S-phase checkpoint proteins Tof1 and Mrc1 form a stable replication-pausing complex
S-phase checkpoint proteins Tof1 and Mrc1 form a stable replication-pausing complex
复制标题
DOI：
10.1038/nature01900
复制
发表时间：
2003-08-28
期刊：
影响因子：
64.8
通讯作者：
Shirahige, K
中科院分区：
文献类型：
--
作者：
Katou, Y;Kanoh, Y;Shirahige, K
检查点调节机制在维持基因组的完整性方面具有重要作用（1-5）。这在细胞周期的S期尤其重要，此时基因组DNA最容易受到各种环境危害的影响（3，6，7）。当化学试剂损伤DNA时，检查点信号通路的激活导致DNA复制的暂时停止。一个复制暂停复合物被认为是在被逮捕的叉子，以激活进一步的检查点级联，导致修复受损的DNA。因此，检查点因子被认为不仅可以阻止复制，而且可以在复制叉处维持稳定的复制复合物（6-9）。然而，耦合检查点调节和复制停滞的分子机制是未知的。在这里，我们证明了检查点调节蛋白Tof 1和Mrc 1直接与酿酒酵母中的DNA复制机制相互作用。当羟基脲阻断染色体复制时，这种组装形成稳定的暂停结构，其用于锚随后的DNA修复事件。
The checkpoint regulatory mechanism has an important role in maintaining the integrity of the genome(1-5). This is particularly important in S phase of the cell cycle, when genomic DNA is most susceptible to various environmental hazards(3,6,7). When chemical agents damage DNA, activation of checkpoint signalling pathways results in a temporary cessation of DNA replication. A replication-pausing complex is believed to be created at the arrested forks to activate further checkpoint cascades, leading to repair of the damaged DNA. Thus, checkpoint factors are thought to act not only to arrest replication but also to maintain a stable replication complex at replication forks(6-9). However, the molecular mechanism coupling checkpoint regulation and replication arrest is unknown. Here we demonstrate that the checkpoint regulatory proteins Tof1 and Mrc1 interact directly with the DNA replication machinery in Saccharomyces cerevisiae. When hydroxyurea blocks chromosomal replication, this assembly forms a stable pausing structure that serves to anchor subsequent DNA repair events.