DNA replication

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High fidelity DNA synthesis is beneficial for maintaining genetic information over many generations and for avoiding mutations that can initiate and promote human diseases such as cancer and neurodegenerative diseases. Low fidelity DNA synthesis is beneficial for the evolution of species, for generating diversity leading to increased survival of viruses and microbes when subjected to changing environments, and for the development of a normal immune system.

A complex network of interacting proteins and enzymes is required for DNA replication. Generally, DNA replication follows a multistep enzymatic pathway. At the DNA replication fork, a DNA helicase (DnaB or MCM complex) precedes the DNA synthetic machinery and unwinds the duplex parental DNA in cooperation with the SSB or RPA. On the leading strand, replication occurs continuously in a 5 to 3 direction, whereas on the lagging strand, DNA replication occurs discontinuously by synthesis and joining of short Okazaki fragments. In prokaryotes, the leading strand replication apparatus consists of a DNA polymerase (pol III core), a sliding clamp (beta), and a clamp loader (gamma delta complex). The DNA primase (DnaG) is needed to form RNA primers. Normally, during replication of the lagging-strand DNA template, an RNA primer is removed either by an RNase H or by the 5 to 3 exonuclease activity of DNA pol I, and the DNA ligase joins the Okazaki fragments. In eukaryotes, three DNA polymerases (alpha, delta, and epsilon) have been identified. DNA primase forms a permanent complex with DNA polymerase alpha. PCNA and RFC function as a clamp and a clamp loader. FEN 1 and RNase H1 remove the RNA from the Okazaki fragments and DNA ligase I joins the DNA.

EXTERNAL DATABASES:
KEGG database - DNA replication - Homo sapiens (human) 
KEGG database - DNA replication - Mus musculus (mouse)
KEGG database - DNA replication - Caenorhabditis elegans (nematode)
KEGG database - DNA replication - Drosophila melanogaster (fruit fly)
KEGG database - DNA replication - Saccharomyces cerevisiae (budding yeast) 
KEGG database - DNA replication - DNA replication - Schizosaccharomyces pombe (fission yeast)
KEGG database - DNA replication - Escherichia coli K-12 MG1655
KEGG database - DNA replication - Arabidopsis thaliana (thale cress)


