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Role for Cdk1 (Cdc2)/Cyclin A in Preventing the Mammalian Origin Recognition Complex's Largest Subunit (Orc1) from Binding to Chromatin during Mitosis.

Authors :
Cong-jun Li
Vassilev, Alex
DePamphilis, Melvin L.
Source :
Molecular & Cellular Biology. Jul2004, Vol. 24 Issue 13, p5875-5886. 12p. 1 Diagram, 21 Graphs.
Publication Year :
2004

Abstract

The eukaryotic origin recognition complex (ORC) selects the genomic sites where prereplication complexes are assembled and DNA replication begins. In proliferating mammalian cells, ORC activity appears to be regulated by reducing the affinity of the Orc1 subunit for chromatin during S phase and then preventing reformation of a stable ORC-chromatin complex until mitosis is completed and a nuclear membrane is assembled. Here we show that part of the mechanism by which this is accomplished is the selective association of Orcl with Cdk1 (Cdc2)/cyclin A during the G2/M phase of cell division. This association accounted for the appearance in M-phase cells of hyperphosphorylated Orc1 that was subsequently dephosphorylated during the M-to-G1 transition. Moreover, inhibition of Cdk activity in metaphase cells resulted in rapid binding of Orc1 to chromatin. However, chromatin binding was not mediated through increased affinity of Orc1 for Orc2, suggesting that additional events are involved in the assembly of functional ORC-chromatin sites. These results reveal that the same cyclin-dependent protein kinase that initiates mitosis in mammalian cells also concomitantly inhibits assembly of functional ORC-chromatin sites. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
02707306
Volume :
24
Issue :
13
Database :
Academic Search Index
Journal :
Molecular & Cellular Biology
Publication Type :
Academic Journal
Accession number :
14602022
Full Text :
https://doi.org/10.1128/MCB.24.13.5875-5886.2004