DePamphilis Melvin L
National Institute of Child Health and Human Development, Building 6/416, 9000 Rockville Pike, National Institutes of Health, Bethesda, MD 20892-2753, USA.
Gene. 2003 May 22;310:1-15. doi: 10.1016/s0378-1119(03)00546-8.
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 of these pre-RCs results in bi-directional DNA replication that originates at or close to the ORC DNA binding sites. Recent results have revealed that one or more of the six ORC subunits is modified during the G1 to S-phase transition in such a way that ORC activity is inhibited until mitosis is complete and a nuclear membrane is assembled. In yeast, Cdk1/Clb phosphorylates ORC. In frog eggs, pre-RC assembly destabilizes ORC/chromatin sites, and ORC is eventually hyperphosphorylated and released. In mammals, the affinity of Orc1 for chromatin is selectively reduced during S-phase and restored during early G1-phase. Unbound Orc1 is ubiquitinated during S-phase and in some cases degraded. Thus, most, perhaps all, eukaryotes exhibit some manifestation of an 'ORC cycle' that restricts the ability of ORC to initiate pre-RC assembly to the early G1-phase of the cell cycle, making the 'ORC cycle' the premier step in determining when replication begins.
真核细胞中“起始识别复合物”（ORC）的功能是选择能够组装前复制复合物（pre-RC）的基因组位点。这些pre-RC随后的激活会导致双向DNA复制，其起始于ORC DNA结合位点或其附近。最近的研究结果表明，在G1期到S期的转变过程中，六个ORC亚基中的一个或多个会发生修饰，从而抑制ORC活性，直到有丝分裂完成且核膜组装完成。在酵母中，Cdk1/Clb会使ORC磷酸化。在蛙卵中，pre-RC组装会破坏ORC/染色质位点的稳定性，ORC最终会过度磷酸化并被释放。在哺乳动物中，Orc1与染色质的亲和力在S期会选择性降低，并在G1期早期恢复。未结合的Orc1在S期会被泛素化，在某些情况下会被降解。因此，大多数（也许是所有）真核生物都表现出某种形式的“ORC循环”，该循环将ORC启动pre-RC组装的能力限制在细胞周期的G1期早期，使“ORC循环”成为决定复制何时开始的首要步骤。
