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Activation of the pre-replicative complex

Summary

Organism

Homo sapiens (human)

Reactome

R-HSA-68962

PubChem

R-HSA-68962

Description

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.

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SPV: a JavaScript Signaling Pathway Visualizer, Bioinformatics, 2018

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UniProt ID	Protein Name	Gene Symbol	Pathway Viewer
O00311	Cell division cycle 7-related protein kinase	CDC7 CDC7L1	view
O43913	Origin recognition complex subunit 5	ORC5 ORC5L	view
O75496	Geminin	GMNN	view
P09884	DNA polymerase alpha catalytic subunit	POLA POLA1	view
P15927	Replication protein A 32 kDa subunit	REPA2 RPA2 RPA32 RPA34	view
P25205	DNA replication licensing factor MCM3	MCM3	view
P27694	Replication protein A 70 kDa DNA-binding subunit	REPA1 RPA1 RPA70	view
P33991	DNA replication licensing factor MCM4	CDC21 MCM4	view
P33993	DNA replication licensing factor MCM7	CDC47 MCM2 MCM7	view
P49736	DNA replication licensing factor MCM2	BM28 CCNL1 CDCL1 KIAA0030 MCM2	view

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