ORC4/YPR162C Summary Help

Standard Name ORC4 1
Systematic Name YPR162C
Feature Type ORF, Verified
Description Subunit of the origin recognition complex (ORC); ORC directs DNA replication by binding to replication origins and is also involved in transcriptional silencing; ORC4 has a paralog, RIF2, that arose from the whole genome duplication (2, 3 and see Summary Paragraph)
Name Description Origin Recognition Complex 4
Chromosomal Location
ChrXVI:868304 to 866715 | ORF Map | GBrowse
Note: this feature is encoded on the Crick strand.
Gbrowse
Gene Ontology Annotations All ORC4 GO evidence and references
  View Computational GO annotations for ORC4
Molecular Function
Manually curated
Biological Process
Manually curated
Cellular Component
Manually curated
Classical genetics
conditional
reduction of function
Large-scale survey
conditional
null
overexpression
Resources
69 total interaction(s) for 20 unique genes/features.
Physical Interactions
  • Affinity Capture-MS: 43
  • Affinity Capture-RNA: 1
  • Affinity Capture-Western: 5
  • Co-fractionation: 1
  • Co-purification: 2
  • Reconstituted Complex: 5
  • Two-hybrid: 11

Genetic Interactions
  • Dosage Rescue: 1

Resources
Expression Summary
histogram
Resources
Length (a.a.) 529
Molecular Weight (Da) 60,705
Isoelectric Point (pI) 6.78
Localization
Phosphorylation PhosphoGRID | PhosphoPep Database
Structure
Homologs
sequence information
ChrXVI:868304 to 866715 | ORF Map | GBrowse
Note: this feature is encoded on the Crick strand.
SGD ORF map
Last Update Coordinates: 2011-02-03 | Sequence: 1996-07-31
Subfeature details
Relative
Coordinates
Chromosomal
Coordinates
Most Recent Updates
Coordinates Sequence
CDS 1..1590 868304..866715 2011-02-03 1996-07-31
Retrieve sequences
Analyze Sequence
S288C only
S288C vs. other species
S288C vs. other strains
Resources
External Links All Associated Seq | Entrez Gene | Entrez RefSeq Protein | MIPS | Search all NCBI (Entrez) | UniProtKB
Primary SGDIDS000006366
SUMMARY PARAGRAPH for ORC4

The Origin Recognition Complex (ORC) is a six-subunit ATP-dependent DNA-binding protein encoded in yeast by ORC1-6 (5). ORC is a central component for eukaryotic DNA replication, and binds chromatin at replication origins throughout the cell cycle (6). ORC directs DNA replication throughout the genome and is required for its initiation (4, 1, 7). ORC bound at replication origins serves as the foundation for assembly of the pre-replicative complex (pre-RC), which includes Cdc6p, Tah11p (aka Cdt1p), and the Mcm2-7p complex (8, 9, 10). Pre-RC assembly during G1 is required for replication licensing of chromosomes prior to DNA synthesis during S phase (reviewed in 11, 12, and 13). Cell cycle-regulated phosphorylation of Orc2p, Orc6p, Cdc6p, and MCM by the cyclin-dependent protein kinase Cdc28p regulates initiation of DNA replication, including blocking reinitiation in G2/M phase (14, 15, 16, 6).

In yeast, ORC also plays a role in the establishment of silencing at the mating-type loci HML and HMR (4, 1, 7). ORC participates in the assembly of transcriptionally silent chromatin at HML and HMR by recruiting the Sir1p silencing protein to the HML and HMR silencers (17, 18, 7).

Both Orc1p and Orc5p bind ATP, though only Orc1p has ATPase activity (19). The binding of ATP by Orc1p is required for ORC binding to DNA and is essential for cell viability (10). The ATPase activity of Orc1p is involved in formation of the pre-RC (20, 21, 22). ATP binding by Orc5p is crucial for the stability of ORC as a whole. Only the Orc1p-5p subunits are required for origin binding; Orc6p is essential for maintenance of pre-RCs once formed (23). Interactions within ORC suggest that Orc2p-3p-6p may form a core complex (6).

ORC homologs have been found in various eukaryotes, including fission yeast, insects, amphibians, and humans (24).

