
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.
Duke Scholars
Altmetric Attention Stats
Dimensions Citation Stats
Published In
DOI
ISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- Ubiquitin
- S-Phase Kinase-Associated Proteins
- Recombinant Fusion Proteins
- Protein Subunits
- Proteasome Endopeptidase Complex
- Phosphorylation
- Origin Recognition Complex
- Multienzyme Complexes
- Macromolecular Substances
- Humans
Citation

Published In
DOI
ISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- Ubiquitin
- S-Phase Kinase-Associated Proteins
- Recombinant Fusion Proteins
- Protein Subunits
- Proteasome Endopeptidase Complex
- Phosphorylation
- Origin Recognition Complex
- Multienzyme Complexes
- Macromolecular Substances
- Humans