M/G1 Transition (Homo sapiens)

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3, 13, 185, 2512, 23171412, 16, 23, 251812, 236, 117, 12, 23, 251814, 24520, 21102614, 243, 132, 12, 23144, 22cytosolnucleoplasmUBB(153-228) ORC3 MCM2 ORC3 Orc1:Orc4:Orc5:Orc3:Orc2:originMCM2 POLA2 MCM6 DBF4 CDC6 ORC3 MCM10 MCM4 DBF4 CDT1PSMD4 UBB(1-76) UbUBC(305-380) POLE2 MCM8 ORC2 ORC2 MCM5 origin of replication MCM10:pre-replicative complexORC6 PSMA5 origin of replication PSMD10 PSMB4 ORC5ORC3 PSMD5 UBC(457-532) ORC5 ORC5 MCM3 ORC complex bound tooriginDNA polymeraseepsilon:origincomplexDDKUBB(153-228) MCM2 origin of replication ORC3PSMF1 MCM8 ORC4 ORC6 PSMA8 UBC(457-532) ORC2 origin of replication UBC(609-684) MCM3 CDC6 ORC5 CDC6 ORC3 PSMB7 MCM5 PSMA2 MCM3 POLA1 CDK2 MCM6 ORC1 ATPPSMD1 MCM4 MCM10 CDC6PSMD3 PSMA3 MCM8 MCM7 ORC4 ORC6DNA polymeraseepsilonORC2 MCM7 PSMA4 ORC2 ORC2 ORC5 PRIM1 PSMB10 CDT1 CDT1ORC3 ORC4 MCM7 UBC(381-456) RPA1 CDC45 CDK2 UBC(229-304) origin of replication PSMC1 MCM5 POLE3 MCM2 ORC2 MCM10MCM6 ORC6 CDK2 PSMA1 ORC1 MCM8 ORC4 ORC5 origin of replication PSME2 MCM5 MCM4 UBC(533-608) CDT1:CDC6:ORC:origincomplexADPGMNN POLE3 ORC3 origin of replication SHFM1 PSME1 ORC2 MCM2 MCM5 ORC2 ORC6 CDC7 origin of replication PSMD9 ORC:origin ofreplicationORC2 CDT1 ORC4 ORC3 MCM2 ORC5 ORC4 MCM3 PSMB2 DNA polymerasealpha:primase:DNApolymerasealpha:origincomplexDBF4 p-MCM2-7MCM5 MCM8cyclin CDC7 RPA3 POLE2 MCM3 origin of replication POLE4 PSMC6 RPA4 ORC5 MCM8 origin of replication CDC7 RPA3 UBC(153-228) ORC1 origin of replication PSMB11 CDC6:ORC:origincomplexORC6 UBC(77-152) ORC3 PSMD13 ORC1 ORC3 RPS27A(1-76) RPA2 PSMB5 ORC5 ORC6 E2F2 CDKPSMD2 UBB(77-152) MCM6 POLE4 MCM2 ORC2 ORC3 MCM10 MCM10 PSMD14 POLA1 UBC(305-380) POLA2 ORC4 POLE CDK:DDK:MCM10:activepre-replicativecomplex:CDC45CDT1 Orc4:Orc5:Orc3:Orc2:originPSMC4 MCM7 ORC3 UBC(153-228) PSMB9 PSMD8 origin of replication ORC1 ORC1 UBC(533-608) PSMA7 MCM10:activepre-replicativecomplexRPA4 ORC6 Cdt1:gemininORC1MCM7 POLE2 POLE3 MCM4 MCM4 ORC1 CDC6 ORC4 26S proteasomeCDC7 ORC5 GMNN ORC1 PSMC5 ORC3 UBC(77-152) origin of replication CDC6 GMNN UBC(1-76) PSMB1 UBB(1-76) POLE4 CDC45Orc3:Orc2:originRPA1-4PSMD11 UBC(1-76) ORC5 MCM7 E2F1 CDC6 MCM8 MCM3 origin of replication MCM8 MCM2-7GMNNCDT1 ORC5 pre-replicativecomplexMCM4 MCM7 PSMB6 ORC2 origin of replication MCM7 cyclin CDC6 E2F3 cyclin CDT1 MCM6 MCM4 MCM6 PSMC3 origin of replication RPA1 CDK:DDK:MCM10:activepre-replicativecomplex:CDC45:RPA1-4ORC4 PSME3 DNA polymerasealpha:primaseORC2 ORC2 MCM8 ORC5 MCM4 POLE CDC45 cyclin Pi CDC6 UBA52(1-76) UBC(229-304) MCM3 ORC6 origin ofreplicationPSME4 geminin:ubiquitincomplexORC1 UBB(77-152) Cdt1:gemininOrc2:originorigin of replication MCM3 E2F1/2/3ORC5 CDK:DDK:MCM10:activepre-replicativecomplexORC4 UBA52(1-76) RPA2 POLE UBC(381-456) PSMB8 PRIM2 MCM5 ORC4MCM8 ORC6 PRIM1 PRIM2 MCM2 MCM6 MCM5 ORC1 ORC3 UBC(609-684) PSMD12 DBF4 ORC1 PSMA6 MCM6 ORC4 PSMD6 PSMB3 ORC6 Orc5:Orc3:Orc2:originPSMD7 PSMC2 MCM10 CDK2 ORC4 RPS27A(1-76) ORC2 12, 23820, 2112, 23, 259112, 231, 2715, 1912, 23, 2512, 23, 2512, 2312, 23


