Pathways & interactions
Origin recognition complex, subunit 6 (IPR008721)
Short name: ORC6
- Origin recognition complex, subunit 6 (IPR008721)
- Origin recognition complex, subunit 6, fungi (IPR016811)
- Origin recognition complex, subunit 6, metazoa/plant (IPR020529)
The Origin Recognition Complex (ORC) is a six-subunit ATP-dependent DNA-binding complex encoded in yeast by ORC1-6 [PMID: 17241905]. ORC is a central component for eukaryotic DNA replication, and binds chromatin at replication origins throughout the cell cycle [PMID: 17825065]. ORC directs DNA replication throughout the genome and is required for its initiation [PMID: 1579162, PMID: 7585959, PMID: 16716188]. ORC bound at replication origins serves as the foundation for assembly of the pre-replicative complex (pre-RC), which includes Cdc6, Tah11 (aka Cdt1), and the Mcm2-7 complex [PMID: 7892251, PMID: 7781615, PMID: 16228006]. Pre-RC assembly during G1 is required for replication licensing of chromosomes prior to DNA synthesis during S phase [PMID: 10966477, PMID: 12045100, PMID: 15680967]. Cell cycle-regulated phosphorylation of ORC2, ORC6, Cdc6, and MCM by the cyclin-dependent protein kinase Cdc28 regulates initiation of DNA replication, including blocking reinitiation in G2/M phase [PMID: 17825065, PMID: 11572976, PMID: 11429609, PMID: 16024805].
In yeast, ORC also plays a role in the establishment of silencing at the mating-type loci Hidden MAT Left (HML) and Hidden MAT Right (HMR) [PMID: 1579162, PMID: 7585959, PMID: 16716188]. ORC participates in the assembly of transcriptionally silent chromatin at HML and HMR by recruiting the Sir1 silencing protein to the HML and HMR silencers [PMID: 16716188, PMID: 8622770, PMID: 9171055].
Both ORC1 and ORC5 bind ATP, although only ORC1 has ATPase activity [PMID: 9038340]. The binding of ATP by ORC1 is required for ORC binding to DNA and is essential for cell viability [PMID: 16228006]. The ATPase activity of ORC1 is involved in formation of the pre-RC [PMID: 11459976, PMID: 15610739, PMID: 16387651]. ATP binding by ORC5 is crucial for the stability of ORC as a whole. Only the ORC1-5 subunits are required for origin binding; ORC6 is essential for maintenance of pre-RCs once formed [PMID: 17053779]. Interactions within ORC suggest that ORC2-3-6 may form a core complex [PMID: 17825065].
ORC homologues have been found in various eukaryotes, including fission yeast, insects, amphibians, and humans [PMID: 9442876].
This entry represents subunit 6, which directs DNA replication by binding to replication origins and is also involved in transcriptional silencing; interacts with Spp1 and with trimethylated histone H3; phosphorylated by Cdc28 [PMID: 11914271, PMID: 14574415].
- PF05460 (ORC6)