Synthesis of DNA (Homo sapiens)

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3, 9, 11, 17, 32...3720233823, 381413372393710, 17, 3415, 257145, 408, 12, 17, 22, 28...1, 1962318, 21, 373cytosolnucleoplasmPRIM2 GINS2UBC(533-608) origin of replication UBC(229-304) UBA52(1-76) PRIM1 UBA52(1-76) MCM6 CDC27 ANAPC10 POLA2 GINS3 PSME2 UTP PSMB9 origin of replication PCNA UBC(229-304) MCM5 PSMF1 PSMC3 CTP CDC26 DNA polymerasealpha:primaseANAPC15 RFC1 PRIM1 RNA primer:originduplex:DNApolymerasealpha:primasecomplexRNA primer RNA primer-DNAprimer:originduplexATPMCM2 GMPDNA Polymerase deltatetramerRFC3 POLD4 origin of replication PolyUb,p-S,T-ORC1RPA3 PSMD6 UbDNA primer ATPANAPC1 UBC(381-456) PSMA6 PSMD12 MCM4 PSMD7 PSMD8 MCM3 POLA2 Okazaki fragmentPOLA1 origin of replication RFC4 CCNA:p-T160-CDK2POLD4 MCM5 CCNA2 ADPADPPOLD2 POLE UBC(457-532) PRIM1 UbMCM5PRIM1 PRIM1 RNA primer Okazaki fragment Processivecomplex:nicked DNAfrom adjacentOkazaki fragmentsPSMC1 PSME1 RFC3 POLD1 MCM2UBC(381-456) PSMA8 DNA polymeraseepsilonPRIM1 Remaining Flap PRIM2 ANAPC11 RFC1 UBC(609-684) POLD3 PSMD4 ORC5 PSMB8 ORC6 POLD1 MCM3 POLA1 Mcm4,6,7 complexCMPPOLD2 PSMD2 PCNA FEN1MCM2 Okazaki fragment PCNA RPA2 p-T160-CDK2 POLE4 UBA52(1-76) CCNA:p-T160-CDK2,CCNE:p-T160-CDK2ANAPC2 POLD2 ORC2 PSMD11 ORC4 PSMA5 Replication ForkRFC5 POLD4 POLA2 PSMB5 Processivecomplex:Okazakifragment:Flap:RPAheterotrimer:dna2MCM8 POLD4 Processivecomplex:Okazakifragment complexRNA primer PRIM2 PSMA4 MCM2 POLA2 UBC(229-304) origin of replication FZR1 POLA1 CDT1 PRIM2 GINS2 DNA2MCM5 RNA primer CDC45 UBC(153-228) CDC6 POLA1 GINS4 UBC(609-684) POLA2 POLA1 DNA primer origin of replication Processivecomplex:Okazakifragment:FlapSHFM1 RNA primer DNA primer POLA2 dCTPCCNE1 PSMC6 UBB(153-228) PRIM1 POLD3 PSME4 ORC5 PRIM1 POLD4 MCM2-7PCNA POLA2 RFC5 GINS1 CUL1 POLA2 PSMD10 AMPUBE2S Unwinding complex atreplication forkPSMD3 ADPFlap PRIM1 ATPPOLA1 MCM7 POLE2 CDC6 ANAPC4 MCM6 origin of replication DNA primer UBB(1-76) UBB(77-152) MCM6 POLA1 origin of replication p-CDC6PRIM2 POLA2 UBC(1-76) RFCHeteropentamer:RNAprimer-DNAprimer:originduplexPSMB2 ATPMCM8RPA1 MCM7 origin of replication MCM6 UBC(153-228) dATPDNA primer p-CDC6RNA primer Processivecomplex:Okazakifragments:RemainingFlapPSMA1 RNA primer-DNAprimer:originduplex:PCNAMCM3 RFCHeteropentamer:RNAprimer-DNAprimer:originduplex:PCNAhomotrimerRNA primer CDC45RPA2 MCM4 POLD2 POLD3 ORC3 PRIM2 POLA1 PSMA3 PCNA UBC(533-608) origin of replication CDC6 RPA3 phospho-APC/C:Cdh1complexPOLD3 MCM8 DNA primer POLD1 MCM4 RNA primer UBB(153-228) MCM5 POLD4 PSMB7 Processivecomplex:Okazakifragment:Flap:RPAheterotrimerUBC(1-76) POLD3 RFC2 dTTPPOLA1 PSMB3 POLD1 UBB(77-152) POLE2 MCM7 PRIM2 MCM3POLE3 Okazaki fragment Flap POLA1 CCNA2 UBC(305-380) PSMD13 UBB(153-228) ligated okazakifragmentProcessive complexpre-replicativecomplexPOLE PSMD14 PRIM2 Flap UBE2E1 RFC HeteropentamerUBC(457-532) POLA2 Okazaki fragment GINS complexMCM6 p-T160-CDK2 GINS4RFC4 PSME3 DNA primer ubiquitinated Cdc6PRIM1 POLD3 PSMD1 ORC4 PRIM2 RFC1 UBC(609-684) POLD1 PSMB6 UBB(1-76) Replication Fork PSMC5 PRIM2 POLD2 RBX1 UBB(77-152) UBB(1-76) CDC6PCNA MCM7 p-S,T-ORC1RPA3 NTPGINS1 PSMB1 RNA primer ORC3 Okazaki fragment minus Flap MCM4 RNA primer POLD4 RNA primer RPA1 PSMA2 UBC(1-76) DNA2 UBC(153-228) PRIM1 POLD1 GINS4 CDT1 PSMB4 POLD1 Unwound forkPSMB10 POLA2 PRIM1 POLE3 origin of replication CCNE2 UBC(457-532) MCM2 CDC16 POLA1 ANAPC7 GINS1PCNA homotrimerorigin of replication pre-replicativecomplex(Orc1-minus)PSMA7 POLD3 POLA1 SKP2 PSMD9 UBC(305-380) DNA primer POLD1 ORC1 Okazaki fragment RPA1 RFC5 DNA polymerasealpha:primase:DNApolymerasealpha:origincomplexSCF(SKP2) complexPSMC2 UBC(77-152) UBC(77-152) CDC23 PSMC4 PRIM1 SKP1 MCM4 RFC2 GINS2 26S proteasomeORC6 RPA heterotrimerCCNA1 UBC(77-152) UBC(305-380) PSMB11 UBC(381-456) POLD2 RPS27A(1-76) GTP RFC4 RPA2 RPS27A(1-76) ANAPC16 DNA primer POLA1 PRIM2 POLD2 origin of replication RPS27A(1-76) PRIM2 PCNA MCM3 PSMD5 POLD2 RFC3 MCM7 CCNA1 PCNA POLA2 DNA primer PCNA DNA primer origin of replication GINS3LIG1POLE4 POLA2 PCNA RNA primer POLA2 GINS3 POLA1 ORC2 ATP origin of replication ANAPC5 POLD4 UBC(533-608) PolyUb,p-S,T-ORC1PRIM1 PRIM2 RFC2 UMPPOLD3 dGTPUBE2D1 PRIM2 UBE2C 16, 314, 262633301327, 2924


