Synthesis of DNA (Homo sapiens)

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2157, 9, 1326, 33101512122812, 21, 23361236618, 321424, 364, 5, 13, 16, 27...24352, 13, 17, 20, 38...2529, 37cytosolnucleoplasmPSME2 CCNA:p-T160-CDK2,CCNE:p-T160-CDK2RPA3 PRIM2 PSMF1 CCNA2 ANAPC15 PSME4 MCM3 ORC6 DNA primer Okazaki fragment POLD4 MCM7 PSMD2 POLE ADPUBC(457-532) UBB(1-76) RFC4 GINS2CCNA2 RFC5 Processivecomplex:Okazakifragment:Flap:RPAheterotrimer:dna2POLE2 UBE2E1 PSMD7 ADPANAPC10 p-S,T-ORC1UBC(153-228) phospho-APC/C:Cdh1complexUBC(381-456) UBC(533-608) FZR1 POLE Unwound forkdATPUBA52(1-76) UBA52(1-76) ANAPC4 CDC6 PRIM1 PSMB11 ANAPC2 POLD3 UBC(457-532) PSMB9 UBC(609-684) UBC(153-228) origin of replication RPA2 PRIM2 PSMB10 ATP UBB(1-76) RPA heterotrimerp-CDC6DNA primer Processive complexFEN1CDC45GINS1 POLA2 PCNA homotrimerMCM8ORC4 POLA2 RNA primer UBC(533-608) RNA primer:originduplex:DNApolymerasealpha:primasecomplexorigin of replication MCM7 POLE4 adenosine5'-monophosphateGINS2 POLE2 Processivecomplex:Okazakifragment complexUBE2D1 RPA1 Okazaki fragment minus Flap UBC(609-684) PRIM2 ATPPOLD4 POLD1 PSMC5 POLA2 POLD4 UBC(77-152) Okazaki fragment RFC HeteropentamerProcessivecomplex:Okazakifragments:RemainingFlapRFC3 CDC27 UBC(305-380) MCM4 p-CDC6DNA primer POLD4 PRIM2 UBC(609-684) MCM3 PCNA DNA primer PSMB2 ORC4 MCM5RFC2 PolyUb,p-S,T-ORC1GINS complexDNA polymerasealpha:primase:DNApolymerasealpha:origincomplexorigin of replication origin of replication PRIM2 MCM2 DNA2PSMA4 RFC3 ORC5 RPA2 PSMD6 PSMA5 Processivecomplex:Okazakifragment:FlapFlap UBB(1-76) RNA primer UBC(229-304) CDC6POLA1 GINS1PRIM1 CDT1 RFCHeteropentamer:RNAprimer-DNAprimer:originduplexProcessivecomplex:Okazakifragment:Flap:RPAheterotrimerorigin of replication CDC23 UBC(1-76) RNA primer MCM2ORC5 RNA primer PSMB7 Okazaki fragment PRIM1 RNA primer-DNAprimer:originduplex:PCNAPSMC1 Flap PRIM2 POLD2 MCM8 MCM4 PSMB8 ORC6 Okazaki fragmentPSMA6 POLD1 uridine5'-monophosphateRemaining Flap RNA primer POLD4 guanosine5'-monophosphateSHFM1 ANAPC11 pre-replicativecomplexPRIM2 DNA primer POLD3 PSMD8 RFC4 MCM6 RPA1 UBC(381-456) GINS4 PSMB5 PSMD3 PCNA RPS27A(1-76) MCM7 PSMD5 PRIM2 