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ORTHOLOGY CLASS Homo sapiens L. (human) [HSA] Mus musculus L. (mouse) [MMU] Caenorhabditis elegans Maupas (nematode) [CEL] Drosophila melanogaster Meigen (fruit fly) [DME] Saccharomyces cerevisiae Meyen ex E.C. Hansen (budding yeast) [SCE] Schizo-saccharomyces pombe Lindner (fission yeast) [SPO] Escherichia coli Migula (bacterium) K-12 MG1655 [ECO] Arabidopsis thaliana (L.) Heynh. (mouse-ear cress) [ATH]
ko:K03656 (ATP-dependent DNA helicase Rep [EC:3.6.4.12]) Rep
ko:K11273 (chromosome transmission fidelity protein 1 [EC:3.6.4.13]) helicase DDX11 (CHLR1)
ko:K07478 (putative ATPase) ATPase WRNIP1
ko:K10756 (replication factor C subunit 3/5) RFC3
RFC5
Rfc5
Rfc3
rfc-3
ARPA
RfC3
RfC38
RFC3
RFC5
rfc3
rfc5
RFC3
putative RFC3/5
ko:K10755 (replication factor C subunit 2/4) RFC2
RFC4
Rfc4
Rfc2
rfc-4
rfc-2
RfC4
CG8142
RFC2
RFC4
rfc2
rfc4
RFC2/4
RFC2
ko:K10754 (replication factor C subunit 1) RFC1 Rfc1 rfc-1 Gnf1 RFC1 rfc1 AtRFC1
ko:K10747 (DNA ligase 1 [EC:6.5.1.1]) LIG1 Lig1 lig-1 DmDNA Lig I CDC9 adl1
cdc17
At1g49250
ATLIG1
ko:K10745 (ribonuclease H2 subunit C) RNASEH2C Rnaseh2c Dmel_CG30105 SPAC12B10.15c At2g39440
ko:K10744 (ribonuclease H2 subunit B) RNASEH2B Rnaseh2b RnaseH2B DMel_CG11164 (RnaseH2B hp) putative Rnh2B putative RnaseH2b
ko:K10743 (ribonuclease H2 subunit A [EC:3.1.26.4]) RNASEH2A Rnaseh2a rnh-2 RNase H2 subunit A RNH201 rnh201 RNase H2 subunit A
ko:K10742 (DNA replication ATP-dependent helicase Dna2 [EC:3.6.4.12]) DNA2 Dna2 dna-2 Dmel_CG2990 DNA2 dna2 Dna2
ko:K10741 (replication factor A4) RPA4
ko:K10740 (replication factor A3) RPA3 Rpa3 Dmel_CG15220 ssb3 At4g18590
F3C22_30
ko:K10739 (replication factor A2) RPA2 Rpa2 rpa-2
rpa-4
RPA2 RFA2 ssb2 RPA2
RPA32B
ko:K07466 (replication factor A1) RPA1 Rpa1 rpa-1 RpA-70 RFA1 ssb1 RPA1A
ko:K04802 (proliferating cell nuclear antigen) PCNA Pcna pcn-1 Mus209 (Pcna)
Pcna2
POL30 pcn1 PCNA1
PCNA2
ko:K04799 (flap endonuclease-1 [EC:3.-.-.-]) FEN1 (DNase IV) Fen1 crn-1 Fen1 RAD27 rad2 AT5G26680
ko:K03506 (DNA polymerase epsilon subunit 4 [EC:2.7.7.7]) POLE4 Pole4 DNA Pol epsilon sub 4 Mes4 DPB3 SPCC16C4.22
ko:K03505 (DNA polymerase delta subunit 4) POLD4 Pold4 cdm1 POLD4
ko:K03504 (DNA polymerase delta subunit 3) POLD3 Pold3 PolD3 CG3975
Dmel_CG3975
POL32 cdc27 POLD3
ko:K03470 (ribonuclease HII [EC:3.1.26.4]) rnhB
ko:K03469 (ribonuclease HI [EC:3.1.26.4]) RNASEH1 Rnaseh1 rnh-1.3
rnh-1.0
rnh1 RNH1 rnh1 rnhA
ko:K03111 (single-strand DNA-binding protein) SSBP1 Ssbp1 mtSSB Ssb At3g18580
ko:K02685 (DNA primase large subunit [EC:2.7.7.-]) PRIM2 Prim2 pri-2 DNApol-alpha60 PRI2 spp2 At1g67320
ko:K02684 (DNA primase small subunit [EC:2.7.7.-]) PRIM1 Prim1 Pri-1 DNApol-alpha50 PRI1 spp1 POLA3
ko:K02542 (minichromosome maintenance protein 6) MCM6 Mcm6 mcm-6 Mcm6 MCM6 mcm6 MCM6
ko:K02541 (minichromosome maintenance protein 3) MCM3 Mcm3 mcm-3 Mcm3 MCM3 mcm3 MCM3
ko:K02540 (minichromosome maintenance protein 2) MCM2 Mcm2 mcm-2 Mcm2 MCM2 mcm2 MCM2
ko:K02345 (DNA polymerase III subunit theta [EC:2.7.7.7]) HolE
ko:K02344 (DNA polymerase III subunit psi [EC:2.7.7.7]) HolD
ko:K02343 (DNA polymerase III subunit gamma/tau [EC:2.7.7.7]) DnaX