The actual synthesis of DNA occurs in the S phase of the cell cycle. This includes the initiation of DNA replication, when the first nucleotide of the new strand is laid down during the synthesis of the primer. The DNA replication preinitiation events begin in late M or early G1 phase. View original pathway at Reactome.


Pathway is converted from Reactome ID: 69239
Reactome version: 74

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Ontology Terms



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  1. Tsurimoto T, Melendy T, Stillman B.; ''Sequential initiation of lagging and leading strand synthesis by two different polymerase complexes at the SV40 DNA replication origin.''; PubMed Europe PMC Scholia
  2. Wang TS, Hu SZ, Korn D.; ''DNA primase from KB cells. Characterization of a primase activity tightly associated with immunoaffinity-purified DNA polymerase-alpha.''; PubMed Europe PMC Scholia
  3. Bambara RA, Murante RS, Henricksen LA.; ''Enzymes and reactions at the eukaryotic DNA replication fork.''; PubMed Europe PMC Scholia
  4. Voges D, Zwickl P, Baumeister W.; ''The 26S proteasome: a molecular machine designed for controlled proteolysis.''; PubMed Europe PMC Scholia
  5. Sato M, Gotow T, You Z, Komamura-Kohno Y, Uchiyama Y, Yabuta N, Nojima H, Ishimi Y.; ''Electron microscopic observation and single-stranded DNA binding activity of the Mcm4,6,7 complex.''; PubMed Europe PMC Scholia
  6. Chang LM, Rafter E, Augl C, Bollum FJ.; ''Purification of a DNA polymerase-DNA primase complex from calf thymus glands.''; PubMed Europe PMC Scholia
  7. Kamada K, Kubota Y, Arata T, Shindo Y, Hanaoka F.; ''Structure of the human GINS complex and its assembly and functional interface in replication initiation.''; PubMed Europe PMC Scholia
  8. Lee MY, Tan CK, So AG, Downey KM.; ''Purification of deoxyribonucleic acid polymerase delta from calf thymus: partial characterization of physical properties.''; PubMed Europe PMC Scholia
  9. Waga S, Bauer G, Stillman B.; ''Reconstitution of complete SV40 DNA replication with purified replication factors.''; PubMed Europe PMC Scholia
  10. Mossi R, Keller RC, Ferrari E, Hübscher U.; ''DNA polymerase switching: II. Replication factor C abrogates primer synthesis by DNA polymerase alpha at a critical length.''; PubMed Europe PMC Scholia
  11. Nethanel T, Zlotkin T, Kaufmann G.; ''Assembly of simian virus 40 Okazaki pieces from DNA primers is reversibly arrested by ATP depletion.''; PubMed Europe PMC Scholia
  12. Zhang SJ, Zeng XR, Zhang P, Toomey NL, Chuang RY, Chang LS, Lee MY.; ''A conserved region in the amino terminus of DNA polymerase delta is involved in proliferating cell nuclear antigen binding.''; PubMed Europe PMC Scholia
  13. Petersen BO, Wagener C, Marinoni F, Kramer ER, Melixetian M, Lazzerini Denchi E, Gieffers C, Matteucci C, Peters JM, Helin K.; ''Cell cycle- and cell growth-regulated proteolysis of mammalian CDC6 is dependent on APC-CDH1.''; PubMed Europe PMC Scholia
  14. Jiang W, Wells NJ, Hunter T.; ''Multistep regulation of DNA replication by Cdk phosphorylation of HsCdc6.''; PubMed Europe PMC Scholia
  15. Harrington JJ, Lieber MR.; ''The characterization of a mammalian DNA structure-specific endonuclease.''; PubMed Europe PMC Scholia
  16. Hubscher U, Maga G, Spadari S.; ''Eukaryotic DNA polymerases.''; PubMed Europe PMC Scholia
  17. Tsurimoto T, Stillman B.; ''Replication factors required for SV40 DNA replication in vitro. II. Switching of DNA polymerase alpha and delta during initiation of leading and lagging strand synthesis.''; PubMed Europe PMC Scholia
  18. Maga G, Villani G, Tillement V, Stucki M, Locatelli GA, Frouin I, Spadari S, Hübscher U.; ''Okazaki fragment processing: modulation of the strand displacement activity of DNA polymerase delta by the concerted action of replication protein A, proliferating cell nuclear antigen, and flap endonuclease-1.''; PubMed Europe PMC Scholia
