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 the largest subunit of the origin recognition complex, subunit 1, which directs DNA replication by binding to replication origins and is also involved in transcriptional silencing; exhibits ATPase activity [, ]. Sir3 is the homologue in Saccharomyces cerevisiae [].
This entry represents the ORC1-binding domain of Sir1. It has a complex fold, composed of an alpha hairpin, meander β-sheet and a five-stranded barrel of unusual topology. Sir1 interacts with the BAH domain of the Orc1 subunit of the origin recognition complex (ORC) resulting in the establishment of silent chromatin at HMR and HML in S.cerevisiae []. The amino acids from the ORC interaction region of Sir1 are presented on a conserved, convex surface that forms a complementary interface with the Orc1 BAH domain, critical for transcriptional silencing [].
This entry represents the ORC-binding domain of Sir1. Sir1 interacts with the BAH domain of the Orc1 subunit of the origin recognition complex (ORC) resulting in the establishment of silent chromatin at HMR and HML in S.cerevisiae []. The amino acids from the ORC interaction region of Sir1 are presented on a conserved, convex surface that forms a complementary interface with the Orc1 BAH domain, critical for transcriptional silencing []. Proteins containing this domain also include Y' element ATP-dependent helicase protein 1, which catalyses DNA unwinding and is involved in telomerase-independent telomere maintenance [].
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 group represents an origin recognition complex, subunit 4.
This domain contains a P-loop motif that is characteristic of the AAA superfamily. This domain has been classified as AAA_16 in Pfam and can be found in the Origin Recognition Complex (ORC) subunits and serine/threonine-protein kinase PknK. 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 (akaCdt1), 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 [, , , ].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 [].
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.
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 [].
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 [].
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 the C terminus of origin recognition complex subunit 4 [, ].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 [].
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 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 [, ]. In Saccharomyces cerevisiae (Baker's yeast), both ends of the Orc6 interact with Cdt1 []and the N terminus mediates an interaction with the S-phase cyclin Clb5 [].
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 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 [, ]. In Saccharomyces cerevisiae (Baker's yeast), both ends of the Orc6 interact with Cdt1 []and the N terminus mediates an interaction with the S-phase cyclin Clb5 [].
Cdc6 (also known as Cell division cycle 6 or Cdc18) functions as a regulator at the early stages of DNA replication, by helping to recruit and load the Minichromosome Maintenance Complex (MCM) onto DNA and may have additional roles in the control of mitotic entry. Precise duplication of chromosomal DNA is required for genomic stability during replication. Cdc6 has an essential role in DNA replication and irregular expression of Cdc6 may lead to genomic instability. Cdc6 over-expression is observed in many cancerous lesions. DNA replication begins when an origin recognition complex (ORC) binds to a replication origin site on the chromatin. Studies indicate that Cdc6 interacts with ORC through the Orc1 subunit, and that this association increases the specificity of the ORC-origins interaction. Further studies suggest that hydrolysis of Cdc6-bound ATP promotes the association of the replication licensing factor Cdt1 with origins through an interaction with Orc6 and this in turn promotes the loading of MCM2-7 helicase onto chromatin. The MCM2-7 complex promotes the unwinding of DNA origins, and the binding of additional factors to initiate the DNA replication. S-Cdk (S-phase cyclin and cyclin-dependent kinase complex) prevents rereplication by causing the Cdc6 protein to dissociate from ORC and prevents the Cdc6 and MCM proteins from reassembling at any origin. By phosphorylating Cdc6, S-Cdk also triggers Cdc6's ubiquitination. The Cdc6 protein is composed of three domains, an N-terminal AAA+ domain with Walker A and B, and Sensor-1 and -2 motifs. The central region contains a conserved nucleotide binding/ATPase domain and is a member of the ATPase superfamily. [, , , , ].The C-terminal domain of cell division control protein 6 (CDC6) assumes a winged helix fold, with a five α-helical bundle (α15-α19) structure, backed on one side by three beta strands (β6-β8). It has been shown that this domain acts as a DNA-localisation factor, however its exact function is, as yet, unknown. Putative functions include: (1) mediation of protein-protein interactions and (2) regulation of nucleotide binding and hydrolysis. Mutagenesis studies have shown that this domain is essential for appropriate CDC6 activity [].