Description

Finally, progression out of mitosis and division of the cell into two daughters (cytokinesis) requires the inactivation of Cyclin B - Cdc2 by ubiquitin-dependent proteolysis of Cyclin A and B, which is regulated by a large E3 ubiquitin ligase complex known as the Anaphase Promoting Complex (APC).

The detailed annotation of the M/G1 transition will be completed in a later version of GK. View original pathway at:Reactome.</div>

Comments

Reactome-Converter 
Pathway is converted from Reactome ID: 68874
Reactome-version 
Reactome version: 65

Quality Tags

Ontology Terms

 

Bibliography

View all...
  1. Wei SJ, Williams JG, Dang H, Darden TA, Betz BL, Humble MM, Chang FM, Trempus CS, Johnson K, Cannon RE, Tennant RW.; ''Identification of a specific motif of the DSS1 protein required for proteasome interaction and p53 protein degradation.''; PubMed Europe PMC
  2. Quintana DG, Thome KC, Hou ZH, Ligon AH, Morton CC, Dutta A.; ''ORC5L, a new member of the human origin recognition complex, is deleted in uterine leiomyomas and malignant myeloid diseases.''; PubMed Europe PMC
  3. Walter J, Newport J.; ''Initiation of eukaryotic DNA replication: origin unwinding and sequential chromatin association of Cdc45, RPA, and DNA polymerase alpha.''; PubMed Europe PMC
  4. Saha P, Thome KC, Yamaguchi R, Hou Z, Weremowicz S, Dutta A.; ''The human homolog of Saccharomyces cerevisiae CDC45.''; PubMed Europe PMC
  5. Volkening M, Hoffmann I.; ''Involvement of human MCM8 in prereplication complex assembly by recruiting hcdc6 to chromatin.''; PubMed Europe PMC
  6. Ohtani K, Tsujimoto A, Ikeda M, Nakamura M.; ''Regulation of cell growth-dependent expression of mammalian CDC6 gene by the cell cycle transcription factor E2F.''; PubMed Europe PMC
  7. Ritzi M, Baack M, Musahl C, Romanowski P, Laskey RA, Knippers R.; ''Human minichromosome maintenance proteins and human origin recognition complex 2 protein on chromatin.''; PubMed Europe PMC
  8. Jiang W, Wells NJ, Hunter T.; ''Multistep regulation of DNA replication by Cdk phosphorylation of HsCdc6.''; PubMed Europe PMC
  9. Hubscher U, Maga G, Spadari S.; ''Eukaryotic DNA polymerases.''; PubMed Europe PMC
  10. Herbig U, Marlar CA, Fanning E.; ''The Cdc6 nucleotide-binding site regulates its activity in DNA replication in human cells.''; PubMed Europe PMC
  11. Yan Z, DeGregori J, Shohet R, Leone G, Stillman B, Nevins JR, Williams RS.; ''Cdc6 is regulated by E2F and is essential for DNA replication in mammalian cells.''; PubMed Europe PMC
  12. Dhar SK, Delmolino L, Dutta A.; ''Architecture of the human origin recognition complex.''; PubMed Europe PMC
  13. Zou L, Stillman B.; ''Assembly of a complex containing Cdc45p, replication protein A, and Mcm2p at replication origins controlled by S-phase cyclin-dependent kinases and Cdc7p-Dbf4p kinase.''; PubMed Europe PMC
  14. Wohlschlegel JA, Dwyer BT, Dhar SK, Cvetic C, Walter JC, Dutta A.; ''Inhibition of eukaryotic DNA replication by geminin binding to Cdt1.''; PubMed Europe PMC
  15. Li Y, Pursell ZF, Linn S.; ''Identification and cloning of two histone fold motif-containing subunits of HeLa DNA polymerase epsilon.''; PubMed Europe PMC
  16. Li CJ, DePamphilis ML.; ''Mammalian Orc1 protein is selectively released from chromatin and ubiquitinated during the S-to-M transition in the cell division cycle.''; PubMed Europe PMC
  17. Masai H, Matsui E, You Z, Ishimi Y, Tamai K, Arai K.; ''Human Cdc7-related kinase complex. In vitro phosphorylation of MCM by concerted actions of Cdks and Cdc7 and that of a criticial threonine residue of Cdc7 bY Cdks.''; PubMed Europe PMC
  18. Bell SP, Dutta A.; ''DNA replication in eukaryotic cells.''; PubMed Europe PMC
  19. Li Y, Asahara H, Patel VS, Zhou S, Linn S.; ''Purification, cDNA cloning, and gene mapping of the small subunit of human DNA polymerase epsilon.''; PubMed Europe PMC
  20. Jiang W, McDonald D, Hope TJ, Hunter T.; ''Mammalian Cdc7-Dbf4 protein kinase complex is essential for initiation of DNA replication.''; PubMed Europe PMC
  21. Kumagai H, Sato N, Yamada M, Mahony D, Seghezzi W, Lees E, Arai K, Masai H.; ''A novel growth- and cell cycle-regulated protein, ASK, activates human Cdc7-related kinase and is essential for G1/S transition in mammalian cells.''; PubMed Europe PMC
  22. Kukimoto I, Igaki H, Kanda T.; ''Human CDC45 protein binds to minichromosome maintenance 7 protein and the p70 subunit of DNA polymerase alpha.''; PubMed Europe PMC
  23. Vashee S, Simancek P, Challberg MD, Kelly TJ.; ''Assembly of the human origin recognition complex.''; PubMed Europe PMC
  24. McGarry TJ, Kirschner MW.; ''Geminin, an inhibitor of DNA replication, is degraded during mitosis.''; PubMed Europe PMC
  25. Méndez J, Stillman B.; ''Chromatin association of human origin recognition complex, cdc6, and minichromosome maintenance proteins during the cell cycle: assembly of prereplication complexes in late mitosis.''; PubMed Europe PMC
  26. Izumi M, Yanagi K, Mizuno T, Yokoi M, Kawasaki Y, Moon KY, Hurwitz J, Yatagai F, Hanaoka F.; ''The human homolog of Saccharomyces cerevisiae Mcm10 interacts with replication factors and dissociates from nuclease-resistant nuclear structures in G(2) phase.''; PubMed Europe PMC
  27. Voges D, Zwickl P, Baumeister W.; ''The 26S proteasome: a molecular machine designed for controlled proteolysis.''; PubMed Europe PMC