  19. Mossi R, Hübscher U.; ''Clamping down on clamps and clamp loaders--the eukaryotic replication factor C.''; PubMed Europe PMC Scholia
  20. Podust VN, Tiwari N, Stephan S, Fanning E.; ''Replication factor C disengages from proliferating cell nuclear antigen (PCNA) upon sliding clamp formation, and PCNA itself tethers DNA polymerase delta to DNA.''; PubMed Europe PMC Scholia
  21. Podust VN, Podust LM, Müller F, Hübscher U.; ''DNA polymerase delta holoenzyme: action on single-stranded DNA and on double-stranded DNA in the presence of replicative DNA helicases.''; PubMed Europe PMC Scholia
  22. Burgers PM.; ''Saccharomyces cerevisiae replication factor C. II. Formation and activity of complexes with the proliferating cell nuclear antigen and with DNA polymerases delta and epsilon.''; PubMed Europe PMC Scholia
  23. Méndez J, Zou-Yang XH, Kim SY, Hidaka M, Tansey WP, Stillman B.; ''Human origin recognition complex large subunit is degraded by ubiquitin-mediated proteolysis after initiation of DNA replication.''; PubMed Europe PMC Scholia
  24. Zheng N, Schulman BA, Song L, Miller JJ, Jeffrey PD, Wang P, Chu C, Koepp DM, Elledge SJ, Pagano M, Conaway RC, Conaway JW, Harper JW, Pavletich NP.; ''Structure of the Cul1-Rbx1-Skp1-F boxSkp2 SCF ubiquitin ligase complex.''; PubMed Europe PMC Scholia
  25. Harrington JJ, Lieber MR.; ''DNA structural elements required for FEN-1 binding.''; PubMed Europe PMC Scholia
  26. 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 Scholia
  27. 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 Scholia
  28. Hindges R, Hübscher U.; ''DNA polymerase delta, an essential enzyme for DNA transactions.''; PubMed Europe PMC Scholia
  29. Li Y, Pursell ZF, Linn S.; ''Identification and cloning of two histone fold motif-containing subunits of HeLa DNA polymerase epsilon.''; PubMed Europe PMC Scholia
  30. Plafker SM, Plafker KS, Weissman AM, Macara IG.; ''Ubiquitin charging of human class III ubiquitin-conjugating enzymes triggers their nuclear import.''; PubMed Europe PMC Scholia
  31. Zhang Y, Baranovskiy AG, Tahirov TH, Pavlov YI.; ''The C-terminal domain of the DNA polymerase catalytic subunit regulates the primase and polymerase activities of the human DNA polymerase α-primase complex.''; PubMed Europe PMC Scholia
  32. Brown WC, Campbell JL.; ''Interaction of proliferating cell nuclear antigen with yeast DNA polymerase delta.''; PubMed Europe PMC Scholia
  33. Pacek M, Tutter AV, Kubota Y, Takisawa H, Walter JC.; ''Localization of MCM2-7, Cdc45, and GINS to the site of DNA unwinding during eukaryotic DNA replication.''; PubMed Europe PMC Scholia
  34. Maga G, Stucki M, Spadari S, Hübscher U.; ''DNA polymerase switching: I. Replication factor C displaces DNA polymerase alpha prior to PCNA loading.''; PubMed Europe PMC Scholia
  35. Lee SH, Hurwitz J.; ''Mechanism of elongation of primed DNA by DNA polymerase delta, proliferating cell nuclear antigen, and activator 1.''; PubMed Europe PMC Scholia
  36. Liu L, Mo J, Rodriguez-Belmonte EM, Lee MY.; ''Identification of a fourth subunit of mammalian DNA polymerase delta.''; PubMed Europe PMC Scholia
  37. Bae SH, Bae KH, Kim JA, Seo YS.; ''RPA governs endonuclease switching during processing of Okazaki fragments in eukaryotes.''; PubMed Europe PMC Scholia
  38. 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 Scholia
  39. 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 Scholia
  40. Schaarschmidt D, Ladenburger EM, Keller C, Knippers R.; ''Human Mcm proteins at a replication origin during the G1 to S phase transition.''; PubMed Europe PMC Scholia


