Dynamics of pre-replication complex proteins during the cell division cycle
Dynamics of pre-replication complex proteins during the cell division cycle
复制标题
DOI：
10.1098/rstb.2003.1360
复制
发表时间：
2004-01-29
影响因子：
6.3
通讯作者：
Stillman, B
中科院分区：
文献类型：
--
作者：
Prasanth, SG;Méndez, J;Stillman, B
每次细胞分裂时复制人类基因组是一个高度协调的过程，确保了遗传信息的准确和高效遗传。保证许多复制来源在每个细胞周期内只激发一次的分子机制一直是密集研究的领域。起源识别复合体(ORC)标志着复制起始点在基因组中的位置，是在起始点组装多蛋白复制前复合体(Pre-RC)的着陆点，由ORC、细胞分裂周期6(CDC6)、依赖于CDC10的转录本(CDT1)和微小染色体维护(MCM)蛋白组成。MCM蛋白是将真核细胞DNA复制限制在每个细胞周期一次的机制的关键参与者，其与染色质的结合标志着前RC形成的最后一步，这一过程被称为“复制许可”。我们提供的数据显示了在G1期，MCM蛋白如何与染色质相关联，可能定义了前RCS，然后预测了细胞周期的S阶段以一种精确协调的方式进行复制分叉运动。DNA复制的过程也必须与其他细胞周期过程仔细协调，包括有丝分裂和胞质分裂。一些控制DNA复制启动的蛋白质可能会与控制这些重要的细胞周期转变的途径相互作用。在这里，我们讨论了人类ORC蛋白参与其他重要功能，以及它们在复制中的真正作用。
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.