History

View all...
CompareRevisionActionTimeUserComment
100734view20:33, 31 October 2018ReactomeTeamreactome version 65
100278view19:10, 31 October 2018ReactomeTeamreactome version 64
99824view15:54, 31 October 2018ReactomeTeamreactome version 63
99381view14:32, 31 October 2018ReactomeTeamreactome version 62 (2nd attempt)
99081view12:38, 31 October 2018ReactomeTeamreactome version 62
93978view13:49, 16 August 2017ReactomeTeamreactome version 61
93580view11:27, 9 August 2017ReactomeTeamreactome version 61
86966view13:35, 15 July 2016MkutmonOntology Term : 'M/G1 transition pathway' added !
86686view09:24, 11 July 2016ReactomeTeamreactome version 56
83220view10:25, 18 November 2015ReactomeTeamVersion54
81613view13:09, 21 August 2015ReactomeTeamVersion53
77074view08:37, 17 July 2014ReactomeTeamFixed remaining interactions
76779view12:14, 16 July 2014ReactomeTeamFixed remaining interactions
76102view10:16, 11 June 2014ReactomeTeamRe-fixing comment source
75814view11:36, 10 June 2014ReactomeTeamReactome 48 Update
75164view14:11, 8 May 2014AnweshaFixing comment source for displaying WikiPathways description
74811view08:54, 30 April 2014ReactomeTeamNew pathway

External references

DataNodes

View all...
NameTypeDatabase referenceComment
26S proteasomeComplexR-HSA-68819 (Reactome)
ADPMetaboliteCHEBI:16761 (ChEBI)
ATPMetaboliteCHEBI:15422 (ChEBI)
CDC45 ProteinO75419 (Uniprot-TrEMBL)
CDC45ProteinO75419 (Uniprot-TrEMBL)
CDC6 ProteinQ99741 (Uniprot-TrEMBL)
CDC6:ORC:origin complexComplexR-HSA-68543 (Reactome)
CDC6ProteinQ99741 (Uniprot-TrEMBL)
CDC7 ProteinO00311 (Uniprot-TrEMBL)
CDK2 ProteinP24941 (Uniprot-TrEMBL)
CDK:DDK:MCM10:active

pre-replicative

complex:CDC45:RPA1-4
ComplexR-HSA-68568 (Reactome)
CDK:DDK:MCM10:active

pre-replicative

complex:CDC45
ComplexR-HSA-68564 (Reactome)
CDK:DDK:MCM10:active

pre-replicative

complex
ComplexR-HSA-68561 (Reactome)
CDKComplexR-HSA-68380 (Reactome)
CDT1 ProteinQ9H211 (Uniprot-TrEMBL)
CDT1:CDC6:ORC:origin complexComplexR-HSA-68544 (Reactome)
CDT1ProteinQ9H211 (Uniprot-TrEMBL)
Cdt1:gemininComplexR-HSA-156502 (Reactome)
Cdt1:gemininComplexR-HSA-68537 (Reactome)
DBF4 ProteinQ9UBU7 (Uniprot-TrEMBL)
DDKComplexR-HSA-68388 (Reactome)
DNA polymerase