RFCHeteropentamer:RNAprimer-DNAprimer:originduplex:PCNAhomotrimerPOLA2 UBB(153-228) POLD2 PRIM2 UBB(77-152) DNA Polymerase deltatetramerMCM3 GINS4POLA2 PCNA ORC2 POLE3 MCM5 origin of replication Replication ForkPSMA1 POLD1 MCM7 UBB(77-152) RPS27A(1-76) pre-replicativecomplex(Orc1-minus)RFC5 POLA1 PSMB6 PRIM1 Okazaki fragment RFC2 PSMA7 ADPPOLD2 MCM6 Ubligated okazakifragmentCCNE2 DNA primer POLD3 SCF(SKP2) complexPOLA1 MCM8 PRIM1 ORC1 PRIM2 ATPPOLD1 Replication Fork dCTPPCNA PSMC4 MCM3 ATPPSMA8 MCM7 UBC(153-228) PRIM1 PCNA POLA1 PolyUb,p-S,T-ORC1POLA2 origin of replication DNA polymerasealpha:primasePRIM1 PSMB3 UTP ORC2 POLD2 POLD2 CDC26 UBC(305-380) UBC(229-304) ATPMCM2 POLD1 PSMD1 UBC(229-304) ORC3 POLA1 PSMA2 MCM5 RPS27A(1-76) PRIM2 RPA1 PSMD12 RNA primer ANAPC5 POLA2 RNA primer UBB(77-152) RFC1 UBC(1-76) POLA2 PSMB4 origin of replication MCM5 RNA primer POLA1 Unwinding complex atreplication forkPOLA2 MCM2-7POLA1 PRIM1 CTP POLE4 RFC1 PCNA PSME1 MCM5 UBC(381-456) MCM2 PSMD10 RFC3 MCM6 GINS1 PSMC2 POLA1 Okazaki fragment GINS3ANAPC16 dGTPUBA52(1-76) Processivecomplex:nicked DNAfrom adjacentOkazaki fragmentsMCM6 PCNA RNA primer PRIM2 RNA primer cytidine5'-monophosphateCDC6 POLA1 UBC(77-152) LIG1UBC(77-152) origin of replication p-T160-CDK2 RFC4 origin of replication ubiquitinated Cdc6CDT1 MCM4 POLA2 origin of replication DNA polymeraseepsilonDNA primer dTTPMCM6 RNA primer origin of replication PRIM1 POLA2 PSMD13 PSMA3 CCNA1 POLD4 PSMD9 DNA2 UBC(1-76) CDC45 POLD1 MCM4 PSMD14 26S proteasomePSMB1 POLD4 POLA2 GINS2 UbCCNA1 SKP1 POLA2 UBE2C POLD2 UBB(153-228) RFC2 UBB(153-228) RBX1 PRIM2 MCM2 POLD2 DNA primer CDC16 PCNA RFC5 POLD2 RFC1 POLD3 DNA primer SKP2 POLD3 ANAPC7 RNA primer-DNAprimer:originduplexRNA primer POLA2 GINS3 DNA primer UBC(305-380) PSMC6 p-T160-CDK2 POLA1 PSMD4 GINS3 RPA2 POLD4 CUL1 PRIM1 PSME3 PCNA POLA1 PRIM1 PRIM1 POLA1 CDC6 GINS4 origin of replication POLD1 POLD3 Mcm4,6,7 complexPOLD1 POLD3 origin of replication CCNE1 origin of replication CCNA:p-T160-CDK2RPA3 PSMD11 ANAPC1 UBC(457-532) GTP PSMC3 PRIM1 PRIM1 PCNA RPA3 Flap UBC(533-608) NTPPRIM2 POLD3 POLA1 POLA1 MCM3DNA primer ORC3 POLE3 MCM4 1, 819341022330, 3411