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113478view11:55, 2 November 2020ReactomeTeamReactome version 74
112678view16:07, 9 October 2020ReactomeTeamReactome version 73
101595view11:46, 1 November 2018ReactomeTeamreactome version 66
101131view21:31, 31 October 2018ReactomeTeamreactome version 65
100659view20:05, 31 October 2018ReactomeTeamreactome version 64
100209view16:50, 31 October 2018ReactomeTeamreactome version 63
99760view15:16, 31 October 2018ReactomeTeamreactome version 62 (2nd attempt)
99320view12:47, 31 October 2018ReactomeTeamreactome version 62
93769view13:35, 16 August 2017ReactomeTeamreactome version 61
93293view11:19, 9 August 2017ReactomeTeamreactome version 61
86379view09:16, 11 July 2016ReactomeTeamreactome version 56
83144view10:09, 18 November 2015ReactomeTeamVersion54
76968view08:25, 17 July 2014ReactomeTeamFixed remaining interactions
76673view12:04, 16 July 2014ReactomeTeamFixed remaining interactions
76002view10:06, 11 June 2014ReactomeTeamRe-fixing comment source
75705view11:04, 10 June 2014ReactomeTeamReactome 48 Update
75061view13:57, 8 May 2014AnweshaFixing comment source for displaying WikiPathways description
74705view08:46, 30 April 2014ReactomeTeamReactome46
45107view22:33, 6 October 2011KhanspersOntology Term : 'DNA replication pathway' added !
45106view22:32, 6 October 2011KhanspersOntology Term : 'S phase pathway' added !
42140view22:00, 4 March 2011MaintBotAutomatic update
39951view05:58, 21 January 2011MaintBotNew pathway

