Nature：DNA复制过程的停滞与重启机制

　　

生物通报道，霍华休斯医学研究所，洛克菲勒大学的研究者在DNA复制方面取得新的研究进展，相关成果公布在最新一期的Nature上。

 

DNA复制过程中，当DNA受到损伤是复制叉就停止移动复制过程中止，另外一种情况是复制叉遇到蛋白质-核酸复合物如转录的RNA聚合酶时，复制也中止。比如说，复制颗粒迎头与RNA聚合酶相遇会导致复制叉停滞。然而，复制颗粒与RNA聚合酶相遇仅是暂时终止复制叉的移动，并不影响复制的重新开始。

 

在本研究中，科学家在体外试验中研究复制颗粒与RNA聚合酶相遇时的情况。结果发现，大肠埃希杆菌（Escherichia coli）的复制颗粒将RNA转录物当做上引物，继续复制合成前导链。

 

这些结果表明复制颗粒（一种集聚合与校对活性于一身的多酶复合物）碰到障碍时可以灵活完成自己的任务。RNA聚合酶被从DNA中移走，但复制颗粒和新生成的mRNA仍然附着在其上。一个复制组装因子（beta clamp）会找到mRNA的3\'端，并与仍然结合在一起的复制颗粒相连，后者利用mRNA作为引物重新启动DNA的合成。

 

 

原文摘要：The replisome uses mRNA as a primer after colliding with RNA polymerase

【Abstract】

Replication forks are impeded by DNA damage and protein–nucleic acid complexes such as transcribing RNA polymerase. For example, head-on collision of the replisome with RNA polymerase results in replication fork arrest. However, co-directional collision of the replisome with RNA polymerase has little or no effect on fork progression. Here we examine co-directional collisions between a replisome and RNA polymerase in vitro. We show that the Escherichia coli replisome uses the RNA transcript as a primer to continue leading-strand synthesis after the collision with RNA polymerase that is displaced from the DNA. This action results in a discontinuity in the leading strand, yet the replisome remains intact and bound to DNA during the entire process. These findings underscore the notable plasticity by which the replisome operates to circumvent obstacles in its path and may explain why the leading strand is synthesized discontinuously in vivo.