ENTRY ko03030 Pathway NAME DNA replication DESCRIPTION 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. CLASS Genetic Information Processing; Replication and repair PATHWAY_MAP ko03030 DNA replication ORTHOLOGY K02345 DNA polymerase III subunit theta [EC:2.7.7.7] K02342 DNA polymerase III subunit epsilon [EC:2.7.7.7] K14159 ribonuclease HI / DNA polymerase III subunit epsilon [EC:3.1.26.4 2.7.7.7] K02337 DNA polymerase III subunit alpha [EC:2.7.7.7] K03763 DNA polymerase III subunit alpha, Gram-positive type [EC:2.7.7.7] K02343 DNA polymerase III subunit gamma/tau [EC:2.7.7.7] K02341 DNA polymerase III subunit delta' [EC:2.7.7.7] K02340 DNA polymerase III subunit delta [EC:2.7.7.7] K02344 DNA polymerase III subunit psi [EC:2.7.7.7] K02339 DNA polymerase III subunit chi [EC:2.7.7.7] K02338 DNA polymerase III subunit beta [EC:2.7.7.7] K02314 replicative DNA helicase [EC:5.6.2.3] K02316 DNA primase [EC:2.7.7.101] K03111 single-strand DNA-binding protein K03469 ribonuclease HI [EC:3.1.26.4] K22316 ribonuclease H / adenosylcobalamin/alpha-ribazole phosphatase [EC:3.1.26.4 3.1.3.73] K03470 ribonuclease HII [EC:3.1.26.4] K03471 ribonuclease HIII [EC:3.1.26.4] K02335 DNA polymerase I [EC:2.7.7.7] K01972 DNA ligase (NAD+) [EC:6.5.1.2] K02319 DNA polymerase, archaea type [EC:2.7.7.7] K02323 DNA polymerase II small subunit [EC:2.7.7.7] K02322 DNA polymerase II large subunit [EC:2.7.7.7] K10726 replicative DNA helicase Mcm [EC:5.6.2.3] K02683 DNA primase small subunit [EC:2.7.7.102] K18882 DNA primase large subunit K07466 replication factor A1 K04802 proliferating cell nuclear antigen K04801 replication factor C small subunit K04800 replication factor C large subunit K10742 DNA replication ATP-dependent helicase/nuclease Dna2 [EC:5.6.2.3 3.1.-.-] K04799 flap endonuclease-1 [EC:3.1.-.-] K10747 DNA ligase 1 [EC:6.5.1.1 6.5.1.6 6.5.1.7] K02320 DNA polymerase alpha subunit A [EC:2.7.7.7] K02321 DNA polymerase alpha subunit B K02684 DNA primase small subunit [EC:2.7.7.102] K02685 DNA primase large subunit K02327 DNA polymerase delta subunit 1 [EC:2.7.7.7] K02328 DNA polymerase delta subunit 2 K03504 DNA polymerase delta subunit 3 K03505 DNA polymerase delta subunit 4 K02324 DNA polymerase epsilon subunit 1 [EC:2.7.7.7] K02325 DNA polymerase epsilon subunit 2 [EC:2.7.7.7] K02326 DNA polymerase epsilon subunit 3 [EC:2.7.7.7] K03506 DNA polymerase epsilon subunit 4 [EC:2.7.7.7] K02540 DNA replication licensing factor MCM2 [EC:5.6.2.3] K02541 DNA replication licensing factor MCM3 [EC:5.6.2.3] K02212 DNA replication licensing factor MCM4 [EC:5.6.2.3] K02209 DNA replication licensing factor MCM5 [EC:5.6.2.3] K02542 DNA replication licensing factor MCM6 [EC:5.6.2.3] K02210 DNA replication licensing factor MCM7 [EC:5.6.2.3] K10739 replication factor A2 K10741 replication factor A4 K10740 replication factor A3 K10754 replication factor C subunit 1 K10755 replication factor C subunit 2/4 K10756 replication factor C subunit 3/5 K10743 ribonuclease H2 subunit A [EC:3.1.26.4] K10744 ribonuclease H2 subunit B K10745 ribonuclease H2 subunit C REFERENCE PMID:8087839 AUTHORS Stillman B. TITLE Smart machines at the DNA replication fork. JOURNAL Cell 78:725-8 (1994) DOI:10.1016/S0092-8674(94)90362-X REFERENCE PMID:9759502 AUTHORS Waga S, Stillman B. TITLE The DNA replication fork in eukaryotic cells. JOURNAL Annu Rev Biochem 67:721-51 (1998) DOI:10.1146/annurev.biochem.67.1.721 ///