition complex subunit 1
K02604  ORC2; origin recognition complex subunit 2
K02605  ORC3; origin recognition complex subunit 3
K02606  ORC4; origin recognition complex subunit 4
K02607  ORC5; origin recognition complex subunit 5
K02608  ORC6; origin recognition complex subunit 6
K02627  PDS1; cell cycle regulator
K02646  PHO2; regulatory protein PHO2
K02830  HRAD1, RAD17; cell cycle checkpoint protein [EC:3.1.11.2]
K02831  RAD53; ser/thr/tyr protein kinase RAD53 [EC:2.7.11.-]
K03085  SIC1; substrate and inhibitor of the cyclin-dependent protein kinase CDC28
K03094  SKP1, CBF3D; S-phase kinase-associated protein 1
K03114  SWE1; mitosis inhibitor protein kinase SWE1 [EC:2.7.11.1]
K03347  CUL1, CDC53; cullin 1
K03348  APC1, ANAPC1; anaphase-promoting complex subunit 1
K03349  APC2, ANAPC2; anaphase-promoting complex subunit 2
K03350  APC3, CDC27; anaphase-promoting complex subunit 3
K03351  APC4, ANAPC4; anaphase-promoting complex subunit 4
K03352  APC5, ANAPC5; anaphase-promoting complex subunit 5
K03353  APC6, CDC16; anaphase-promoting complex subunit 6
K03354  APC7, ANAPC7; anaphase-promoting complex subunit 7
K03355  APC8, CDC23; anaphase-promoting complex subunit 8
K03356  APC9; anaphase-promoting complex subunit 9
K03357  APC10, ANAPC10, DOC1; anaphase-promoting complex subunit 10
K03358  APC11, ANAPC11; anaphase-promoting complex subunit 11
K03359  APC12, CDC26; anaphase-promoting complex subunit 12
K03360  GRR1; F-box and leucine-rich repeat protein GRR1
K03361  CDC4; F-box and WD-40 domain protein CDC4
K03363  CDC20; cell division cycle 20, cofactor of APC complex
K03364  CDH1, FZR1; cell division cycle 20-like protein 1, cofactor of APC complex
K03456  PPP2R1; serine/threonine-protein phosphatase 2A regulatory subunit A
K03868  RBX1, ROC1; E3 ubiquitin-protein ligase RBX1 [EC:2.3.2.32]
K04354  PPP2R2; serine/threonine-protein phosphatase 2A regulatory subunit B
K04371  ERK, MAPK1_3; mitogen-activated protein kinase 1/3 [EC:2.7.11.24]
K04382  PPP2C; serine/threonine-protein phosphatase 2A catalytic subunit [EC:3.1.3.16]
K04563  CDC28, CDC2; cyclin-dependent kinase [EC:2.7.11.22]
K06628  CDC45; cell division control protein 45
K06636  SMC1; structural maintenance of chromosome 1
K06639  CDC14; cell division cycle 14 [EC:3.1.3.16 3.1.3.48]
K06641  CHEK2; serine/threonine-protein kinase CHEK2 [EC:2.7.11.1]
K06646  CLN3; G1/S-specific cyclin CLN3
K06647  MBP1; transcription factor MBP1
K06648  SWI6; regulatory protein SWI6
K06649  SWI4; regulatory protein SWI4
K06650  CLN2; G1/S-specific cyclin CLN2
K06651  CLB5_6; S-phase entry cyclin 5/6
K06652  FAR1; cyclin-dependent kinase inhibitor FAR1
K06653  PHO81; CDK inhibitor PHO81
K06654  PHO80; phosphate system cyclin PHO80
K06655  PHO85; negative regulator of the PHO system [EC:2.7.11.22]
K06656  PCL1; PHO85 cyclin-1
K06657  PCL2_9; PHO85 cyclin-2/9
K06658  PHO4; phosphate system positive regulatory protein PHO4
K06659  CLB3_4; G2/mitotic-specific cyclin 3/4
K06660  CDC5; cell cycle serine/threonine-protein kinase CDC5/MSD2 [EC:2.7.11.21]
K06661  RAD9; DNA repair protein RAD9
K06662  HRAD17, RAD24; cell cycle checkpoint protein
K06663  DDC1; DNA damage checkpoint protein
K06665  SSN6, CYC8; general transcriptional corepressor CYC8
K06666  TUP1; general transcriptional corepressor TUP1
K06667  CAK1; serine/threonine-protein kinase CAK1 [EC:2.7.11.22]
K06668  GIN4; serine/threonine-protein kinase GIN4 [EC:2.7.11.-]
K06669  SMC3, CSPG6; structural maintenance of chromosome 3 (chondroitin sulfate proteoglycan 6)
K06670  SCC1, MCD1, RAD21; cohesin complex subunit SCC1
K06671  STAG1_2, SCC3, IRR1; cohesin complex subunit SA-1/2
K06672  SCC2, NIPBL; cohesin loading factor subunit SCC2
K06673  SCC4; cohesin loading factor subunit SCC4
K06674  SMC2; structural maintenance of chromosome 2
K06675  SMC4; structural maintenance of chromosome 4
K06676  BRRN1, BRN1, CAPH; condensin complex subunit 2
K06677  YCS4, CNAP1, CAPD2; condensin complex subunit 1