alpha:primase:DNA polymerase alpha:origin

complex
ComplexR-HSA-68510 (Reactome)
DNA polymerase alpha:primaseComplexR-HSA-68507 (Reactome)
DNA polymerase

epsilon:origin

complex
ComplexR-HSA-68485 (Reactome)
DNA polymerase epsilonComplexR-HSA-68483 (Reactome)
E2F1 ProteinQ01094 (Uniprot-TrEMBL)
E2F1/2/3ComplexR-HSA-68640 (Reactome)
E2F2 ProteinQ14209 (Uniprot-TrEMBL)
E2F3 ProteinO00716 (Uniprot-TrEMBL)
GMNN ProteinO75496 (Uniprot-TrEMBL)
GMNNProteinO75496 (Uniprot-TrEMBL)
MCM10 ProteinQ7L590 (Uniprot-TrEMBL)
MCM10:active

pre-replicative

complex
ComplexR-HSA-156564 (Reactome)
MCM10:pre-replicative complexComplexR-HSA-68560 (Reactome)
MCM10ProteinQ7L590 (Uniprot-TrEMBL)
MCM2 ProteinP49736 (Uniprot-TrEMBL)
MCM2-7ComplexR-HSA-68558 (Reactome)
MCM3 ProteinP25205 (Uniprot-TrEMBL)
MCM4 ProteinP33991 (Uniprot-TrEMBL)
MCM5 ProteinP33992 (Uniprot-TrEMBL)
MCM6 ProteinQ14566 (Uniprot-TrEMBL)
MCM7 ProteinP33993 (Uniprot-TrEMBL)
MCM8 ProteinQ9UJA3 (Uniprot-TrEMBL)
MCM8ProteinQ9UJA3 (Uniprot-TrEMBL)
ORC complex bound to originComplexR-HSA-176958 (Reactome)
ORC1 ProteinQ13415 (Uniprot-TrEMBL)
ORC1ProteinQ13415 (Uniprot-TrEMBL)
ORC2 ProteinQ13416 (Uniprot-TrEMBL)
ORC3 ProteinQ9UBD5 (Uniprot-TrEMBL)
ORC3ProteinQ9UBD5 (Uniprot-TrEMBL)
ORC4 ProteinO43929 (Uniprot-TrEMBL)
ORC4ProteinO43929 (Uniprot-TrEMBL)
ORC5 ProteinO43913 (Uniprot-TrEMBL)
ORC5ProteinO43913 (Uniprot-TrEMBL)
ORC6 ProteinQ9Y5N6 (Uniprot-TrEMBL)
ORC6ProteinQ9Y5N6 (Uniprot-TrEMBL)
ORC:origin of replicationComplexR-HSA-68540 (Reactome)
Orc1:Orc4:Orc5:Orc3:Orc2:originComplexR-HSA-68592 (Reactome)
Orc2:originComplexR-HSA-68511 (Reactome)
Orc3:Orc2:originComplexR-HSA-68514 (Reactome)
Orc4:Orc5:Orc3:Orc2:originComplexR-HSA-68520 (Reactome)
Orc5:Orc3:Orc2:originComplexR-HSA-68517 (Reactome)
POLA1 ProteinP09884 (Uniprot-TrEMBL)
POLA2 ProteinQ14181 (Uniprot-TrEMBL)
POLE ProteinQ07864 (Uniprot-TrEMBL)
POLE2 ProteinP56282 (Uniprot-TrEMBL)
POLE3 ProteinQ9NRF9 (Uniprot-TrEMBL)
POLE4 ProteinQ9NR33 (Uniprot-TrEMBL)
PRIM1 ProteinP49642 (Uniprot-TrEMBL)
PRIM2 ProteinP49643 (Uniprot-TrEMBL)
PSMA1 ProteinP25786 (Uniprot-TrEMBL)
PSMA2 ProteinP25787 (Uniprot-TrEMBL)
PSMA3 ProteinP25788 (Uniprot-TrEMBL)
PSMA4 ProteinP25789 (Uniprot-TrEMBL)
PSMA5 ProteinP28066 (Uniprot-TrEMBL)
PSMA6 ProteinP60900 (Uniprot-TrEMBL)
PSMA7 ProteinO14818 (Uniprot-TrEMBL)
PSMA8 ProteinQ8TAA3 (Uniprot-TrEMBL)
PSMB1 ProteinP20618 (Uniprot-TrEMBL)
PSMB10 ProteinP40306 (Uniprot-TrEMBL)