External references


View all...
NameTypeDatabase referenceComment
26S proteasomeComplexR-HSA-68819 (Reactome)
ADPMetaboliteCHEBI:456216 (ChEBI)
AMPMetaboliteCHEBI:16027 (ChEBI)
ANAPC1 ProteinQ9H1A4 (Uniprot-TrEMBL)
ANAPC10 ProteinQ9UM13 (Uniprot-TrEMBL)
ANAPC11 ProteinQ9NYG5 (Uniprot-TrEMBL)
ANAPC15 ProteinP60006 (Uniprot-TrEMBL)
ANAPC16 ProteinQ96DE5 (Uniprot-TrEMBL)
ANAPC2 ProteinQ9UJX6 (Uniprot-TrEMBL)
ANAPC4 ProteinQ9UJX5 (Uniprot-TrEMBL)
ANAPC5 ProteinQ9UJX4 (Uniprot-TrEMBL)
ANAPC7 ProteinQ9UJX3 (Uniprot-TrEMBL)
ATP MetaboliteCHEBI:30616 (ChEBI)
ATPMetaboliteCHEBI:30616 (ChEBI)
CCNA1 ProteinP78396 (Uniprot-TrEMBL)
CCNA2 ProteinP20248 (Uniprot-TrEMBL)
CCNA:p-T160-CDK2,CCNE:p-T160-CDK2ComplexR-HSA-8848491 (Reactome)
CCNA:p-T160-CDK2ComplexR-HSA-187952 (Reactome)
CCNE1 ProteinP24864 (Uniprot-TrEMBL)
CCNE2 ProteinO96020 (Uniprot-TrEMBL)
CDC16 ProteinQ13042 (Uniprot-TrEMBL)
CDC23 ProteinQ9UJX2 (Uniprot-TrEMBL)
CDC26 ProteinQ8NHZ8 (Uniprot-TrEMBL)
CDC27 ProteinP30260 (Uniprot-TrEMBL)
CDC45 ProteinO75419 (Uniprot-TrEMBL)
CDC45ProteinO75419 (Uniprot-TrEMBL)
CDC6 ProteinQ99741 (Uniprot-TrEMBL)
CDC6ProteinQ99741 (Uniprot-TrEMBL)
CDT1 ProteinQ9H211 (Uniprot-TrEMBL)
CMPMetaboliteCHEBI:17361 (ChEBI)
CTP MetaboliteCHEBI:17677 (ChEBI)
CUL1 ProteinQ13616 (Uniprot-TrEMBL)
DNA Polymerase delta tetramerComplexR-HSA-68450 (Reactome)
DNA polymerase

alpha:primase:DNA polymerase alpha:origin

ComplexR-HSA-68510 (Reactome)
DNA polymerase alpha:primaseComplexR-HSA-68507 (Reactome)
DNA polymerase epsilonComplexR-HSA-68483 (Reactome)
DNA primer R-ALL-68424 (Reactome)
DNA2 ProteinP51530 (Uniprot-TrEMBL)
DNA2ProteinP51530 (Uniprot-TrEMBL)
FEN1ProteinP39748 (Uniprot-TrEMBL)
FZR1 ProteinQ9UM11 (Uniprot-TrEMBL)
Flap R-ALL-68454 (Reactome)
GINS complexComplexR-HSA-176952 (Reactome)
GINS1 ProteinQ14691 (Uniprot-TrEMBL)
GINS1ProteinQ14691 (Uniprot-TrEMBL)
GINS2 ProteinQ9Y248 (Uniprot-TrEMBL)
GINS2ProteinQ9Y248 (Uniprot-TrEMBL)
GINS3 ProteinQ9BRX5 (Uniprot-TrEMBL)
GINS3ProteinQ9BRX5 (Uniprot-TrEMBL)
GINS4 ProteinQ9BRT9 (Uniprot-TrEMBL)
GINS4ProteinQ9BRT9 (Uniprot-TrEMBL)
GMPMetaboliteCHEBI:17345 (ChEBI)
GTP MetaboliteCHEBI:15996 (ChEBI)
LIG1ProteinP18858 (Uniprot-TrEMBL)
MCM2 ProteinP49736 (Uniprot-TrEMBL)
MCM2-7ComplexR-HSA-68558 (Reactome)
MCM2ProteinP49736 (Uniprot-TrEMBL)
MCM3 ProteinP25205 (Uniprot-TrEMBL)
MCM3ProteinP25205 (Uniprot-TrEMBL)
MCM4 ProteinP33991 (Uniprot-TrEMBL)
MCM5 ProteinP33992 (Uniprot-TrEMBL)
MCM5ProteinP33992 (Uniprot-TrEMBL)
MCM6 ProteinQ14566 (Uniprot-TrEMBL)
MCM7 ProteinP33993 (Uniprot-TrEMBL)
MCM8 ProteinQ9UJA3 (Uniprot-TrEMBL)
MCM8ProteinQ9UJA3 (Uniprot-TrEMBL)
Mcm4,6,7 complexComplexR-HSA-69018 (Reactome)
NTPComplexR-ALL-30595 (Reactome)
ORC1 ProteinQ13415 (Uniprot-TrEMBL)
ORC2 ProteinQ13416 (Uniprot-TrEMBL)
ORC3 ProteinQ9UBD5 (Uniprot-TrEMBL)
ORC4 ProteinO43929 (Uniprot-TrEMBL)
ORC5 ProteinO43913 (Uniprot-TrEMBL)
ORC6 ProteinQ9Y5N6 (Uniprot-TrEMBL)
Okazaki fragment R-ALL-68452 (Reactome)
Okazaki fragment minus Flap R-ALL-68469 (Reactome)
Okazaki fragmentR-ALL-68452 (Reactome)
PCNA ProteinP12004 (Uniprot-TrEMBL)
PCNA homotrimerComplexR-HSA-68440 (Reactome)
POLA1 ProteinP09884 (Uniprot-TrEMBL)
POLA2 ProteinQ14181 (Uniprot-TrEMBL)
POLD1 ProteinP28340 (Uniprot-TrEMBL)
POLD2 ProteinP49005 (Uniprot-TrEMBL)
POLD3 ProteinQ15054 (Uniprot-TrEMBL)
POLD4 ProteinQ9HCU8 (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)
PolyUb,p-S,T-ORC1ProteinQ13415 (Uniprot-TrEMBL)


