Synthesis of DNA (Homo sapiens)

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331526266, 7, 203323, 29, 3333113638242610, 352, 181, 3124215, 7, 16, 19, 22...2643, 5, 7, 14, 19...17cytosolnucleoplasmUBA52(1-76) MCM3 PSMC3 GINS4 PCNA PSMD7 POLA1 dTTPRPA3 FEN1POLE DNA primer UBB(153-228) PSMD2 UBC(381-456) DNA Polymerase deltatetramerUBA52(1-76) RFCHeteropentamer:RNAprimer-DNAprimer:originduplexanaphase-promotingcomplex (APC)PRIM2 DNA2UBC(77-152) POLA1 RNA primer Replication ForkPSMD6 26S proteasomeDNA primer CCNA1 CyclinA:Cdk2:substratecomplexRNA primer RPA heterotrimerRPS27A(1-76) RNA primer UBC(229-304) PSMA4 RFC1 ORC5 GINS2 UBC(153-228) POLE3 UBC(305-380) Okazaki fragment Processivecomplex:Okazakifragment complexGINS4MCM4 POLD3 UBC(153-228) UBC(1-76) PRIM2 RFC5 PSMB11 PSMA1 origin of replication DNA primer RPA1 Okazaki fragment RFC2 UBC(457-532) MCM7 p-S,T-ORC1PRIM1 CDKN1B PRIM1 pre-replicativecomplex(Orc1-minus)POLE2 PCNA PCNA origin of replication ubiquitinated Orc1RPS27A(1-76) UBC(609-684) CTP RNA primer UBC(609-684) RPA2 RPA3 Processivecomplex:Okazakifragment:FlapPOLA1 RFC1 RFC3 DNA polymerasealpha:primaseUBC(533-608) ATPPOLD4 CDC45 MCM2 POLD1 RPA2 ORC1 PRIM1 PSMD4 MCM3dATPRFC5 POLD3 UBB(77-152) RNA primer RNA primer UBB(77-152) ADPRNA primer POLD4 PRIM1 MCM6 UBB(1-76) PRIM2 CDC45MCM3 POLD4 PSMD8 RNA primer UBB(77-152) PRIM1 GMPUBB(153-228) POLA2 DNA primer MCM8UBC(229-304) MCM8 PSMA6 UBC(153-228) POLD3 UBC(77-152) PCNA CDC6 Unwound forkorigin of replication PCNA RFC4 PSME2 PRIM2 origin of replication PSMB6 p-CDC6Replication Fork UBB(153-228) POLE GINS1 ORC2 UBC(305-380) RNA primer:originduplex:DNApolymerasealpha:primasecomplexPOLD1 RFC5 dCTPUBB(153-228) ATP UBB(153-228) POLE4 PSMC5 UBC(609-684) UBC(381-456) MCM5 CDC6 Flap POLD4 POLA2 ubiquitinated Cdc6PCNA ORC3 MCM6 PSMB10 MCM6 PSMA7 GINS3 UBC(229-304) UBC(457-532) POLD3 POLA2 origin of replication ATPORC1 MCM4 Processivecomplex:Okazakifragment:Flap:RPAheterotrimer:dna2MCM7 p-T160-CDK2 DNA primer PSMB4 PRIM2 MCM4 CDKN1A PRIM1 RFC3 PSMB7 PRIM1 MCM5 MCM2 MCM7 PSMD14 UBC(229-304) Flap PRIM1 Okazaki fragment minus Flap PCNA PRIM2 PSMD5 MCM6 PRIM1 UBC(1-76) PSMC4 PSME1 pre-replicativecomplexRNA primer ubiquitinated Orc1MCM8 