PSMB11 ProteinA5LHX3 (Uniprot-TrEMBL)
PSMB2 ProteinP49721 (Uniprot-TrEMBL)
PSMB3 ProteinP49720 (Uniprot-TrEMBL)
PSMB4 ProteinP28070 (Uniprot-TrEMBL)
PSMB5 ProteinP28074 (Uniprot-TrEMBL)
PSMB6 ProteinP28072 (Uniprot-TrEMBL)
PSMB7 ProteinQ99436 (Uniprot-TrEMBL)
PSMB8 ProteinP28062 (Uniprot-TrEMBL)
PSMB9 ProteinP28065 (Uniprot-TrEMBL)
PSMC1 ProteinP62191 (Uniprot-TrEMBL)
PSMC2 ProteinP35998 (Uniprot-TrEMBL)
PSMC3 ProteinP17980 (Uniprot-TrEMBL)
PSMC4 ProteinP43686 (Uniprot-TrEMBL)
PSMC5 ProteinP62195 (Uniprot-TrEMBL)
PSMC6 ProteinP62333 (Uniprot-TrEMBL)
PSMD1 ProteinQ99460 (Uniprot-TrEMBL)
PSMD10 ProteinO75832 (Uniprot-TrEMBL)
PSMD11 ProteinO00231 (Uniprot-TrEMBL)
PSMD12 ProteinO00232 (Uniprot-TrEMBL)
PSMD13 ProteinQ9UNM6 (Uniprot-TrEMBL)
PSMD14 ProteinO00487 (Uniprot-TrEMBL)
PSMD2 ProteinQ13200 (Uniprot-TrEMBL)
PSMD3 ProteinO43242 (Uniprot-TrEMBL)
PSMD4 ProteinP55036 (Uniprot-TrEMBL)
PSMD5 ProteinQ16401 (Uniprot-TrEMBL)
PSMD6 ProteinQ15008 (Uniprot-TrEMBL)
PSMD7 ProteinP51665 (Uniprot-TrEMBL)
PSMD8 ProteinP48556 (Uniprot-TrEMBL)
PSMD9 ProteinO00233 (Uniprot-TrEMBL)
PSME1 ProteinQ06323 (Uniprot-TrEMBL)
PSME2 ProteinQ9UL46 (Uniprot-TrEMBL)
PSME3 ProteinP61289 (Uniprot-TrEMBL)
PSME4 ProteinQ14997 (Uniprot-TrEMBL)
PSMF1 ProteinQ92530 (Uniprot-TrEMBL)
Pi MetaboliteCHEBI:18367 (ChEBI)
RPA1 ProteinP27694 (Uniprot-TrEMBL)
RPA1-4ComplexR-HSA-68567 (Reactome)
RPA2 ProteinP15927 (Uniprot-TrEMBL)
RPA3 ProteinP35244 (Uniprot-TrEMBL)
RPA4 ProteinQ13156 (Uniprot-TrEMBL)
RPS27A(1-76) ProteinP62979 (Uniprot-TrEMBL)
SHFM1 ProteinP60896 (Uniprot-TrEMBL)
UBA52(1-76) ProteinP62987 (Uniprot-TrEMBL)
UBB(1-76) ProteinP0CG47 (Uniprot-TrEMBL)
UBB(153-228) ProteinP0CG47 (Uniprot-TrEMBL)
UBB(77-152) ProteinP0CG47 (Uniprot-TrEMBL)
UBC(1-76) ProteinP0CG48 (Uniprot-TrEMBL)
UBC(153-228) ProteinP0CG48 (Uniprot-TrEMBL)
UBC(229-304) ProteinP0CG48 (Uniprot-TrEMBL)
UBC(305-380) ProteinP0CG48 (Uniprot-TrEMBL)
UBC(381-456) ProteinP0CG48 (Uniprot-TrEMBL)
UBC(457-532) ProteinP0CG48 (Uniprot-TrEMBL)
UBC(533-608) ProteinP0CG48 (Uniprot-TrEMBL)
UBC(609-684) ProteinP0CG48 (Uniprot-TrEMBL)
UBC(77-152) ProteinP0CG48 (Uniprot-TrEMBL)
UbComplexR-HSA-113595 (Reactome)
cyclin R-HSA-68379 (Reactome)
geminin:ubiquitin complexComplexR-HSA-68585 (Reactome)
origin of replicationR-ALL-68419 (Reactome)
origin of replication R-ALL-68419 (Reactome)
p-MCM2-7ComplexR-HSA-68569 (Reactome)
pre-replicative complexComplexR-HSA-68559 (Reactome)

