Synthesis of DNA (Homo sapiens)

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16, 31, 3216, 20, 22-252433320, 2127351011526-2829, 3012, 1317, 18272714-16196cytosolnucleoplasmMcm4,6,7 complexProcessive complex:Okazaki fragment:Flap:RPA heterotrimer:dna2Mcm2-7 complexRFC Heteropentamerdna2 endonucleaseADPPCNA homotrimerdATPFlap endonuclease-1pre-replicative complex (Orc1-minus)AMPUnwinding complex at replication forkProcessive complex:Okazaki fragment:Flapubiquitin26S proteasomeRFC Heteropentamer:RNA primer-DNA primer:origin duplexligated okazaki fragmentRNA primer-DNA primer:origin duplex:PCNACDKphosphorylated Orc1Processive complex:nicked DNA from adjacent Okazaki fragmentsNTPUMPdGTPMcm2Mcm3phosphorylated Cdc6PSF3pPSF2pATPCdc45RPA heterotrimerSLD5Panaphase-promoting complex (APC)ADPATPReplication ForkRNA primer:origin duplex:DNA polymerase alpha:primase complexubiquitinated Orc1dTTPubiquitinDNA ligase IDNA Polymerase delta tetramerDNA polymerase epsilonProcessive complex:Okazaki fragment:Flap:RPA heterotrimerProcessive complex:Okazaki fragment complexCyclin A:Cdk2:substrate complexubiquitinated Cdc6dCTPCMPGMPPSF1pADPProcessive complex:Okazaki fragments:Remaining Flapphosphorylated Cdc6ubiquitinated Orc1ATPRNA primer-DNA primer:origin duplexRFC Heteropentamer:RNA primer-DNA primer:origin duplex:PCNA homotrimerMCM8 (variant 1)DNA polymerase alpha:primase:DNA polymerase alpha:origin complexUnwound forkMcm5ATPProcessive complexDNA polymerase alpha:primaseCDC6Okazaki fragmentGINS complexpre-replicative complex36395127, 84


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.

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Ontology Terms

 

Bibliography

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  2. Harrington JJ, Lieber MR.; ''DNA structural elements required for FEN-1 binding.''; PubMed Europe PMC Scholia
  3. 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
  4. 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
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  8. Mossi R, Hübscher U.; ''Clamping down on clamps and clamp loaders--the eukaryotic replication factor C.''; PubMed Europe PMC Scholia
  9. 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
  10. 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
  11. Harrington JJ, Lieber MR.; ''The characterization of a mammalian DNA structure-specific endonuclease.''; PubMed Europe PMC Scholia
  12. 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
  13. Bae SH, Bae KH, Kim JA, Seo YS.; ''RPA governs endonuclease switching during processing of Okazaki fragments in eukaryotes.''; 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. 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
  16. 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
  17. 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
  18. 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
  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 Scholia
  20. 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
  21. 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
  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. Voges D, Zwickl P, Baumeister W.; ''The 26S proteasome: a molecular machine designed for controlled proteolysis.''; PubMed Europe PMC Scholia
  24. 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
  25. Bambara RA, Murante RS, Henricksen LA.; ''Enzymes and reactions at the eukaryotic DNA replication fork.''; PubMed Europe PMC Scholia
  26. 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
  27. 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
  28. 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
  29. 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
  30. 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
  31. 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
  32. 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
  33. 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
  34. Liu L, Mo J, Rodriguez-Belmonte EM, Lee MY.; ''Identification of a fourth subunit of mammalian DNA polymerase delta.''; PubMed Europe PMC Scholia
  35. 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
  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 Europe PMC Scholia
  37. Hindges R, Hübscher U.; ''DNA polymerase delta, an essential enzyme for DNA transactions.''; PubMed Europe PMC Scholia
  38. Hubscher U, Maga G, Spadari S.; ''Eukaryotic DNA polymerases.''; PubMed Europe PMC Scholia
  39. 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
  40. Waga S, Bauer G, Stillman B.; ''Reconstitution of complete SV40 DNA replication with purified replication factors.''; PubMed Europe PMC Scholia

History

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CompareRevisionActionTimeUserComment
115034view16:57, 25 January 2021ReactomeTeamReactome version 75
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