POLA1 origin of replication MCM4 DNA primer POLD1 UBC(77-152) POLA1 UBC(533-608) POLA1 PSMA2 PSMC1 MCM2Unwinding complex atreplication forkORC6 PSMD11 MCM5POLA2 UBC(533-608) POLA1 POLD4 POLA1 RPA1 UBC(153-228) PSMF1 ligated okazakifragmentUBC(609-684) RFC4 UBB(1-76) ORC1 POLD2 GINS2PSMB1 POLD3 RFC1 UBC(457-532) CCNA2 GINS3POLA2 PRIM2 origin of replication POLA2 ADPDNA primer MCM6 DNA polymerasealpha:primase:DNApolymerasealpha:origincomplexATPProcessivecomplex:Okazakifragment:Flap:RPAheterotrimerPOLA1 POLD3 PSMD1 UBC(229-304) RPA2 RFC3 UBB(77-152) POLD1 POLA2 POLA2 ADPPRIM2 Okazaki fragment PSMD9 UBC(609-684) PRIM1 origin of replication PSMB2 UBA52(1-76) SHFM1 UBB(1-76) RPS27A(1-76) RNA primer-DNAprimer:originduplexRFC2 UTP Processivecomplex:nicked DNAfrom adjacentOkazaki fragmentsORC4 RFC HeteropentamerPRIM2 GINS2 UBC(457-532) origin of replication Okazaki fragment UBC(381-456) UBC(533-608) POLD1 PRIM2 UBC(77-152) GTP PSMC2 ATPUBC(77-152) UbPRIM2 PRIM1 RNA primer POLD3 PSMB8 PSMD10 POLD2 POLD2 AMPPOLA2 RFC2 PSMD12 GINS1 PSMB9 POLA1 UBC(305-380) POLA1 PSMD3 GINS3 UBA52(1-76) PSMA5 RB1 PCNA homotrimerPOLD1 DNA primer Processive complexDNA polymeraseepsilonPOLD4 UBC(381-456) POLD2 origin of replication PRIM1 CDC6 RPS27A(1-76) CDT1 UBC(533-608) PSMD13 POLA1 origin of replication PSMB5 POLE4 UBC(305-380) LIG1MCM3 POLD3 Flap PRIM1 UBB(77-152) PSME3 POLA2 CDC6POLD4 RFCHeteropentamer:RNAprimer-DNAprimer:originduplex:PCNAhomotrimerMCM3 POLA1 MCM4 Remaining Flap PCNA origin of replication DNA2 CMPMcm4,6,7 complexUBC(305-380) POLA2 DNA primer PRIM2 Ubp-CDC6ORC4 PRIM2 UBC(153-228) POLD2 POLA2 RFC4 UBC(1-76) ORC6 RNA primer-DNAprimer:originduplex:PCNARNA primer POLD2 MCM5 POLA2 Processivecomplex:Okazakifragments:RemainingFlaporigin of replication CDT1 PRIM2 UBC(381-456) UBB(1-76) POLD2 GINS1RPS27A(1-76) PCNA CDKPOLD1 Okazaki fragment NTPGINS complexRPA3 MCM2 ORC5 PSMC6 POLE3 ORC3 MCM7 UBC(1-76) POLD1 PSMA3 MCM2-7DNA primer cyclin Okazaki fragmentGINS4 UBC(457-532) UMPPOLA2 PRIM1 DNA primer origin of replication UBB(1-76) PSMA8 UBC(1-76) ORC2 FZR1 PCNA RPA1 MCM2 MCM5 origin of replication PSMB3 MCM7 UBA52(1-76) CDK2 POLE2 RNA primer POLA1 POLD2 PSME4 dGTPPOLD4 12, 273430, 37926308, 13152624