Description

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.

Comments

Reactome-Converter 
Pathway is converted from Reactome ID: 69239
Reactome-version 
Reactome version: 66

Quality Tags

Ontology Terms

 

Bibliography

View all...
  1. Li Y, Pursell ZF, Linn S.; ''Identification and cloning of two histone fold motif-containing subunits of HeLa DNA polymerase epsilon.''; PubMed
  2. Bambara RA, Murante RS, Henricksen LA.; ''Enzymes and reactions at the eukaryotic DNA replication fork.''; PubMed
  3. 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
  4. 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
  5. Hindges R, Hübscher U.; ''DNA polymerase delta, an essential enzyme for DNA transactions.''; PubMed
  6. 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
  7. Maga G, Stucki M, Spadari S, Hübscher U.; ''DNA polymerase switching: I. Replication factor C displaces DNA polymerase alpha prior to PCNA loading.''; PubMed
  8. 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
  9. 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
  10. 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
  11. 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
  12. Bae SH, Bae KH, Kim JA, Seo YS.; ''RPA governs endonuclease switching during processing of Okazaki fragments in eukaryotes.''; PubMed
  13. 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
  14. 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
  15. Jiang W, Wells NJ, Hunter T.; ''Multistep regulation of DNA replication by Cdk phosphorylation of HsCdc6.''; PubMed
  16. Lee MY, Tan CK, So AG, Downey KM.; ''Purification of deoxyribonucleic acid polymerase delta from calf thymus: partial characterization of physical properties.''; PubMed
  17. Nethanel T, Zlotkin T, Kaufmann G.; ''Assembly of simian virus 40 Okazaki pieces from DNA primers is reversibly arrested by ATP depletion.''; PubMed
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  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
  22. Plafker SM, Plafker KS, Weissman AM, Macara IG.; ''Ubiquitin charging of human class III ubiquitin-conjugating enzymes triggers their nuclear import.''; PubMed
  23. 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
  24. 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
  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
  26. Harrington JJ, Lieber MR.; ''DNA structural elements required for FEN-1 binding.''; PubMed
  27. Liu L, Mo J, Rodriguez-Belmonte EM, Lee MY.; ''Identification of a fourth subunit of mammalian DNA polymerase delta.''; PubMed
  28. Chang LM, Rafter E, Augl C, Bollum FJ.; ''Purification of a DNA polymerase-DNA primase complex from calf thymus glands.''; PubMed
  29. Schaarschmidt D, Ladenburger EM, Keller C, Knippers R.; ''Human Mcm proteins at a replication origin during the G1 to S phase transition.''; PubMed
  30. Voges D, Zwickl P, Baumeister W.; ''The 26S proteasome: a molecular machine designed for controlled proteolysis.''; PubMed
  31. 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
  32. Mossi R, Hübscher U.; ''Clamping down on clamps and clamp loaders--the eukaryotic replication factor C.''; PubMed
  33. Harrington JJ, Lieber MR.; ''The characterization of a mammalian DNA structure-specific endonuclease.''; PubMed
  34. 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
  35. 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
  36. 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
  37. 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
  38. Lee SH, Hurwitz J.; ''Mechanism of elongation of primed DNA by DNA polymerase delta, proliferating cell nuclear antigen, and activator 1.''; PubMed
  39. Brown WC, Campbell JL.; ''Interaction of proliferating cell nuclear antigen with yeast DNA polymerase delta.''; PubMed

History

View all...
CompareRevisionActionTimeUserComment
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

DataNodes

View all...
NameTypeDatabase referenceComment
26S proteasomeComplexR-HSA-68819 (Reactome)
ADPMetaboliteCHEBI:16761 (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:15422 (ChEBI)
ATPMetaboliteCHEBI:15422 (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)
CTP MetaboliteCHEBI:17677 (ChEBI)
CUL1 ProteinQ13616 (Uniprot-TrEMBL)
DNA Polymerase delta tetramerComplexR-HSA-68450 (Reactome)
DNA polymerase

alpha:primase:DNA polymerase alpha:origin

complex
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)
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)
Processive

complex:Okazaki

fragment complex
ComplexR-HSA-68453 (Reactome)
Processive

complex:Okazaki fragment:Flap:RPA

heterotrimer:dna2
ComplexR-HSA-68466 (Reactome)
Processive

complex:Okazaki fragment:Flap:RPA

heterotrimer
ComplexR-HSA-68463 (Reactome)
Processive

complex:Okazaki

fragment:Flap
ComplexR-HSA-68455 (Reactome)
Processive

complex:Okazaki fragments:Remaining

Flap
ComplexR-HSA-68468 (Reactome)
Processive

complex:nicked DNA from adjacent

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

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

homotrimer
ComplexR-HSA-68471 (Reactome)
RFC

Heteropentamer:RNA primer-DNA primer:origin

duplex
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

primer:origin

duplex:PCNA
ComplexR-HSA-68441 (Reactome)
RNA primer-DNA

primer:origin

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

duplex:DNA polymerase alpha:primase

complex
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)
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)
adenosine 5'-monophosphateMetaboliteCHEBI:16027 (ChEBI)
cytidine 5'-monophosphateMetaboliteCHEBI:17361 (ChEBI)
dATPMetaboliteCHEBI:16284 (ChEBI)
dCTPMetaboliteCHEBI:16311 (ChEBI)
dGTPMetaboliteCHEBI:16497 (ChEBI)
dTTPMetaboliteCHEBI:18077 (ChEBI)
guanosine 5'-monophosphateMetaboliteCHEBI:17345 (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)
pre-replicative

complex

(Orc1-minus)
ComplexR-HSA-157563 (Reactome)
pre-replicative complexComplexR-HSA-68559 (Reactome)
ubiquitinated Cdc6ComplexR-HSA-68570 (Reactome)
uridine 5'-monophosphateMetaboliteCHEBI:16695 (ChEBI)