DataNodes

View all...
NameTypeDatabase referenceComment
26S proteasome ComplexREACT_2353 (Reactome)
ADP Metabolite16761 (ChEBI)
AMP Metabolite16027 (ChEBI)
ATP Metabolite15422 (ChEBI)
CDC6 ProteinQ99741 (UniProt)
CDK ComplexREACT_5476 (Reactome)
CMP Metabolite17361 (ChEBI)
Cdc45 ProteinO75419 (UniProt)
Cyclin A:Cdk2:

substrate complex

ComplexREACT_9192 (Reactome)
DNA Polymerase

delta tetramer

ComplexREACT_5801 (Reactome)
DNA ligase I ProteinP18858 (UniProt)
DNA polymerase

alpha:primase

ComplexREACT_3725 (Reactome)
DNA polymerase

alpha:primase:DNA polymerase alpha: origin complex

ComplexREACT_3167 (Reactome)
DNA polymerase

epsilon

ComplexREACT_4621 (Reactome)
Flap endonuclease-1 ProteinP39748 (UniProt)
GINS complex ComplexREACT_7704 (Reactome)
GMP Metabolite17345 (ChEBI)
MCM8 (variant 1) ProteinQ9UJA3-1 (UniProt)
Mcm2 ProteinP49736 (UniProt)
Mcm2-7 complex ComplexREACT_4763 (Reactome)
Mcm3 ProteinP25205 (UniProt)
Mcm4,6,7 complex ComplexREACT_3276 (Reactome)
Mcm5 ProteinP33992 (UniProt)
NTP MetaboliteREACT_4491 (Reactome)
Okazaki fragment UnknownREACT_4386 (Reactome)
PCNA homotrimer ComplexREACT_2542 (Reactome)
PSF1p ProteinQ14691 (UniProt)
PSF2p ProteinQ9Y248 (UniProt)
PSF3p UnknownREACT_7682 (Reactome)
Processive complex ComplexREACT_3120 (Reactome)
Processive complex:

Okazaki fragment complex

ComplexREACT_5537 (Reactome)
Processive complex:

Okazaki fragment: Flap

ComplexREACT_4984 (Reactome)
Processive complex:

Okazaki fragment: Flap:RPA heterotrimer

ComplexREACT_4699 (Reactome)
Processive complex:

Okazaki fragment: Flap:RPA heterotrimer:dna2

ComplexREACT_3597 (Reactome)
Processive complex:

Okazaki fragments: Remaining Flap

ComplexREACT_4338 (Reactome)
Processive complex:

nicked DNA from adjacent Okazaki fragments

ComplexREACT_4371 (Reactome)
RFC

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

ComplexREACT_5474 (Reactome)
RFC Heteropentamer ComplexREACT_4881 (Reactome)
RFC Heteropentamer:

RNA primer-DNA primer:origin duplex

ComplexREACT_5241 (Reactome)
RNA primer-DNA

primer:origin duplex:PCNA

ComplexREACT_4810 (Reactome)
RNA primer-DNA

primer:origin duplex

ComplexREACT_5497 (Reactome)
RNA primer:origin

duplex:DNA polymerase alpha: primase complex

ComplexREACT_5709 (Reactome)
RPA heterotrimer ComplexREACT_3427 (Reactome)
Replication Fork UnknownREACT_7812 (Reactome)
SLD5P ProteinQ9BRT9 (UniProt)
UMP Metabolite16695 (ChEBI)
Unwinding complex

at replication fork

ComplexREACT_7007 (Reactome)
Unwound fork UnknownREACT_7610 (Reactome)
anaphase-promoting

complex (APC)

UnknownREACT_3388 (Reactome)
dATP Metabolite16284 (ChEBI)
dCTP Metabolite16311 (ChEBI)
dGTP Metabolite16497 (ChEBI)
dTTP Metabolite18077 (ChEBI)
dna2 endonuclease ProteinP51530 (UniProt)
ligated okazaki

fragment

UnknownREACT_4394 (Reactome)
phosphorylated

Cdc6

ProteinQ99741 (UniProt)
phosphorylated Orc1 ProteinQ13415 (UniProt)
pre-replicative

complex

ComplexREACT_4388 (Reactome)
pre-replicative

complex (Orc1- minus)

ComplexREACT_3695 (Reactome)
ubiquitin ProteinREACT_3316 (Reactome)
ubiquitin ProteinREACT_3995 (Reactome)
ubiquitinated Cdc6 ComplexREACT_5308 (Reactome)
ubiquitinated Orc1 ComplexREACT_5173 (Reactome)
ubiquitinated Orc1 ComplexREACT_5402 (Reactome)

Annotated Interactions

No annotated interactions

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