fragment complex
ComplexR-HSA-68453 (Reactome)

complex:Okazaki fragment:Flap:RPA

ComplexR-HSA-68466 (Reactome)

complex:Okazaki fragment:Flap:RPA

ComplexR-HSA-68463 (Reactome)


ComplexR-HSA-68455 (Reactome)

complex:Okazaki fragments:Remaining

ComplexR-HSA-68468 (Reactome)

complex:nicked DNA from adjacent

Okazaki fragments
ComplexR-HSA-68470 (Reactome)
Processive complexComplexR-HSA-68451 (Reactome)
RBX1 ProteinP62877 (Uniprot-TrEMBL)

Heteropentamer:RNA primer-DNA primer:origin duplex:PCNA

ComplexR-HSA-68471 (Reactome)

Heteropentamer:RNA primer-DNA primer:origin

ComplexR-HSA-68437 (Reactome)
RFC HeteropentamerComplexR-HSA-68436 (Reactome)
RFC1 ProteinP35251 (Uniprot-TrEMBL)
RFC2 ProteinP35250 (Uniprot-TrEMBL)
RFC3 ProteinP40938 (Uniprot-TrEMBL)
RFC4 ProteinP35249 (Uniprot-TrEMBL)
RFC5 ProteinP40937 (Uniprot-TrEMBL)
RNA primer R-ALL-68422 (Reactome)
RNA primer-DNA


ComplexR-HSA-68441 (Reactome)
RNA primer-DNA


ComplexR-HSA-68425 (Reactome)
RNA primer:origin

duplex:DNA polymerase alpha:primase

ComplexR-HSA-68423 (Reactome)
RPA heterotrimerComplexR-HSA-68462 (Reactome)
RPA1 ProteinP27694 (Uniprot-TrEMBL)
RPA2 ProteinP15927 (Uniprot-TrEMBL)
RPA3 ProteinP35244 (Uniprot-TrEMBL)
RPS27A(1-76) ProteinP62979 (Uniprot-TrEMBL)
Remaining Flap R-ALL-68467 (Reactome)
Replication Fork R-ALL-169515 (Reactome)
Replication ForkR-ALL-169515 (Reactome)
SCF(SKP2) complexComplexR-HSA-8939693 (Reactome)
SHFM1 ProteinP60896 (Uniprot-TrEMBL)
SKP1 ProteinP63208 (Uniprot-TrEMBL)
SKP2 ProteinQ13309 (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)
UBE2C ProteinO00762 (Uniprot-TrEMBL)
UBE2D1 ProteinP51668 (Uniprot-TrEMBL)
UBE2E1 ProteinP51965 (Uniprot-TrEMBL)
UBE2S ProteinQ16763 (Uniprot-TrEMBL)
UMPMetaboliteCHEBI:16695 (ChEBI)
UTP MetaboliteCHEBI:15713 (ChEBI)
UbComplexR-HSA-113595 (Reactome)
UbComplexR-HSA-68524 (Reactome)
Unwinding complex at replication forkComplexR-HSA-176949 (Reactome)
Unwound forkR-ALL-169509 (Reactome)
dATPMetaboliteCHEBI:16284 (ChEBI)
dCTPMetaboliteCHEBI:16311 (ChEBI)
dGTPMetaboliteCHEBI:16497 (ChEBI)
dTTPMetaboliteCHEBI:18077 (ChEBI)
ligated okazaki fragmentR-ALL-69172 (Reactome)
origin of replication R-ALL-68419 (Reactome)
p-CDC6ProteinQ99741 (Uniprot-TrEMBL)
p-S,T-ORC1ProteinQ13415 (Uniprot-TrEMBL)
p-T160-CDK2 ProteinP24941 (Uniprot-TrEMBL)
phospho-APC/C:Cdh1 complexComplexR-HSA-174181 (Reactome)


