InterPro domain: IPR041664

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 [ 1 ]. ORC is a central component for eukaryotic DNA replication, and binds chromatin at replication origins throughout the cell cycle [ 2 ]. ORC directs DNA replication throughout the genome and is required for its initiation [ 3 , 4 , 5 ]. 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 [ 6 , 7 , 8 ]. Pre-RC assembly during G1 is required for replication licensing of chromosomes prior to DNA synthesis during S phase [ 9 , 10 , 11 ]. 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 [ 12 , 12 , 13 , 14 ].

Both ORC1 and ORC5 bind ATP, although only ORC1 has ATPase activity [ 15 ]. The binding of ATP by ORC1 is required for ORC binding to DNA and is essential for cell viability [ 16 ]. The ATPase activity of ORC1 is involved in formation of the pre-RC [ 16 , 17 , 18 ]. 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 [ 19 ]. Interactions within ORC suggest that ORC2-3-6 may form a core complex [ 20 ].

1. Multiple functions of the origin recognition complex. Int. Rev. Cytol. 256, 69-109
2. Yeast two-hybrid analysis of the origin recognition complex of Saccharomyces cerevisiae: interaction between subunits and identification of binding proteins. FEMS Yeast Res. 7, 1263-9
3. ATP-dependent recognition of eukaryotic origins of DNA replication by a multiprotein complex. Nature 357, 128-34
4. The multidomain structure of Orc1p reveals similarity to regulators of DNA replication and transcriptional silencing. Cell 83, 563-8
5. Cell cycle execution point analysis of ORC function and characterization of the checkpoint response to ORC inactivation in Saccharomyces cerevisiae. Genes Cells 11, 557-73
6. The origin recognition complex interacts with a bipartite DNA binding site within yeast replicators. Proc. Natl. Acad. Sci. U.S.A. 92, 2224-8
7. 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, 2631-41
8. ATPase-dependent cooperative binding of ORC and Cdc6 to origin DNA. Nat. Struct. Mol. Biol. 12, 965-71
9. Regulation of chromosome replication. Annu. Rev. Biochem. 69, 829-80
10. DNA replication in eukaryotic cells. Annu. Rev. Biochem. 71, 333-74
11. Origin recognition and the chromosome cycle. FEBS Lett. 579, 877-84
12. Binding of cyclin-dependent kinases to ORC and Cdc6p regulates the chromosome replication cycle. Proc. Natl. Acad. Sci. U.S.A. 98, 11211-7
13. Cyclin-dependent kinases prevent DNA re-replication through multiple mechanisms. Nature 411, 1068-73
14. Disruption of mechanisms that prevent rereplication triggers a DNA damage response. Mol. Cell. Biol. 25, 6707-21
15. Coordinate binding of ATP and origin DNA regulates the ATPase activity of the origin recognition complex. Cell 88, 493-502
16. ATP bound to the origin recognition complex is important for preRC formation. Proc. Natl. Acad. Sci. U.S.A. 98, 8361-7
17. ATP hydrolysis by ORC catalyzes reiterative Mcm2-7 assembly at a defined origin of replication. Mol. Cell 16, 967-78
18. Sequential ATP hydrolysis by Cdc6 and ORC directs loading of the Mcm2-7 helicase. Mol. Cell 21, 29-39
19. An essential role for Orc6 in DNA replication through maintenance of pre-replicative complexes. EMBO J. 25, 5150-8