DNA replication (Homo sapiens)

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Pre-replicative complexDegraded by proteasome in cytosolOrc complex2. Activation of the pre-replicative complexCdt1Orc complexOrc5Mcm4Mcm5Mcm74. Switching of origins to post-replicative stateRFC40GemininCdc6Orc2Mcm10Cdt1Phosphorylated Cdc6Mcm2Orc2Orc1RFC36RFC38Orc complexRNA primer-DNA primerCdt1Phosphorylation ofMcm 2-7 complexMcm7UbiquitinPhosphorylated Orc1DNA polymerase alpha:primase: origin complexRFC140Orc2Orc complexRFC Heteropentamer:RNA primer-DNA primerPCNA homotrimerOrc5Orc4Pre-replicative complexOrc4Cdt1Orc5Mcm6DNAPolymerase Ap70Mcm 4,6,7 trimer forms andassociates with the replication forkRFC37p180OriginMcm3p49Degraded byproteasomein cytosolMcm6Mcm2Mcm10Orc3UbiquitinUbiquitinated Orc1Processive complexOrc3PrimaseRFC Heteropentamer:RNA primer-DNA primerOrc3Mcm31. Assembly of the pre-replicative complexOrc complexDNA polymerase alpha:primase: origin complexCdc63. DNA replication initiationCdc6Cdc6p585. Leading/lagging strand synthesisOrc2Cdt1Mcm4RNA primer-DNA primer:origin duplex:PCNAOrc3RNA PrimerUbiquitinated Cdc6RNA primer-DNA primerMcm5CDC45LMCM2ASKCTPRFC2ADPPOLD3UBA52ADPCDK2ORC1LdCTPPRIM2AUTPPOLAGMNNCDC6MCM7POLD2RPA1MCM3POLD1CDC7PRIM1dUTPORC6LCDT1ORC2LPOLD4RPA3ORC5LPOLEPOLA2GTPMCM5PCNAMCM6RFC5dGTPRPA2ORC3LRPA4RFC4ATPORC4LPOLE2ATPATPUBCdATPMCM10ATPRFC1MCM4RFC3


Description

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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Bibliography

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

History

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CompareRevisionActionTimeUserComment
128700view16:52, 20 February 2024Khanspersremoved brackets from three groups
117096view11:31, 17 May 2021EweitzModified title
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
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

DataNodes

View all...
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

No annotated interactions

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