DNA Replication (Homo sapiens)

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Orc54. Switching of origins to post-replicative statePrimaseDegraded byproteasomein cytosolRFC Heteropentamer:RNA primer-DNA primerPCNA homotrimerOrc2Cdt1DNA polymerase alpha:primase: origin complexRFC37RNA primer-DNA primer:origin duplex:PCNAMcm4Orc complexMcm 4,6,7 trimer forms andassociates with the replication forkOrc complexOrc complexOriginOrc4Orc complexOrc2Phosphorylation ofMcm 2-7 complex3. DNA replication initiationUbiquitinOrc complexMcm6Orc2Mcm3p70Mcm102. Activation of the pre-replicative complexCdt1p58Mcm5Mcm3Degraded by proteasome in cytosolRNA primer-DNA primerCdc6RFC Heteropentamer:RNA primer-DNA primerMcm2p49Mcm4GemininCdt1Cdc6Orc31. Assembly of the pre-replicative complexPre-replicative complexDNAPolymerase AOrc3Cdc6DNA polymerase alpha:primase: origin complexMcm7RNA PrimerMcm7p180Orc2Mcm6Cdt1Mcm10Mcm5Cdt1Orc5Phosphorylated Orc1RNA primer-DNA primer5. Leading/lagging strand synthesisCdc6Phosphorylated Cdc6Mcm2RFC40Orc4Ubiquitinated Orc1RFC38Pre-replicative complexRFC140RFC36Ubiquitinated Cdc6Orc1UbiquitinOrc3Orc5Processive complexOrc3ATPCDC6RPA4ORC1LGTPRFC5POLD4RPA1ATPPRIM1RFC2dUTPRPA3PRIM2APOLD2CDC7MCM4RPA2UBA52POLEORC4LASKRFC4ORC5LMCM6ATPRFC3dATPADPPOLD3MCM2RFC1CDK2ORC6LCTPUTPUBCdGTPADPCDT1MCM10POLAPOLE2POLA2POLD1GMNNORC3LPCNAMCM5ATPMCM7MCM3ORC2LCDC45LdCTP


Studies in the past decade have suggested that the basic mechanism of DNA replication initiation is conserved in all kingdoms of life. Initiation in unicellular eukaryotes, in particular Saccharomyces cerevisiae (budding yeast), is well understood, and has served as a model for studies of DNA replication initiation in multicellular eukaryotes, including humans. In general terms, the first step of initiation is the binding of the replication initiator to the origin of replication. The replicative helicase is then assembled onto the origin, usually by a helicase assembly factor. Either shortly before or shortly after helicase assembly, some local unwinding of the origin of replication occurs in a region rich in adenine and thymine bases (often termed a DNA unwinding element, DUE). The unwound region provides the substrate for primer synthesis and initiation of DNA replication. The best-defined eukaryotic origins are those of S. cerevisiae, which have well-conserved sequence elements for initiator binding, DNA unwinding and binding of accessory proteins. In multicellular eukaryotes, unlike S. cerevisiae, these loci appear not to be defined by the presence of a DNA sequence motif. Indeed, choice of replication origins in a multicellular eukaryote may vary with developmental stage and tissue type. In cell-free models of metazoan DNA replication, such as the one provided by Xenopus egg extracts, there are only limited DNA sequence specificity requirements for replication initiation. Source description: http://www.reactome.org/content/detail/69306.


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GenMAPP remarks 
Based on www.reactome.org

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102301view20:51, 17 December 2018Khanspersremoved GenMAPP comment
96302view18:25, 7 March 2018EgonwReplaced a secondary ChEBI identifier with a primary identifier.
94886view18:02, 11 October 2017AlexanderPicoReattached interactions to anchors
94885view18:01, 11 October 2017AlexanderPicoReattached interactions to anchors
89897view13:12, 6 October 2016MkutmonModified description
89893view13:09, 6 October 2016MkutmonModified description
89891view13:08, 6 October 2016MkutmonReverted to version '14:46, 29 April 2015' by Mkutmon
89889view13:07, 6 October 2016MkutmonModified description
79981view14:46, 29 April 2015Zari
76196view22:59, 16 June 2014MaintBotminor move - test
70091view18:20, 12 July 2013MaintBotupdating to 2013 schema
41036view23:15, 1 March 2011MaintBotRemoved redundant pathway information and comments
34997view23:26, 9 February 2010KhanspersModified description
34437view18:16, 10 December 2009MaintBotAutomatic update of empty xrefs
32440view17:17, 15 August 2009MaintBotFixed text labels
32113view13:49, 14 August 2009MaintBotFixed group labels
21660view11:32, 14 November 2008MaintBot[[Pathway:Homo sapiens:DNA replication Reactome]] moved to [[Pathway:WP466]]: Moved to stable identifier
13884view13:07, 19 May 2008Thomasadded connectors and merged multi-line labels
13882view13:04, 19 May 2008ThomasWIP on connectors
13880view12:50, 19 May 2008ThomasWIP on connecting lines
13055view11:12, 17 May 2008MaintBotautomated metabolite conversion
12949view10:44, 17 May 2008MaintBotSticky edges patch by Sjoerd
12482view10:24, 15 May 2008ThomasModified categories
11947view00:15, 13 May 2008KhanspersUpdated pathway
7990view13:46, 7 January 2008MaintBot[[Pathway:Human:DNA replication Reactome]] moved to [[Pathway:Homo sapiens:DNA replication Reactome]]: Renaming species
7619view16:04, 18 December 2007MaintBotfixed category names
7209view12:33, 4 November 2007MaintBotAdded categories to GPML
19417view22:17, 22 May 2007D.Korengpml file for [[Human:DNA_replication_Reactome]]
6307view22:17, 22 May 2007Kdahlquistgpml file for [[Human:DNA_replication_Reactome]]

External references


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NameTypeDatabase referenceComment
ADPMetabolite58-64-0 (CAS)
ASKGeneProduct10926 (Entrez Gene)
ATPMetabolite1927-31-7 (CAS)
CDC45LGeneProduct8318 (Entrez Gene)
CDC6GeneProduct990 (Entrez Gene)
CDC7GeneProduct8317 (Entrez Gene)
CDK2GeneProduct1017 (Entrez Gene)
CDT1GeneProduct81620 (Entrez Gene)
CTPMetabolite65-47-4 (CAS)
GMNNGeneProduct51053 (Entrez Gene)
GTPMetabolite2564-35-4 (CAS)
MCM10GeneProduct55388 (Entrez Gene)
MCM2GeneProduct4171 (Entrez Gene)
MCM3GeneProduct4172 (Entrez Gene)
MCM4GeneProduct4173 (Entrez Gene)
MCM5GeneProduct4174 (Entrez Gene)
MCM6GeneProduct4175 (Entrez Gene)
MCM7GeneProduct4176 (Entrez Gene)
ORC1LGeneProduct4998 (Entrez Gene)
ORC2LGeneProduct4999 (Entrez Gene)
ORC3LGeneProduct23595 (Entrez Gene)
ORC4LGeneProduct5000 (Entrez Gene)
ORC5LGeneProduct5001 (Entrez Gene)
ORC6LGeneProduct23594 (Entrez Gene)
PCNAGeneProduct5111 (Entrez Gene)
POLA2GeneProduct23649 (Entrez Gene)
POLAGeneProduct5422 (Entrez Gene)
POLD1GeneProduct5424 (Entrez Gene)
POLD2GeneProduct5425 (Entrez Gene)
POLD3GeneProduct10714 (Entrez Gene)
POLD4GeneProduct57804 (Entrez Gene)
POLE2GeneProduct5427 (Entrez Gene)
POLEGeneProduct5426 (Entrez Gene)
PRIM1GeneProduct5557 (Entrez Gene)
PRIM2AGeneProductENSG00000146143 (Ensembl)
RFC1GeneProduct5981 (Entrez Gene)
RFC2GeneProduct5982 (Entrez Gene)
RFC3GeneProduct5983 (Entrez Gene)
RFC4GeneProduct5984 (Entrez Gene)
RFC5GeneProduct5985 (Entrez Gene)
RPA1GeneProduct6117 (Entrez Gene)
RPA2GeneProduct6118 (Entrez Gene)
RPA3GeneProduct6119 (Entrez Gene)
RPA4GeneProduct29935 (Entrez Gene)
UBA52GeneProduct7311 (Entrez Gene)
UBCGeneProduct7316 (Entrez Gene)
UTPMetabolite15713 (ChEBI)
dATPMetabolite1927-31-7 (CAS)
dCTPMetabolite2056-98-6 (CAS)
dGTPMetabolite2564-35-4 (CAS)
dUTPMetabolite17625 (ChEBI)

Annotated Interactions

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