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: 61

Quality Tags

Ontology Terms

 

Bibliography

View all...
  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
  2. 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
  3. Liu L, Mo J, Rodriguez-Belmonte EM, Lee MY.; ''Identification of a fourth subunit of mammalian DNA polymerase delta.''; PubMed
  4. 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
  5. Brown WC, Campbell JL.; ''Interaction of proliferating cell nuclear antigen with yeast DNA polymerase delta.''; PubMed
  6. 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
  7. 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
  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. Hubscher U, Maga G, Spadari S.; ''Eukaryotic DNA polymerases.''; PubMed
  10. Harrington JJ, Lieber MR.; ''DNA structural elements required for FEN-1 binding.''; PubMed
  11. Chang LM, Rafter E, Augl C, Bollum FJ.; ''Purification of a DNA polymerase-DNA primase complex from calf thymus glands.''; PubMed
  12. Zachariae W, Nasmyth K.; ''Whose end is destruction: cell division and the anaphase-promoting complex.''; PubMed
  13. Li Y, Pursell ZF, Linn S.; ''Identification and cloning of two histone fold motif-containing subunits of HeLa DNA polymerase epsilon.''; PubMed
  14. 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
  15. 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
  16. Nethanel T, Zlotkin T, Kaufmann G.; ''Assembly of simian virus 40 Okazaki pieces from DNA primers is reversibly arrested by ATP depletion.''; PubMed
  17. 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
  18. Schaarschmidt D, Ladenburger EM, Keller C, Knippers R.; ''Human Mcm proteins at a replication origin during the G1 to S phase transition.''; PubMed
  19. Lee SH, Hurwitz J.; ''Mechanism of elongation of primed DNA by DNA polymerase delta, proliferating cell nuclear antigen, and activator 1.''; PubMed
  20. Maga G, Stucki M, Spadari S, Hübscher U.; ''DNA polymerase switching: I. Replication factor C displaces DNA polymerase alpha prior to PCNA loading.''; PubMed
  21. 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
  22. Waga S, Bauer G, Stillman B.; ''Reconstitution of complete SV40 DNA replication with purified replication factors.''; 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. Jiang W, Wells NJ, Hunter T.; ''Multistep regulation of DNA replication by Cdk phosphorylation of HsCdc6.''; PubMed
  25. Hindges R, Hübscher U.; ''DNA polymerase delta, an essential enzyme for DNA transactions.''; PubMed
  26. 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
  27. Harper JW, Burton JL, Solomon MJ.; ''The anaphase-promoting complex: it's not just for mitosis any more.''; PubMed
  28. 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
  29. 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
  30. 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
  31. Mossi R, Hübscher U.; ''Clamping down on clamps and clamp loaders--the eukaryotic replication factor C.''; PubMed
  32. Lee MY, Tan CK, So AG, Downey KM.; ''Purification of deoxyribonucleic acid polymerase delta from calf thymus: partial characterization of physical properties.''; PubMed
  33. Bae SH, Bae KH, Kim JA, Seo YS.; ''RPA governs endonuclease switching during processing of Okazaki fragments in eukaryotes.''; PubMed
  34. 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
  35. Harrington JJ, Lieber MR.; ''The characterization of a mammalian DNA structure-specific endonuclease.''; PubMed
  36. 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
  37. Voges D, Zwickl P, Baumeister W.; ''The 26S proteasome: a molecular machine designed for controlled proteolysis.''; PubMed
  38. Bambara RA, Murante RS, Henricksen LA.; ''Enzymes and reactions at the eukaryotic DNA replication fork.''; PubMed

History

View all...
CompareRevisionActionTimeUserComment
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)
AMPMetaboliteCHEBI:16027 (ChEBI)
ATP MetaboliteCHEBI:15422 (ChEBI)
ATPMetaboliteCHEBI:15422 (ChEBI)
CCNA1 ProteinP78396 (Uniprot-TrEMBL)
CCNA2 ProteinP20248 (Uniprot-TrEMBL)
CDC45 ProteinO75419 (Uniprot-TrEMBL)
CDC45ProteinO75419 (Uniprot-TrEMBL)
CDC6 ProteinQ99741 (Uniprot-TrEMBL)
CDC6ProteinQ99741 (Uniprot-TrEMBL)
CDK2 ProteinP24941 (Uniprot-TrEMBL)
CDKN1A ProteinP38936 (Uniprot-TrEMBL)
CDKN1B ProteinP46527 (Uniprot-TrEMBL)
CDKComplexR-HSA-68380 (Reactome)
CDT1 ProteinQ9H211 (Uniprot-TrEMBL)
CMPMetaboliteCHEBI:17361 (ChEBI)
CTP MetaboliteCHEBI:17677 (ChEBI)
Cyclin

