Human origin recognition complex large subunit is degraded by ubiquitin-mediated proteolysis after initiation of DNA replication.

Méndez J, Zou-Yang XH, Kim SY, Hidaka M, Tansey WP, Stillman B
Mol Cell. 2002 9 (3): 481-91

PMID: 11931757 · DOI:10.1016/s1097-2765(02)00467-7

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.

MeSH Terms (23)

Animals Cell Cycle Cell Cycle Proteins Cell Fractionation Chromatin Cyclin A Cysteine Endopeptidases DNA-Binding Proteins DNA Damage DNA Replication Flow Cytometry Gene Silencing HeLa Cells Humans Macromolecular Substances Multienzyme Complexes Origin Recognition Complex Phosphorylation Proteasome Endopeptidase Complex Protein Subunits Recombinant Fusion Proteins S-Phase Kinase-Associated Proteins Ubiquitin

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