Human origin recognition complex large subunit is degraded by ubiquitin-mediated proteolysis after initiation of DNA replication.
Eukaryotic cells possess overlapping mechanisms to ensure that DNA replication is restricted to the S phase of the cell cycle. The levels of hOrc1p, the largest subunit of the human origin recognition complex, vary during the cell division cycle. In rapidly proliferating cells, hOrc1p is expressed and targeted to chromatin as cells exit mitosis and prereplicative complexes are formed. Later, as cyclin A accumulates and cells enter S phase, hOrc1p is ubiquitinated on chromatin and then degraded. hOrc1p destruction occurs through the proteasome and is signaled in part by the SCF(Skp2) ubiquitin-ligase complex. Other hORC subunits are stable throughout the cell cycle. The regulation of hOrc1p may be an important mechanism in maintaining the ploidy in human cells.
Méndez
Juan
J
Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA.
Zou-Yang
X Helena
XH
Kim
So-Young
SY
Hidaka
Masumi
M
Tansey
William P
WP
Stillman
Bruce
B
D000818:Animals; D002453:Cell Cycle / Q000502:physiology*; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D002458:Cell Fractionation; D002843:Chromatin / Q000378:metabolism*; D019925:Cyclin A / Q000378:metabolism; D003546:Cysteine Endopeptidases / Q000378:metabolism; D004249:DNA Damage; D004261:DNA Replication / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005434:Flow Cytometry; D020868:Gene Silencing; D006367:HeLa Cells; D006801:Humans; D046911:Macromolecular Substances; D009097:Multienzyme Complexes / Q000378:metabolism; D051738:Origin Recognition Complex; D010766:Phosphorylation; D046988:Proteasome Endopeptidase Complex; D021122:Protein Subunits; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D044786:S-Phase Kinase-Associated Proteins; D025801:Ubiquitin / Q000378:metabolism*
D018797:Cell Cycle Proteins; D002843:Chromatin; D019925:Cyclin A; D004268:DNA-Binding Proteins; D046911:Macromolecular Substances; D009097:Multienzyme Complexes; C497223:ORC1 protein, human; D051738:Origin Recognition Complex; D021122:Protein Subunits; D011993:Recombinant Fusion Proteins; D044786:S-Phase Kinase-Associated Proteins; D025801:Ubiquitin; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex