DNA Replication (Homo sapiens)

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Orc5Orc5Phosphorylated Orc1Mcm 4,6,7 trimer forms andassociates with the replication forkCdt1DNAPolymerase ACdc6Processive complexRFC36RNA primer-DNA primerOrc1Orc complexCdt1p49UbiquitinRFC140Primase5. Leading/lagging strand synthesisMcm5DNA polymerase alpha:primase: origin complexp58Cdc6Orc3Orc3Orc4Orc2Degraded byproteasomein cytosolOrc complexMcm6RFC37Orc5Ubiquitinated Orc1Orc2RFC38Cdt1Mcm5Mcm10Cdt1Mcm6Cdt1Orc2Mcm10Cdc6Cdc6Ubiquitin1. Assembly of the pre-replicative complexOrc4Mcm3Pre-replicative complex3. DNA replication initiationMcm4Orc complexp70Pre-replicative complexRFC Heteropentamer:RNA primer-DNA primerMcm22. Activation of the pre-replicative complexOrc2p180RNA primer-DNA primer:origin duplex:PCNA4. Switching of origins to post-replicative stateOrc3Phosphorylation ofMcm 2-7 complexMcm2OriginRFC40RNA PrimerMcm4Phosphorylated Cdc6Mcm7GemininOrc3Mcm7Degraded by proteasome in cytosolDNA polymerase alpha:primase: origin complexUbiquitinated Cdc6RFC Heteropentamer:RNA primer-DNA primerPCNA homotrimerOrc complexOrc complexMcm3RNA primer-DNA primerORC2LUTPPCNARFC4ATPRPA1PRIM1MCM3UBA52POLD3ASKCDT1dCTPCTPPOLD2MCM5ORC1LMCM2POLA2ADPCDC6ORC4LRFC5ATPUBCRFC2CDC7POLEPOLE2dATPRFC1ATPMCM10dGTPRFC3MCM4ORC6LPOLD4CDC45LORC3LMCM6RPA3GMNNRPA2ATPRPA4ORC5LPOLAPOLD1PRIM2AADPMCM7GTPdUTPCDK2


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. [Kelly & Brown 2000, Bell & Dutta 2002, Marahrens & Stillman 1992, Cimbora & Groudine 2001, Mahbubani et al 1992, Hyrien & Méchali 1993] Source: Reactome (http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=69306)


GenMAPP notes 
GenMAPP remarks 
Based on www.reactome.org

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  1. Cimbora DM, Groudine M; ''The control of mammalian DNA replication: a brief history of space and timing.''; Cell, 2001 PubMed Europe PMC Scholia
  2. Bell SP, Dutta A; ''DNA replication in eukaryotic cells.''; Annu Rev Biochem, 2002 PubMed Europe PMC Scholia


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107180view14:26, 17 September 2019MaintBotChEBI identifier normalization
106374view00:56, 23 August 2019KhanspersModified description
105566view06:22, 9 August 2019KhanspersModified description
104049view16:27, 27 April 2019DeSlAdded new anchor for PCNA
104048view16:21, 27 April 2019DeSlOntology Term : 'DNA replication pathway' added !
104047view16:19, 27 April 2019DeSlAdded references.
102301view20:51, 17 December 2018Khanspersremoved GenMAPP comment
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94886view18:02, 11 October 2017AlexanderPicoReattached interactions to anchors
94885view18:01, 11 October 2017AlexanderPicoReattached interactions to anchors
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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)
PRIM2AGeneProduct5558 (Entrez Gene)
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)
UTPMetabolite9850 (ChEBI)
dATPMetabolite1927-31-7 (CAS)
dCTPMetabolite2056-98-6 (CAS)
dGTPMetabolite2564-35-4 (CAS)
dUTPMetabolite17625 (ChEBI)

Annotated Interactions

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