The 'ORC cycle': a novel pathway for regulating eukaryotic DNA replication.

摘要: The function of the ‘origin recognition complex’ (ORC) in eukaryotic cells is to select genomic sites where pre-replication complexes (pre-RCs) can be assembled. Subsequent activation these pre-RCs results bi-directional DNA replication that originates at or close ORC binding sites. Recent have revealed one more six subunits modified during G1 S-phase transition such a way activity inhibited until mitosis complete and nuclear membrane In yeast, Cdk1/Clb phosphorylates ORC. frog eggs, pre-RC assembly destabilizes ORC/chromatin sites, eventually hyperphosphorylated released. mammals, affinity Orc1 for chromatin selectively reduced restored early G1-phase. Unbound ubiquitinated some cases degraded. Thus, most, perhaps all, eukaryotes exhibit manifestation an ‘ORC cycle’ restricts ability initiate G1-phase cell cycle, making premier step determining when begins. q 2003 Published by Elsevier Science B.V.