DNA replication (WP466)

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. Proteins on this pathway have targeted assays available via the [https://assays.cancer.gov/available_assays?wp_id=WP466 CPTAC Assay Portal]
last edited


Kdahlquist, MaintBot, Khanspers, Thomas, D.Koren, Zari, Mkutmon, AlexanderPico, Egonw, DeSl, and Eweitz

Cited In


Homo sapiens



Pathway Ontology: DNA replication pathway


Label Type Compact Identifier
ADP Metabolite cas:58-64-0
ORC5L GeneProduct ncbigene:5001
RFC1 GeneProduct ncbigene:5981
POLD2 GeneProduct ncbigene:5425
RFC4 GeneProduct ncbigene:5984
UTP Metabolite chebi:15713
RPA1 GeneProduct ncbigene:6117
PCNA GeneProduct ncbigene:5111
dGTP Metabolite cas:2564-35-4
ORC6L GeneProduct ncbigene:23594
MCM5 GeneProduct ncbigene:4174
CDC45L GeneProduct ncbigene:8318
CDC7 GeneProduct ncbigene:8317
GMNN GeneProduct ncbigene:51053
UBC GeneProduct ncbigene:7316
POLD4 GeneProduct ncbigene:57804
MCM6 GeneProduct ncbigene:4175
CDT1 GeneProduct ncbigene:81620
RFC5 GeneProduct ncbigene:5985
RPA4 GeneProduct ncbigene:29935
ASK GeneProduct ncbigene:10926
RPA2 GeneProduct ncbigene:6118
ADP Metabolite cas:58-64-0
POLD1 GeneProduct ncbigene:5424
CTP Metabolite cas:65-47-4
MCM2 GeneProduct ncbigene:4171
CDK2 GeneProduct ncbigene:1017
RPA3 GeneProduct ncbigene:6119
PRIM1 GeneProduct ncbigene:5557
PRIM2A GeneProduct ensembl:ENSG00000146143
ATP Metabolite cas:1927-31-7
ORC2L GeneProduct ncbigene:4999
RFC3 GeneProduct ncbigene:5983
MCM10 GeneProduct ncbigene:55388
POLD3 GeneProduct ncbigene:10714
POLA2 GeneProduct ncbigene:23649
ORC4L GeneProduct ncbigene:5000
MCM7 GeneProduct ncbigene:4176
ATP Metabolite cas:1927-31-7
dATP Metabolite cas:1927-31-7
MCM4 GeneProduct ncbigene:4173
POLE2 GeneProduct ncbigene:5427
UBA52 GeneProduct ncbigene:7311
CDC6 GeneProduct ncbigene:990
ORC3L GeneProduct ncbigene:23595
GTP Metabolite cas:2564-35-4
POLE GeneProduct ncbigene:5426
ATP Metabolite cas:1927-31-7
ORC1L GeneProduct ncbigene:4998
dCTP Metabolite cas:2056-98-6
ATP Metabolite cas:1927-31-7
dUTP Metabolite chebi:17625
RFC2 GeneProduct ncbigene:5982
MCM3 GeneProduct ncbigene:4172
POLA GeneProduct ncbigene:5422


  1. Cimbora DM, Groudine M. The control of mammalian DNA replication: a brief history of space and timing. Cell. 2001 Mar 9;104(5):643–6. PubMed Europe PMC Scholia
  2. Bell SP, Dutta A. DNA replication in eukaryotic cells. Annu Rev Biochem. 2002;71:333–74. PubMed Europe PMC Scholia