|Depamphilis, M. - NIH|
Submitted to: Biochemistry and Molecular Biology Abstracts
Publication Type: Abstract Only
Publication Acceptance Date: April 3, 2003
Publication Date: N/A
Technical Abstract: The initiation of DNA replication in mammalian cells is a cell cycle-regulated process requiring the assembly of a pre-replication complex at origins of DNA replication during G1 phase. Recent results strongly suggest the "origin recognition complex" (ORC) determines where and when replication begins by limiting new initiation events to once-per-origin-per-cell division. While in both fission and budding yeast ORC remains stably bound to chromatin throughout the cell cycle, in mammals, Orc1 is selectively released from chromatin during S-phase, ubiquitinated, in some cases degraded, and then rebound to chromatin during the M to G1 transition where it initiates assembly of a pre-replication complex. Moreover, new evidence now suggests that protein kinase activity and phosphorylation of Orc1 are also involved in the regulation of the "ORC" function during the cell cycle. Cdc2/cdk1 was found tightly associated with Orc during the metaphase of the cell cycle, therefore prevent Orc1 from binding of chromatin. Thus, there exists in multicellular animals an 'ORC cycle" that prevents reinitiation of DNA replication until mitosis is complete and a nuclear membrane is assembled. We suggest that the first step in regulation cell division occurs when a functional ORC is assembled at specific DNA sites along the eukaryotic genome.