ComplexR-HSA-157563 (Reactome)
pre-replicative complexComplexR-HSA-68559 (Reactome)
ubiquitinated Cdc6ComplexR-HSA-68570 (Reactome)

Annotated Interactions

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SourceTargetTypeDatabase referenceComment
26S proteasomemim-catalysisR-HSA-68948 (Reactome)
26S proteasomemim-catalysisR-HSA-69016 (Reactome)
ADPArrowR-HSA-68944 (Reactome)
ADPArrowR-HSA-69005 (Reactome)
ADPArrowR-HSA-69063 (Reactome)
AMPArrowR-HSA-69144 (Reactome)
ATPR-HSA-68944 (Reactome)
ATPR-HSA-69005 (Reactome)
ATPR-HSA-69015 (Reactome)
ATPR-HSA-69063 (Reactome)
CCNA:p-T160-CDK2,CCNE:p-T160-CDK2mim-catalysisR-HSA-69005 (Reactome)
CCNA:p-T160-CDK2mim-catalysisR-HSA-68944 (Reactome)
CDC45R-HSA-176942 (Reactome)
CDC6R-HSA-69005 (Reactome)
CMPArrowR-HSA-69144 (Reactome)
DNA Polymerase delta tetramerR-HSA-69074 (Reactome)
DNA Polymerase delta tetramermim-catalysisR-HSA-69116 (Reactome)
DNA polymerase

alpha:primase:DNA polymerase alpha:origin

R-HSA-68913 (Reactome)
DNA polymerase

alpha:primase:DNA polymerase alpha:origin

mim-catalysisR-HSA-68913 (Reactome)
DNA polymerase alpha:primasemim-catalysisR-HSA-68950 (Reactome)
DNA polymerase epsilonArrowR-HSA-68913 (Reactome)
DNA2ArrowR-HSA-69144 (Reactome)
DNA2R-HSA-69142 (Reactome)
FEN1mim-catalysisR-HSA-69152 (Reactome)
GINS complexArrowR-HSA-176956 (Reactome)
GINS complexR-HSA-176942 (Reactome)
GINS1R-HSA-176956 (Reactome)
GINS2R-HSA-176956 (Reactome)
GINS3R-HSA-176956 (Reactome)
GINS4R-HSA-176956 (Reactome)
GMPArrowR-HSA-69144 (Reactome)
LIG1mim-catalysisR-HSA-69173 (Reactome)
MCM2-7R-HSA-176942 (Reactome)
MCM2-7R-HSA-69019 (Reactome)
MCM2-7mim-catalysisR-HSA-169468 (Reactome)
MCM2ArrowR-HSA-69019 (Reactome)
MCM3ArrowR-HSA-69019 (Reactome)
MCM5ArrowR-HSA-69019 (Reactome)
MCM8mim-catalysisR-HSA-169461 (Reactome)
Mcm4,6,7 complexArrowR-HSA-69019 (Reactome)
NTPR-HSA-68913 (Reactome)
Okazaki fragmentR-HSA-69173 (Reactome)
PCNA homotrimerR-HSA-69063 (Reactome)
PolyUb,p-S,T-ORC1ArrowR-HSA-68946 (Reactome)
PolyUb,p-S,T-ORC1ArrowR-HSA-68947 (Reactome)
PolyUb,p-S,T-ORC1R-HSA-68947 (Reactome)
PolyUb,p-S,T-ORC1R-HSA-68948 (Reactome)


fragment complex
ArrowR-HSA-69116 (Reactome)


fragment complex
R-HSA-69127 (Reactome)

complex:Okazaki fragment:Flap:RPA

ArrowR-HSA-69142 (Reactome)

complex:Okazaki fragment:Flap:RPA

R-HSA-69144 (Reactome)

complex:Okazaki fragment:Flap:RPA

ArrowR-HSA-69140 (Reactome)

complex:Okazaki fragment:Flap:RPA

R-HSA-69142 (Reactome)


