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 K01972 E6.5.1.2, ligA, ligB; DNA ligase (NAD+) [EC:6.5.1.2] K02209 MCM5, CDC46; DNA replication licensing factor MCM5 [EC:5.6.2.3] K02210 MCM7, CDC47; DNA replication licensing factor MCM7 [EC:5.6.2.3] K02212 MCM4, CDC54; DNA replication licensing factor MCM4 [EC:5.6.2.3] K02314 dnaB; replicative DNA helicase [EC:5.6.2.3] K02316 dnaG; DNA primase [EC:2.7.7.101] K02319 pol; DNA polymerase, archaea type [EC:2.7.7.7] K02320 POLA1; DNA polymerase alpha subunit A [EC:2.7.7.7] K02321 POLA2; DNA polymerase alpha subunit B K02322 polC; DNA polymerase II large subunit [EC:2.7.7.7] K02323 polB; DNA polymerase II small subunit [EC:2.7.7.7] K02324 POLE; DNA polymerase epsilon subunit 1 [EC:2.7.7.7] K02325 POLE2; DNA polymerase epsilon subunit 2 [EC:2.7.7.7] K02326 POLE3; DNA polymerase epsilon subunit 3 [EC:2.7.7.7] K02327 POLD1; DNA polymerase delta subunit 1 [EC:2.7.7.7] K02328 POLD2; DNA polymerase delta subunit 2 K02335 polA; DNA polymerase I [EC:2.7.7.7] K02337 dnaE; DNA polymerase III subunit alpha [EC:2.7.7.7] K02338 dnaN; DNA polymerase III subunit beta [EC:2.7.7.7] K02339 holC; DNA polymerase III subunit chi [EC:2.7.7.7] K02340 holA; DNA polymerase III subunit delta [EC:2.7.7.7] K02341 holB; DNA polymerase III subunit delta' [EC:2.7.7.7] K02342 dnaQ; DNA polymerase III subunit epsilon [EC:2.7.7.7] K02343 dnaX; DNA polymerase III subunit gamma/tau [EC:2.7.7.7] K02344 holD; DNA polymerase III subunit psi [EC:2.7.7.7] K02345 holE; DNA polymerase III subunit theta [EC:2.7.7.7] K02540 MCM2; DNA replication licensing factor MCM2 [EC:5.6.2.3] K02541 MCM3; DNA replication licensing factor MCM3 [EC:5.6.2.3] K02542 MCM6; DNA replication licensing factor MCM6 [EC:5.6.2.3] K02683 priS, pri1, priA; DNA primase small subunit [EC:2.7.7.102] K02684 PRI1; DNA primase small subunit [EC:2.7.7.102] K02685 PRI2; DNA primase large subunit K03111 ssb; single-strand DNA-binding protein K03469 rnhA, RNASEH1; ribonuclease HI [EC:3.1.26.4] K03470 rnhB; ribonuclease HII [EC:3.1.26.4] K03471 rnhC; ribonuclease HIII [EC:3.1.26.4] K03504 POLD3; DNA polymerase delta subunit 3 K03505 POLD4; DNA polymerase delta subunit 4 K03506 POLE4; DNA polymerase epsilon subunit 4 [EC:2.7.7.7] K03763 polC; DNA polymerase III subunit alpha, Gram-positive type [EC:2.7.7.7] K04799 FEN1, RAD2; flap endonuclease-1 [EC:3.1.-.-] K04800 rfcL; replication factor C large subunit K04801 rfcS; replication factor C small subunit K04802 PCNA; proliferating cell nuclear antigen K07466 RFA1, RPA1, rpa; replication factor A1 K10726 mcm; replicative DNA helicase Mcm [EC:5.6.2.3] K10739 RFA2, RPA2; replication factor A2 K10740 RPA3; replication factor A3 K10741 RPA4; replication factor A4 K10742 DNA2; DNA replication ATP-dependent helicase/nuclease Dna2 [EC:5.6.2.3 3.1.-.-] K10743 RNASEH2A; ribonuclease H2 subunit A [EC:3.1.26.4] K10744 RNASEH2B; ribonuclease H2 subunit B K10745 RNASEH2C; ribonuclease H2 subunit C K10747 LIG1; DNA ligase 1 [EC:6.5.1.1 6.5.1.6 6.5.1.7] K10754 RFC1; replication factor C subunit 1 K10755 RFC2_4; replication factor C subunit 2/4 K10756 RFC3_5; replication factor C subunit 3/5 K14159 rnhA-dnaQ; ribonuclease HI / DNA polymerase III subunit epsilon [EC:3.1.26.4 2.7.7.7] K18882 priL, pri2, priB; DNA primase large subunit K22316 rhnA-cobC; ribonuclease H / adenosylcobalamin/alpha-ribazole phosphatase [EC:3.1.26.4 3.1.3.73] 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 ///