Annotated Interactions

View all...
SourceTargetTypeDatabase referenceComment
26S proteasomemim-catalysisR-HSA-68825 (Reactome)
ADPArrowR-HSA-68954 (Reactome)
ATPR-HSA-68954 (Reactome)
CDC45R-HSA-68917 (Reactome)
CDC6:ORC:origin complexArrowR-HSA-68688 (Reactome)
CDC6:ORC:origin complexR-HSA-68826 (Reactome)
CDC6ArrowR-HSA-68637 (Reactome)
CDC6R-HSA-68688 (Reactome)
CDK:DDK:MCM10:active

pre-replicative

complex:CDC45:RPA1-4
ArrowR-HSA-68914 (Reactome)
CDK:DDK:MCM10:active

pre-replicative

complex:CDC45:RPA1-4
ArrowR-HSA-68916 (Reactome)
CDK:DDK:MCM10:active

pre-replicative

complex:CDC45:RPA1-4
ArrowR-HSA-68960 (Reactome)
CDK:DDK:MCM10:active

pre-replicative

complex:CDC45
ArrowR-HSA-68917 (Reactome)
CDK:DDK:MCM10:active

pre-replicative

complex:CDC45
R-HSA-68916 (Reactome)
CDK:DDK:MCM10:active

pre-replicative

complex
ArrowR-HSA-68918 (Reactome)
CDK:DDK:MCM10:active

pre-replicative

complex
R-HSA-68917 (Reactome)
CDKR-HSA-68918 (Reactome)
CDT1:CDC6:ORC:origin complexArrowR-HSA-68826 (Reactome)
CDT1:CDC6:ORC:origin complexR-HSA-68849 (Reactome)
CDT1ArrowR-HSA-68712 (Reactome)
CDT1ArrowR-HSA-68940 (Reactome)
CDT1R-HSA-68826 (Reactome)
CDT1R-HSA-69299 (Reactome)
Cdt1:gemininArrowR-HSA-69299 (Reactome)
Cdt1:gemininR-HSA-68712 (Reactome)
DDKR-HSA-68918 (Reactome)
DDKmim-catalysisR-HSA-68954 (Reactome)
DNA polymerase

alpha:primase:DNA polymerase alpha:origin

complex
ArrowR-HSA-68914 (Reactome)
DNA polymerase alpha:primaseR-HSA-68914 (Reactome)
DNA polymerase

epsilon:origin

complex
ArrowR-HSA-68960 (Reactome)
DNA polymerase

epsilon:origin

complex
R-HSA-68914 (Reactome)
DNA polymerase epsilonR-HSA-68960 (Reactome)
E2F1/2/3ArrowR-HSA-68637 (Reactome)
GMNNR-HSA-69299 (Reactome)
MCM10:active

pre-replicative

complex
ArrowR-HSA-68940 (Reactome)
MCM10:active

pre-replicative

complex
R-HSA-68918 (Reactome)
MCM10:pre-replicative complexArrowR-HSA-68919 (Reactome)
MCM10:pre-replicative complexR-HSA-68940 (Reactome)
MCM10R-HSA-68919 (Reactome)
MCM2-7R-HSA-68849 (Reactome)
MCM2-7R-HSA-68954 (Reactome)
MCM8R-HSA-176973 (Reactome)
ORC complex bound to originArrowR-HSA-68615 (Reactome)
ORC complex bound to originR-HSA-176973 (Reactome)
ORC1R-HSA-68611 (Reactome)
ORC3R-HSA-68595 (Reactome)
ORC4R-HSA-68610 (Reactome)
ORC5R-HSA-68603 (Reactome)
ORC6R-HSA-68615 (Reactome)
ORC:origin of replicationArrowR-HSA-176973 (Reactome)
ORC:origin of replicationR-HSA-68688 (Reactome)
Orc1:Orc4:Orc5:Orc3:Orc2:originArrowR-HSA-68611 (Reactome)
Orc1:Orc4:Orc5:Orc3:Orc2:originR-HSA-68615 (Reactome)
Orc2:originR-HSA-68595 (Reactome)
Orc3:Orc2:originArrowR-HSA-68595 (Reactome)
Orc3:Orc2:originR-HSA-68603 (Reactome)
Orc4:Orc5:Orc3:Orc2:originArrowR-HSA-68610 (Reactome)
Orc4:Orc5:Orc3:Orc2:originR-HSA-68611 (Reactome)
Orc5:Orc3:Orc2:originArrowR-HSA-68603 (Reactome)
Orc5:Orc3:Orc2:originR-HSA-68610 (Reactome)
R-HSA-176973 (Reactome) The MCM2-7 complex, an essential component of the pre-replication complex, recruits CDC6 and CDT1 proteins to the origin. MCM8, another member of the MCM family has been found to bind to chromatin during early G1 phase. MCM8 interacts specifically with the ORC2 protein.
R-HSA-68595 (Reactome) At the beginning of this reaction, 1 molecule of 'Orc2:origin', and 1 molecule of 'Orc3' are present. At the end of this reaction, 1 molecule of 'Orc3:Orc2:origin' is present.

This reaction takes place in the 'nucleus'.

R-HSA-68603 (Reactome) At the beginning of this reaction, 1 molecule of 'Orc3:Orc2:origin', and 1 molecule of 'Orc5' are present. At the end of this reaction, 1 molecule of 'Orc5:Orc3:Orc2:origin' is present.