A:Cdk2:substrate

complex
ComplexR-HSA-187947 (Reactome)
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-NUL-68424 (Reactome)
DNA2 ProteinP51530 (Uniprot-TrEMBL)
DNA2ProteinP51530 (Uniprot-TrEMBL)
FEN1ProteinP39748 (Uniprot-TrEMBL)
FZR1 ProteinQ9UM11 (Uniprot-TrEMBL)
Flap R-NUL-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-NUL-68452 (Reactome)
Okazaki fragment minus Flap R-NUL-68469 (Reactome)
Okazaki fragmentR-NUL-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)
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)
RB1 ProteinP06400 (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-NUL-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-NUL-68467 (Reactome)
Replication Fork R-NUL-169515 (Reactome)
Replication ForkR-NUL-169515 (Reactome)
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)
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-NUL-169509 (Reactome)
anaphase-promoting complex (APC)R-HSA-69007 (Reactome)
cyclin R-HSA-68379 (Reactome)
dATPMetaboliteCHEBI:16284 (ChEBI)
dCTPMetaboliteCHEBI:16311 (ChEBI)
dGTPMetaboliteCHEBI:16497 (ChEBI)
dTTPMetaboliteCHEBI:18077 (ChEBI)
ligated okazaki fragmentR-NUL-69172 (Reactome)
origin of replication R-NUL-68419 (Reactome)
p-CDC6ProteinQ99741 (Uniprot-TrEMBL)
p-S,T-ORC1ProteinQ13415 (Uniprot-TrEMBL)
p-T160-CDK2 ProteinP24941 (Uniprot-TrEMBL)
pre-replicative

complex

(Orc1-minus)
ComplexR-HSA-157563 (Reactome)
pre-replicative complexComplexR-HSA-68559 (Reactome)
ubiquitinated Cdc6ComplexR-HSA-68570 (Reactome)
ubiquitinated Orc1ComplexR-HSA-113570 (Reactome)
ubiquitinated Orc1ComplexR-HSA-68586 (Reactome)

Annotated Interactions

View all...
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)
CDC45R-HSA-176942 (Reactome)
CDC6R-HSA-69005 (Reactome)
CDKmim-catalysisR-HSA-69005 (Reactome)
CMPArrowR-HSA-69144 (Reactome)
Cyclin

A:Cdk2:substrate

complex
mim-catalysisR-HSA-68944 (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)
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)
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) At the beginning of this reaction, 1 molecule of 'ubiquitin', and 1 molecule of 'phosphorylated Orc1' are present. At the end of this reaction, 1 molecule of 'ubiquitinated Orc1' is present.

This reaction takes place in the 'nucleus'.

R-HSA-68947 (Reactome) In this reaction, 1 molecule of 'ubiquitinated Orc1' is translocated from nucleoplasm to cytosol.

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

R-HSA-68948 (Reactome) At the beginning of this reaction, 1 molecule of 'ubiquitinated Orc1' 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-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.
R-HSA-69074 (Reactome) The loading of proliferating cell nuclear antigen (PCNA) leads to recruitment of pol delta, the process of polymerase switching. Human PCNA is a homotrimer of 36 kDa subunits that form a toroidal structure. The loading of PCNA by RFC is a key event in the transition from the priming mode to the extension mode of DNA synthesis. The processive complex is composed of the pol delta holoenzyme and PCNA (Murakami et al.2010).