North West Cancer Research Fund Institute, College of Natural Sciences, Bangor University, Bangor, Gwynedd, UK.
Cell Cycle. 2010 Feb 15;9(4):700-5. doi: 10.4161/cc.9.4.10676. Epub 2010 Feb 17.
Failures in DNA replication are a potent force for driving genome instability. The proteins which form the replisome, the DNA replication machinery, play a fundamental role in preventing replicative catastrophes. The Tim (TIMELESS/TIMEOUT) and Tipin proteins are two conserved replisome associated proteins which have functions in preventing replication fork collapse and replicative checkpoint signalling in response to factors which slow the progression of the replisome. Intriguingly, TIMELESS family members have been implicated in the regulation of the biological clock, giving a tantalising pointer to a possible link between DNA replication and circadian rhythm control. Here we report on our current understanding of the many facets of these protein families in maintaining genome stability and replication checkpoint control.
DNA 复制失败是导致基因组不稳定的强大力量。形成复制体（DNA 复制机制）的蛋白质在防止复制灾难方面发挥着至关重要的作用。Tim（TIMELSS/TIMEOUT）和 Tipin 蛋白是两种保守的复制体相关蛋白，它们在防止复制叉崩溃和复制检查点信号转导方面具有功能，以响应减缓复制体进程的因素。有趣的是，TIMES 家族成员与生物钟的调节有关，这为 DNA 复制和昼夜节律控制之间可能存在联系提供了一个诱人的线索。在这里，我们报告了我们目前对这些蛋白质家族在维持基因组稳定性和复制检查点控制方面的许多方面的理解。