This reaction takes place in the 'nucleus'.

R-HSA-68610 (Reactome) At the beginning of this reaction, 1 molecule of 'Orc4', and 1 molecule of 'Orc5:Orc3:Orc2:origin' are present. At the end of this reaction, 1 molecule of 'Orc4:Orc5:Orc3:Orc2:origin' is present.

This reaction takes place in the 'nucleus'.

R-HSA-68611 (Reactome) At the beginning of this reaction, 1 molecule of 'Orc4:Orc5:Orc3:Orc2:origin', and 1 molecule of 'Orc1' are present. At the end of this reaction, 1 molecule of 'Orc1:Orc4:Orc5:Orc3:Orc2:origin' is present.

This reaction takes place in the 'nucleus'.

R-HSA-68615 (Reactome) At the beginning of this reaction, 1 molecule of 'Orc1:Orc4:Orc5:Orc3:Orc2:origin', and 1 molecule of 'Orc6' are present. At the end of this reaction, 1 molecule of 'ORC complex bound to origin' is present.

This reaction takes place in the 'nucleus'.

R-HSA-68637 (Reactome) At the end of this reaction, 1 molecule of 'Cdc6' is present.



R-HSA-68688 (Reactome) At the beginning of this reaction, 1 molecule of 'ORC:origin', and 1 molecule of 'CDC6' are present. At the end of this reaction, 1 molecule of 'CDC6:ORC:origin complex' is present.

This reaction takes place in the 'nucleus'.

R-HSA-68712 (Reactome) At the beginning of this reaction, 1 molecule of 'ubiquitin', and 1 molecule of 'Cdt1:geminin' are present. At the end of this reaction, 1 molecule of 'geminin:ubiquitin complex', and 1 molecule of 'Cdt1' are present.

This reaction takes place in the 'cytosol'.

R-HSA-68825 (Reactome) At the beginning of this reaction, 1 molecule of 'geminin:ubiquitin complex' is present. At the end of this reaction, 1 molecule of 'ubiquitin' is present.

This reaction takes place in the 'cytosol' and is mediated by the 'endopeptidase activity' of '26S proteasome'.

R-HSA-68826 (Reactome) At the beginning of this reaction, 1 molecule of 'CDT1', and 1 molecule of 'CDC6:ORC:origin complex' are present. At the end of this reaction, 1 molecule of 'CDT1:CDC6:ORC:origin complex' is present.

This reaction takes place in the 'nucleus'.

R-HSA-68849 (Reactome) Genetic studies in S. cerevisiae indicate that wild-type Cdc6 function is required for correctly timed loading of Mcm2-7 onto ORC. Biochemical studies indicate that the human and Xenopus Cdc6 proteins likewise are required for Mcm2-7 loading, and that they are ATPase switches. Specifically, Cdc6 may function as a clamp loader, assembling Mcm2-7 onto DNA in an ATP-dependent reaction. All known Cdc6 proteins have the Walker A and Walker B sequence motifs characteristic of the AAA+ superfamily of ATPases. As expected for an AAA+ protein, human Cdc6 binds and slowly hydrolyzes ATP in vitro. ATP hydrolysis was disrupted by mutations of the Walker B motif, while both binding and hydrolysis were disrupted by Walker A mutations. Microinjection of either mutant protein into HeLa cells blocked their progression through S phase. Both wild-type and mutant proteins can dimerize in vitro, and studies with Xenopus egg extracts suggest that Cdc6 functions in vivo as a dimer or larger multimer. In Xenopus extracts depleted of Cdc6 and reconstituted with either mutant protein, recruitment of Mcm2-7 to chromatin failed.
R-HSA-68914 (Reactome) DNA polymerase alpha:primase is comprised of four subunits, p180, p70, p58, and p49. The two primase subunits, p58 and p49, form a tight complex. The p49 subunit contains the DNA primase activity and one role of p58 appears to be tethering p49 to p180, the DNA polymerase catalytic subunit. The fourth subunit, p70, binds p180 and may tether the DNA polymerase alpha:primase complex to Cdc45.
R-HSA-68916 (Reactome) After pre-RC assembly and Cdc45 association with the origin of replication, Replication Protein A (RPA) also associates with chromatin. RPA is a heterotrimeric complex containing p70, p34, and p11 subunits, and also is required for DNA recombination and DNA repair. The p70 subunit of RPA binds to the primase subunits of Pol alpha:primase. The p70 and p34 subunits of RPA are phosphorylated in a cell cycle-dependent manner. RPA is a single-strand DNA (ssDNA) binding protein and its association with chromatin at this stage suggests that DNA is partially unwound. This suggestion has been confirmed by detection of ssDNA in budding yeast origins of replication using chemical methods.
R-HSA-68917 (Reactome) Once the Mcm2-7 complex has been assembled onto the origin of replication, the next step is the assembly of Cdc45, an essential replication protein, in late G1. The assembly of Cdc45 onto origins of replication forms a complex distinct from the pre-replicative complex, sometimes called the pre-initiation complex. The assembly of Cdc45 onto origins correlates with the time of initiation. Like the Mcm2-7 proteins, Cdc45 binds specifically to origins in the G1 phase of the cell cycle and then to non-origin DNA during S phase and is therefore thought to travel with the replication fork. Indeed, S. cerevisiae Cdc45 is required for DNA replication elongation as well as replication initiation. Cdc45 is required for the association of alpha DNA polymerase:primase with chromatin. Based on this observation and the observation that in S. cerevisiae, cCdc45 has been found in large complexes with some components of Mcm2-7 complex, it has been suggested that Cdc45 plays a scaffolding role at the replication fork, coupling Pol-alpha:primase to the replication fork through the helicase. Association of Cdc45 with origin DNA is regulated in the cell cycle and its association is dependent on the activity of cyclin-dependent kinases but not the Cdc7/Dbf4 kinase. In Xenopus egg extracts, association of Cdc45 with chromatin is dependent on Xmus101. TopBP1, the human homolog of Xmus1, is essential for DNA replication and interacts with DNA polymerase epsilon, one of the polymerases involved in replicating the genome. TopBP1 homologs have been found in S. cerevisiae and S. pombe. Sld3, an additional protein required for Cdc45 association with chromatin in S. cerevisiae and S. pombe, has no known human homolog.
R-HSA-68918 (Reactome) At the beginning of this reaction, 1 molecule of 'Mcm10:active pre-replicative complex', 1 molecule of 'DDK', and 1 molecule of 'CDK' are present. At the end of this reaction, 1 molecule of 'CDK:DDK:Mcm10:pre-replicative complex' is present.