K06678  YCG1, CAPG; condensin complex subunit 3
K06679  MAD1; mitotic spindle assembly checkpoint protein MAD1
K06680  MAD3; spindle assembly checkpoint component MAD3
K06681  LTE1; Gdp/GTP exchange factor required for growth at low temperatures
K06682  TEM1; Gtp-binding protein of the ras superfamily involved in termination of M-phase
K06683  CDC15; cell division control protein CDC15 [EC:2.7.11.1]
K06684  DBF2; cell cycle protein kinase DBF2 [EC:2.7.11.-]
K06685  MOB1, Mats; MOB kinase activator 1
K06686  DBF20; cell cycle protein kinase DBF20 [EC:2.7.11.-]
K06687  NET1, ESC5; nucleolar protein involved in exit from mitosis
K08866  TTK, MPS1; serine/threonine-protein kinase TTK/MPS1 [EC:2.7.12.1]
K09173  RFX1_2_3; regulatory factor X 1/2/3
K09202  SWI5; regulatory protein SWI5
K10259  MET30; F-box and WD-40 domain protein MET30
K11272  MRC1; mediator of replication checkpoint protein 1
K12411  YOX1, YHP1; homeobox protein YOX1/YHP1
K12412  MCM1; pheromone receptor transcription factor
K12413  WHI5; G1-specific transcriptional repressor WHI5
K12414  TAH11; DNA replication licensing factor, required for pre-replication complex assembly
K12416  SWM1, APC13; anaphase-promoting complex subunit SWM1
K12575  SLK19; kinetochore protein SLK19
K12576  SPO12; sporulation-specific protein 12
K12577  FOB1; DNA replication fork-blocking protein FOB1
K12578  LCD1, ddc2; DNA damage checkpoint protein LCD1
K12760  CLN1; G1/S-specific cyclin CLN1
K18639  KCC4; serine/threonine-protein kinase KCC4 [EC:2.7.11.1]
K18669  DYRK2_3_4; dual specificity tyrosine-phosphorylation-regulated kinase 2/3/4 [EC:2.7.12.1]
K18679  CDR2; mitosis inducer protein kinase Cdr2 [EC:2.7.11.1]
K18680  CDR1; mitosis inducer protein kinase Cdr1 [EC:2.7.11.1]
K23458  PHO5_11_12; repressible acid phosphatase
K23469  CLB2; G2/mitotic-specific cyclin 2
Compound
C00009  Orthophosphate
C00575  3',5'-Cyclic AMP
Reference
PMID:11967159
  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
PMID:15210110
  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
PMID:15210111
  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
PMID:12464633
  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
PMID:15060174
  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
PMID:15797380
  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
PMID:18598214
  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)
DOI:10.1002/j.1460-2075.1995.tb00162.x
Reference
PMID:16285853
  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
PMID:10465783
  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
PMID:11269496
  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
PMID:10512865
  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
PMID:10213692
  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
PMID:16487340
  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
PMID:15965243
  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
PMID:15920482
  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
PMID:10469560
  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
PMID:14616062
  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
PMID:14514882
  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)
DOI:10.1002/j.1460-2075.1994.tb06359.x
Reference
PMID:11146641
  Authors
Amon A
  Title
Together until separin do us part.
  Journal
Nat Cell Biol 3:E12-4 (2001)
DOI:10.1038/35050642
Reference
PMID:10882066
  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
PMID:10811823
  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
PMID:18616603
  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
PMID:19230642
  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
PMID:19457865
  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
PMID:19021755
  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
Related
pathway
ko04010  MAPK signaling pathway
ko04020  Calcium signaling pathway
ko04120  Ubiquitin mediated proteolysis

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