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)
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)
DNA Polymerase delta tetramerR-HSA-69074 (Reactome)
DNA Polymerase delta tetramermim-catalysisR-HSA-69116 (Reactome)
DNA polymerase

alpha:primase:DNA polymerase alpha:origin

complex
R-HSA-68913 (Reactome)
DNA polymerase

alpha:primase:DNA polymerase alpha:origin

complex
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)
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)
Processive

complex:Okazaki

fragment complex
ArrowR-HSA-69116 (Reactome)
Processive

complex:Okazaki

fragment complex
R-HSA-69127 (Reactome)
Processive

complex:Okazaki fragment:Flap:RPA

heterotrimer:dna2
ArrowR-HSA-69142 (Reactome)
Processive

complex:Okazaki fragment:Flap:RPA

heterotrimer:dna2
R-HSA-69144 (Reactome)
Processive

complex:Okazaki fragment:Flap:RPA

heterotrimer
ArrowR-HSA-69140 (Reactome)
Processive

complex:Okazaki fragment:Flap:RPA

heterotrimer
R-HSA-69142 (Reactome)
Processive

complex:Okazaki

fragment:Flap
ArrowR-HSA-69127 (Reactome)
Processive

complex:Okazaki

fragment:Flap
R-HSA-69140 (Reactome)
Processive

complex:Okazaki fragments:Remaining

Flap
ArrowR-HSA-69144 (Reactome)
Processive

complex:Okazaki fragments:Remaining

Flap
R-HSA-69152 (Reactome)
Processive

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:primase complex', and 1 molecule of 'dCTP' are present. At the end of this reaction, 1 molecule of 'RNA primer-DNA primer:origin duplex' is present.

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

R-HSA-69005 (Reactome) At the beginning of this reaction, 1 molecule of 'CDC6', and 1 molecule of 'ATP' are present. At the end of this reaction, 1 molecule of 'ADP', and 1 molecule of 'phosphorylated Cdc6' are present.

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

R-HSA-69006 (Reactome) In this reaction, 1 molecule of 'phosphorylated Cdc6' is translocated from nucleoplasm to cytosol.

This movement of the molecule occurs through the 'nuclear pore'.

R-HSA-69015 (Reactome) At the beginning of this reaction, 1 molecule of 'phosphorylated Cdc6', 1 molecule of 'ubiquitin', and 1 molecule of 'ATP' are present. At the end of this reaction, 1 molecule of 'ubiquitinated Cdc6' is present.

This reaction takes place in the 'cytosol' and is mediated by the 'endopeptidase activity' of 'anaphase-promoting complex (APC)'.

R-HSA-69016 (Reactome) At the beginning of this reaction, 1 molecule of 'ubiquitinated Cdc6' 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-69019 (Reactome) At the start of the elongation phase of DNA replication, the Mcm2-7 complex may re-arrange to function as the replicative helicase associated with the replication fork. In general, a replicative helicase is associated with the replication fork and unwinds DNA ahead of the polymerase. In yeast, the Mcm proteins associate with origin DNA in G1 phase and then exit the origin upon replication initiation, consistent with moving out of the origin with the replication fork. The Mcm2-7 complex is a ring-shaped hexamer. Complexes of Mcm4, Mcm6 and Mcm7 proteins from humans or S. pombe display a modest ATP-dependent helicase activity in vitro. Consistent with the hypothesis that eukaryotic Mcm complexes function as helicases, an archaeal Mcm homolog is a ring-shaped double hexamer that has a processive DNA unwinding activity. Mcm proteins may have additional functions during elongation, as uninterrupted function of all six is required for replication fork progression in budding yeast. Mcm4,6,7 helicase activity may be negatively regulated in two ways. Mcm2, Mcm4, Mcm6, and Mcm7 also form a stable complex which, however, has no helicase activity, suggesting that Mcm2 inhibits DNA unwinding by Mcm4,6,7. In addition, phosphorylation of human Mcm4,6,7 complex by CDK inhibits its helicase activity.
R-HSA-69053 (Reactome) Once the RNA-DNA primer is synthesized, replication factor C (RFC) initiates a reaction called "polymerase switching"; pol delta, the processive enzyme replaces pol alpha, the priming enzyme. RFC binds to the 3'-end of the RNA-DNA primer on the Primosome, to displace the pol alpha primase complex. The binding of RFC triggers the binding of the primer recognition complex.
R-HSA-69063 (Reactome) The binding of the primer recognition complex involves the loading of proliferating cell nuclear antigen (PCNA). Replication Factor C transiently opens the PCNA toroid in an ATP-dependent reaction, and then allows PCNA to re-close around the double helix adjacent to the primer terminus. This leads to the formation of the "sliding clamp".
R-HSA-69068 (Reactome) Replication factor C is proposed to dissociate from PCNA following sliding clamp formation, and the DNA toroid alone tethers pol delta to the DNA.