ko:K02342 (DNA polymerase III subunit epsilon [EC:2.7.7.7]) DnaQ
ko:K02341 (DNA polymerase III subunit delta' [EC:2.7.7.7]) HolB
ko:K02340 (DNA polymerase III subunit delta [EC:2.7.7.7]) HolA
ko:K02339 (DNA polymerase III subunit chi [EC:2.7.7.7]) HolC
ko:K02338 (DNA polymerase III subunit beta [EC:2.7.7.7]) DnaN
ko:K02337 (DNA polymerase III subunit alpha [EC:2.7.7.7]) DnaE (PolC)
ko:K02335 (DNA polymerase I [EC:2.7.7.7]) DNA Pol I POLGAMMA2
POLGAMMA1
ko:K02328 (DNA polymerase delta subunit 2) POLD2 Pold2 DNA Pol delta sub 2 DNA pol delta small sub POL31 cdc1 POLD2
ko:K02327 (DNA polymerase delta subunit 1 [EC:2.7.7.7]) POLδ (POLD) mPolδ (mPolD) DNA Pol delta DNApol-delta POL3
POL3
cdc6 POLD1
ko:K02326 (DNA polymerase epsilon subunit 3 [EC:2.7.7.7]) POLE3 Pole3 Chrac-14 DPB4 dpb4
ko:K02325 (DNA polymerase epsilon subunit 2 [EC:2.7.7.7]) POLE2 Pole2 DNA Pole-2 Pole2 DPB2 dpb2 ATDPB2
ko:K02324 (DNA polymerase epsilon subunit 1 [EC:2.7.7.7]) POLε (POLE) mPolε (mPolE) DNA Pol epsilon sub 1 (hypothetical protein) DNApol-epsilon POL2 cdc20 TIL1
TIL2
ko:K02321 (DNA polymerase alpha subunit B) POLA2 Pola2 div-1 DNApol-alpha73 POL12 spb70 POLA2
ko:K02320 (DNA polymerase alpha subunit A [EC:2.7.7.7]) POLα (POLA) mPolα (mPolA) DNA pol DNApol-alpha180 POL1 pol1 ICU2
ko:K02316 (DNA primase [EC:2.7.7.-]) dnaG
ko:K02314 (replicative DNA helicase [EC:3.6.4.12]) dnaB
ko:K02212 (minichromosome maintenance protein 4 (cell division control protein 54)) MCM4 Mcm4 mcm-4 dpa MCM4 cdc21 MCM4
ko:K02210 (minichromosome maintenance protein 7 (cell division control protein 47)) MCM7 Mcm7 mcm-7 Mcm7 MCM7
MCM7
mcm7 PRL
ko:K02209 (minichromosome maintenance protein 5 (cell division control protein 46)) MCM5 Mcm5 mcm-5 Mcm5 MCM5 MCM5
ko:K01972 (DNA ligase (NAD+) [EC:6.5.1.2]) DNA ligase I
DNA ligase B
ko:K06223 (DNA adenine methylase [EC:2.1.1.72]) Dam
ko:K03169 (DNA topoisomerase III [EC:5.99.1.2]) TopB
ko:K03168 (DNA topoisomerase I [EC:5.99.1.2]) TopA
ko:K02622 (topoisomerase IV subunit B [EC:5.99.1.-]) ParE
ko:K02621 (topoisomerase IV subunit A [EC:5.99.1.-]) ParC
ko:K02470 (DNA gyrase subunit B [EC:5.99.1.3]) GyrB GYRB1
GYRBM
ko:K02469 (DNA gyrase subunit A [EC:5.99.1.3]) GyrA GYRA
ko:K03165 (DNA topoisomerase III [EC:5.99.1.2]) TOP3B
TOP3A
Top3b
Top3a
top-3
Top-3
Top3alpha
Top3beta
TOP3 top3 TOP3A
ko:K03164 (DNA topoisomerase II [EC:5.99.1.3]) TOP2B
TOP2A
Top2b
Top2a
TopII
Y46H3C.4
top-2
cin-4
Top2 TOP2 top2 TOPII
ko:K03163 (DNA topoisomerase I [EC:5.99.1.2]) TOP1mt
TOP1
Top1
Top1mt
top-1 Top1 TOP1 top1 TOP1BETA
TOP1
ko:K00558 (DNA (cytosine-5-)-methyltransferase [EC:2.1.1.37]) DNMT3L
DNMT3B
DNMT1
DNMT3A
Dnmt1
Dnmt3b
Dnmt3l
Dnmt3a
Dcm CMT3
CMT1
AT4G08990
MEE57
DMT2
CMT2
MET1
ko:K02333 (DNA polymerase gamma 2) POLG2 Polg2 DNApol-gamma35
ko:K02332 (DNA polymerase gamma 1 [EC:2.7.7.7]) POLγ (POLG) Polg Polg-1 tam MIP1 pog1
ko:K10735 (GINS complex subunit 4) GINS4 Gins4 Y113G7B.24a Sld5 SLD5 sld5 SLD5
ko:K10734 (GINS complex subunit 3) GINS3 Gins3 Y65B4BR.8 Psf3 PSF3 psf3 PSF3
ko:K10733 (GINS complex subunit 2) GINS2 Gins2 F31C3.5 Psf2 PSF2 psf2 PSF2
ko:K10732 (GINS complex subunit 1) GINS1 Gins1 GINS1 hypothetical protein Psf1 PSF1 Psf1 PSF1

Last modification date: Oct. 11, 2011