Last updated: 2007-10-01 Contact SGD

References cited on this page View Complete Literature Guide for ORC4
1) Bell SP, et al.  (1995) The multidomain structure of Orc1p reveals similarity to regulators of DNA replication and transcriptional silencing. Cell 83(4):563-8
2) Bell SP  (2002) The origin recognition complex: from simple origins to complex functions. Genes Dev 16(6):659-72
3) Byrne KP and Wolfe KH  (2005) The Yeast Gene Order Browser: combining curated homology and syntenic context reveals gene fate in polyploid species. Genome Res 15(10):1456-61
4) Bell SP and Stillman B  (1992) ATP-dependent recognition of eukaryotic origins of DNA replication by a multiprotein complex. Nature 357(6374):128-34
5) Chesnokov IN  (2007) Multiple functions of the origin recognition complex. Int Rev Cytol 256():69-109
6) Matsuda K, et al.  (2007) Yeast two-hybrid analysis of the origin recognition complex of Saccharomyces cerevisiae: interaction between subunits and identification of binding proteins. FEMS Yeast Res 7(8):1263-9
7) Gibson DG, et al.  (2006) Cell cycle execution point analysis of ORC function and characterization of the checkpoint response to ORC inactivation in Saccharomyces cerevisiae. Genes Cells 11(6):557-73
8) Rao H and Stillman B  (1995) The origin recognition complex interacts with a bipartite DNA binding site within yeast replicators. Proc Natl Acad Sci U S A 92(6):2224-8
9) Rowley A, et al.  (1995) Initiation complex assembly at budding yeast replication origins begins with the recognition of a bipartite sequence by limiting amounts of the initiator, ORC. EMBO J 14(11):2631-41
10) Speck C, et al.  (2005) ATPase-dependent cooperative binding of ORC and Cdc6 to origin DNA. Nat Struct Mol Biol 12(11):965-71
11) Kelly TJ and Brown GW  (2000) Regulation of chromosome replication. Annu Rev Biochem 69():829-80
12) Bell SP and Dutta A  (2002) DNA replication in eukaryotic cells. Annu Rev Biochem 71():333-74
13) Stillman B  (2005) Origin recognition and the chromosome cycle. FEBS Lett 579(4):877-84
14) Weinreich M, et al.  (2001) Binding of cyclin-dependent kinases to ORC and Cdc6p regulates the chromosome replication cycle. Proc Natl Acad Sci U S A 98(20):11211-7
15) Nguyen VQ, et al.  (2001) Cyclin-dependent kinases prevent DNA re-replication through multiple mechanisms. Nature 411(6841):1068-73
16) Archambault V, et al.  (2005) Disruption of mechanisms that prevent rereplication triggers a DNA damage response. Mol Cell Biol 25(15):6707-21
17) Triolo T and Sternglanz R  (1996) Role of interactions between the origin recognition complex and SIR1 in transcriptional silencing. Nature 381(6579):251-3
18) Fox CA, et al.  (1997) The origin recognition complex, SIR1, and the S phase requirement for silencing. Science 276(5318):1547-51
19) Klemm RD, et al.  (1997) Coordinate binding of ATP and origin DNA regulates the ATPase activity of the origin recognition complex. Cell 88(4):493-502
20) Klemm RD and Bell SP  (2001) ATP bound to the origin recognition complex is important for preRC formation. Proc Natl Acad Sci U S A 98(15):8361-7
21) Bowers JL, et al.  (2004) ATP hydrolysis by ORC catalyzes reiterative Mcm2-7 assembly at a defined origin of replication. Mol Cell 16(6):967-78
22) Randell JC, et al.  (2006) Sequential ATP hydrolysis by Cdc6 and ORC directs loading of the Mcm2-7 helicase. Mol Cell 21(1):29-39
23) Semple JW, et al.  (2006) An essential role for Orc6 in DNA replication through maintenance of pre-replicative complexes. EMBO J 25(21):5150-8
24) Dutta A and Bell SP  (1997) Initiation of DNA replication in eukaryotic cells. Annu Rev Cell Dev Biol 13():293-332