| Description: |
The Origin Recognition Complex (ORC) is a six-subunit ATP-dependent DNA-binding complex encoded in yeast by ORC1-6 []. ORC is a central component for eukaryotic DNA replication, and binds chromatin at replication origins throughout the cell cycle []. ORC directs DNA replication throughout the genome and is required for its initiation [, , ]. 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 [, , ]. Pre-RC assembly during G1 is required for replication licensing of chromosomes prior to DNA synthesis during S phase [, , ]. 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 [, , , ]. 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) [, , ]. 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 [, , ]. Both ORC1 and ORC5 bind ATP, although only ORC1 has ATPase activity []. The binding of ATP by ORC1 is required for ORC binding to DNA and is essential for cell viability []. The ATPase activity of ORC1 is involved in formation of the pre-RC [, , ]. 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 []. Interactions within ORC suggest that ORC2-3-6 may form a core complex []. ORC homologues have been found in various eukaryotes, including fission yeast, insects, amphibians, and humans []. This entry represents subunit 2, which binds the origin of replication. It plays a role in chromosome replication and mating type transcriptional silencing. |
