Reactome: A Curated Pathway Database

Activation of the pre-replicative complex (R-HSA-68962)

Species Homo sapiens


In S. cerevisiae, two ORC subunits, Orc1 and Orc5, both bind ATP, and Orc1 in addition has ATPase activity. Both ATP binding and ATP hydrolysis appear to be essential functions in vivo. ATP binding by Orc1 is unaffected by the association of ORC with origin DNA (ARS) sequences, but ATP hydrolysis is ARS-dependent, being suppressed by associated double-stranded DNA and stimulated by associated single-stranded DNA. These data are consistent with the hypothesis that ORC functions as an ATPase switch, hydrolyzing bound ATP and changing state as DNA unwinds at the origin immediately before replication. It is attractive to speculate that ORC likewise functions as a switch as human pre-replicative complexes are activated, but human Orc proteins are not well enough characterized to allow the model to be critically tested. mRNAs encoding human orthologs of all six Orc proteins have been cloned, and ATP-binding amino acid sequence motifs have been identified in Orc1, Orc4, and Orc5. Interactions among proteins expressed from the cloned genes have been characterized, but the ATP-binding and hydrolyzing properties of these proteins and complexes of them have not been determined.

Locations in the PathwayBrowser
Additional Information
Compartment nucleoplasm
Literature References
pubMedId Title Journal Year
11459976 ATP bound to the origin recognition complex is important for preRC formation. Proc Natl Acad Sci U S A 2001
10801458 ATPase switches controlling DNA replication initiation. Curr Opin Cell Biol 2000
11395502 Architecture of the human origin recognition complex. J Biol Chem 2001
11323433 Assembly of the human origin recognition complex. J Biol Chem 2001
7502077 Conserved initiator proteins in eukaryotes. Science 1996
9038340 Coordinate binding of ATP and origin DNA regulates the ATPase activity of the origin recognition complex. Cell 1997
9353276 Identification of HsORC4, a member of the human origin of replication recognition complex. J Biol Chem 1997
11779870 Nuclear organization of DNA replication initiation proteins in mammalian cells. J Biol Chem 2002
9765232 ORC5L, a new member of the human origin recognition complex, is deleted in uterine leiomyomas and malignant myeloid diseases. J Biol Chem 1998
12169736 Orc6 involved in DNA replication, chromosome segregation, and cytokinesis. Science 2002
10970868 Regulation of origin recognition complex conformation and ATPase activity: differential effects of single-stranded and double-stranded DNA binding. EMBO J 2000
9829972 The Orc4p and Orc5p subunits of the Xenopus and human origin recognition complex are related to Orc1p and Cdc6p. J Biol Chem 1999
10402192 latheo encodes a subunit of the origin recognition complex and disrupts neuronal proliferation and adult olfactory memory when mutant. Neuron 1999