Replication Termination: Containing Fork Fusion-Mediated Pathologies in Escherichia coli.
Replication Termination: Containing Fork Fusion-Mediated Pathologies in Escherichia coli.
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DOI：
10.3390/genes7080040
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发表时间：
2016-07-25
期刊：
影响因子：
3.5
通讯作者：
Rudolph CJ
中科院分区：
文献类型：
--
作者：
Dimude JU;Midgley-Smith SL;Stein M;Rudolph CJ
细菌染色体的复制是通过两个复制叉在一个确定的起点组装而开始的。分叉双向进行，直到它们在原点对面的专门终止区域融合。这个区域的两侧是极性复制叉暂停位点，允许叉进入但不能离开。这种复制叉陷阱的确切功能仍然是个谜，因为没有明显的表型与其失活有关。然而，如果第二叉在一个障碍物上停滞，那么叉陷阱就会成为细胞的一个严重问题，因为复制无法完成，这表明维持这种染色体排列的重要进化优势必须存在。最近，我们证明了复制叉的迎头融合可以触发染色体的过度复制。这种过度复制通常被许多蛋白质包括RecG解旋酶和3'核酸外切酶阻止。然而，即使在没有这些蛋白质的情况下，它也可以安全地包含在复制叉陷阱中，这突出表明多个系统可能参与协调复制叉融合。在这里，我们讨论是否考虑与头上的复制叉融合事件相关的问题，帮助我们更好地了解复制叉陷阱在细胞代谢中的重要作用。
Duplication of bacterial chromosomes is initiated via the assembly of two replication forks at a single defined origin. Forks proceed bi-directionally until they fuse in a specialised termination area opposite the origin. This area is flanked by polar replication fork pause sites that allow forks to enter but not to leave. The precise function of this replication fork trap has remained enigmatic, as no obvious phenotypes have been associated with its inactivation. However, the fork trap becomes a serious problem to cells if the second fork is stalled at an impediment, as replication cannot be completed, suggesting that a significant evolutionary advantage for maintaining this chromosomal arrangement must exist. Recently, we demonstrated that head-on fusion of replication forks can trigger over-replication of the chromosome. This over-replication is normally prevented by a number of proteins including RecG helicase and 3’ exonucleases. However, even in the absence of these proteins it can be safely contained within the replication fork trap, highlighting that multiple systems might be involved in coordinating replication fork fusions. Here, we discuss whether considering the problems associated with head-on replication fork fusion events helps us to better understand the important role of the replication fork trap in cellular metabolism.