ArrowR-HSA-69127 (Reactome)


R-HSA-69140 (Reactome)

complex:Okazaki fragments:Remaining

ArrowR-HSA-69144 (Reactome)

complex:Okazaki fragments:Remaining

R-HSA-69152 (Reactome)

complex:nicked DNA from adjacent

Okazaki fragments
ArrowR-HSA-69152 (Reactome)
Processive complexArrowR-HSA-69074 (Reactome)
Processive complexR-HSA-69116 (Reactome)
R-HSA-169461 (Reactome) The MCM2-7 related protein, MCM8, is required to replicate chromosomal DNA in Xenopus egg extracts. MCM8 binds chromatin upon initiation of DNA synthesis. It may function as an helicase in the elongation step.
R-HSA-169468 (Reactome) In budding yeast, all MCM proteins have been proved to be essential for elongation. The active form of this protein complex may be a heterohexamer. A subcomplex of MCM proteins consisting fo MCM4,6, and -7 has a weak helicase activity that may contribute to DNA unwinding.
R-HSA-176942 (Reactome) By applying the chromatin immunoprecipitation technique to paused forks, certain proteins like DNA pol alpha, DNA pol delta, DNA pol epsilon, MCM2-7, CDC45, GINS and MCM10 were identified. By uncoupling a helicase at the site using a polymerase inhibitor, MCM2-7, GINS complex and CDC45 alone were found to be enriched at the paused fork suggesting these proteins may form a part of an "unwindosome" at the replicating fork.
R-HSA-176956 (Reactome) At the beginning of this reaction, 1 molecule of 'PSF3p', 1 molecule of 'SLD5P', 1 molecule of 'PSF2p', and 1 molecule of 'PSF1p' are present. At the end of this reaction, 1 molecule of 'GINS complex' is present.

This reaction takes place in the 'nucleus'.

R-HSA-68913 (Reactome) At the beginning of this reaction, 1 molecule of 'DNA polymerase alpha:primase:DNA polymerase alpha:origin complex', and 1 molecule of 'NTP' are present. At the end of this reaction, 1 molecule of 'DNA polymerase epsilon', and 1 molecule of 'RNA primer:origin duplex:DNA polymerase alpha:primase complex' are present.

This reaction takes place in the 'nucleus' and is mediated by the 'DNA-directed RNA polymerase activity' of 'DNA polymerase alpha:primase'.

R-HSA-68944 (Reactome) At the beginning of this reaction, 1 molecule of 'ATP', and 1 molecule of 'pre-replicative complex' are present. At the end of this reaction, 1 molecule of 'phosphorylated Orc1', 1 molecule of 'pre-replicative complex (Orc1-minus)', and 1 molecule of 'ADP' are present.

This reaction takes place in the 'nucleus' and is mediated by the 'kinase activity' of 'Cyclin A:Cdk2 complex'.

R-HSA-68946 (Reactome) ORC1 is ubiquitinated by the SKP2-containing ubiquitin ligase complex and targeted for proteasome-mediated degradation, which may play an important role in the maintenace of ploidy. While the ORC1 region phosphorylated by the CCNA:CDK1 complex is involved in the interaction with SKP2, phosphorylation may not be a pre-requisite for ORC1 ubiquitination (Mendez et al. 2002).
R-HSA-68947 (Reactome) Ubiquitinated ORC1 translocates to the cytosol (Li and DePamphilis 2002).
R-HSA-68948 (Reactome) Ubiquitinated ORC1 is degraded by the proteasome in the cytosol (Li and DePamphilis 2002, Mendez et al. 2002).
R-HSA-68950 (Reactome) At the beginning of this reaction, 1 molecule of 'dTTP', 1 molecule of 'dGTP', 1 molecule of 'dATP', 1 molecule of 'RNA primer:origin duplex:DNA polymerase alpha:prim