This reaction takes place in the 'nucleus'.

R-HSA-68919 (Reactome) MCM10 is required for human DNA replication. In S. cerevisiae, Mcm10, like Mcm2-7, is required for minichromosome maintenance, but Mcm10 has no sequence homology with these other proteins (Merchant et al., 1997). Genetic studies have demonstrated that Mcm10 is required for DNA replication in S. pombe (Aves et al., 1998) and S. cerevisiae cells (Homesley et al., 2000) and immunodepletion of XlMcm10 interferes with DNA replication in Xenopus egg extracts (Wohlschlegel et al., 2002). Human Mcm10 interacts with chromatin in G1 phase and then dissociates during G2 phase. In S. cerevisiae, Mcm10 has been shown to localize to origins during G1 (Ricke and Bielinsky, 2004), and it may stabilize the association of Mcm2-7 with the pre-replicative complex (Sawyer et al., 2004). This timing of association is consistent with studies that demonstrate that, in Xenopus egg extracts, Mcm10 is required for association of Cdc45, but not Mcm2-7 with chromatin. Biochemical evidence that Mcm10 plays a direct role in the activation of the pre-replicative complex includes the requirement for SpMcm10 in the phosphorylation of the Mcm2-7 complex by DDK (Lee et al., 2004) and the fact that SpMcm10 binds and stimulates DNA polymerase alpha activity (Fien et al., 2004).
R-HSA-68940 (Reactome) At the beginning of this reaction, 1 molecule of 'Mcm10:pre-replicative complex' is present. At the end of this reaction, 1 molecule of 'Mcm10:active pre-replicative complex', and 1 molecule of 'CDT1' are present.

This reaction takes place in the 'nucleus'.

R-HSA-68954 (Reactome) At the beginning of this reaction, 1 molecule of 'Mcm2-7 complex', and 1 molecule of 'ATP' are present. At the end of this reaction, 1 molecule of 'phosphorylated Mcm2-7 complex', and 1 molecule of 'ADP' are present.

This reaction takes place in the 'nucleus' and is mediated by the 'kinase activity' of 'DDK'.

R-HSA-68960 (Reactome) At the beginning of this reaction, 1 molecule of 'origin of replication', and 1 molecule of 'DNA polymerase epsilon' are present. At the end of this reaction, 1 molecule of 'DNA polymerase epsilon:origin complex' is present.



R-HSA-69299 (Reactome) At the beginning of this reaction, 1 molecule of 'geminin', and 1 molecule of 'CDT1' are present. At the end of this reaction, 1 molecule of 'Cdt1:geminin' is present.

This reaction takes place in the 'nucleoplasm'.

RPA1-4R-HSA-68916 (Reactome)
UbArrowR-HSA-68825 (Reactome)
UbR-HSA-68712 (Reactome)
geminin:ubiquitin complexArrowR-HSA-68712 (Reactome)
geminin:ubiquitin complexR-HSA-68825 (Reactome)
origin of replicationR-HSA-68960 (Reactome)
p-MCM2-7ArrowR-HSA-68954 (Reactome)
pre-replicative complexArrowR-HSA-68849 (Reactome)
pre-replicative complexR-HSA-68919 (Reactome)

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