Prasanth Supriya G, Méndez Juan, Prasanth Kannanganattu V, Stillman Bruce
Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, NY 11724, USA.
Philos Trans R Soc Lond B Biol Sci. 2004 Jan 29;359(1441):7-16. doi: 10.1098/rstb.2003.1360.
Replication of the human genome every time a cell divides is a highly coordinated process that ensures accurate and efficient inheritance of the genetic information. The molecular mechanism that guarantees that many origins of replication fire only once per cell-cycle has been the area of intense research. The origin recognition complex (ORC) marks the position of replication origins in the genome and serves as the landing pad for the assembly of a multiprotein, pre-replicative complex (pre-RC) at the origins, consisting of ORC, cell division cycle 6 (Cdc6), Cdc10-dependent transcript (Cdt1) and mini-chromosome maintenance (MCM) proteins. The MCM proteins serve as key participants in the mechanism that limits eukaryotic DNA replication to once-per-cell-cycle and its binding to the chromatin marks the final step of pre-RC formation, a process referred to as 'replication licensing'. We present data demonstrating how the MCM proteins associate with the chromatin during the G1 phase, probably defining pre-RCs and then anticipate replication fork movement in a precisely coordinated manner during the S phase of the cell cycle. The process of DNA replication must also be carefully coordinated with other cell-cycle processes including mitosis and cytokinesis. Some of the proteins that control initiation of DNA replication are likely to interact with the pathways that control these important cell-cycle transitions. Herein, we discuss the participation of human ORC proteins in other vital functions, in addition to their bona fide roles in replication.
每次细胞分裂时人类基因组的复制是一个高度协调的过程，可确保遗传信息的准确和有效遗传。保证许多复制起点在每个细胞周期仅启动一次的分子机制一直是深入研究的领域。起始识别复合物（ORC）标记基因组中复制起点的位置，并作为在起点组装多蛋白前复制复合物（pre-RC）的着陆平台，该复合物由ORC、细胞分裂周期6（Cdc6）、Cdc10依赖性转录物（Cdt1）和微小染色体维持（MCM）蛋白组成。MCM蛋白是将真核生物DNA复制限制在每个细胞周期一次的机制中的关键参与者，其与染色质的结合标志着pre-RC形成的最后一步，这一过程称为“复制许可”。我们提供的数据表明MCM蛋白在G1期如何与染色质结合，可能确定pre-RC，然后在细胞周期的S期以精确协调的方式预测复制叉的移动。DNA复制过程还必须与包括有丝分裂和胞质分裂在内的其他细胞周期过程仔细协调。一些控制DNA复制起始的蛋白质可能与控制这些重要细胞周期转变的途径相互作用。在此，我们讨论人类ORC蛋白除了在复制中的真正作用外，在其他重要功能中的参与情况。
