Direct observation of stalled fork restart via fork regression in the T4 replication system.

Direct observation of stalled fork restart via fork regression in the T4 replication system.
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DOI:
10.1126/science.1225437
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发表时间:
2012-11-30
期刊:
Science (New York, N.Y.)
影响因子:
--
通讯作者:
Benkovic SJ
Benkovic SJ
中科院分区:
其他
文献类型:
--
作者:
Manosas M;Perumal SK;Croquette V;Benkovic SJ

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停滞的复制叉的重新启动是 DNA 复制的主要挑战。根据损坏的性质,可能会触发不同的修复过程;一种是模板切换,即通过叉回归绕过前导链损伤。利用磁力镊子研究T4噬菌体酶,我们在体外重现了模板转换的完整过程。我们表明,UvsW DNA 解旋酶与 T4 全酶配合,可以通过周期性形成和迁移四向霍利迪连接体的伪随机过程来克服前导链损伤损伤。修复过程的启动需要通过复制解旋酶的离开来部分复制体分解。结果支持叉回归途径在 DNA 修复中的作用。
The restart of a stalled replication fork is a major challenge for DNA replication. Depending upon the nature of the damage, different repair processes might be triggered; one is template switching that is bypass of a leading strand lesion via fork regression. Using magnetic tweezers to study the T4 bacteriophage enzymes, we have reproduced in vitro the complete process of template switching. We show that the UvsW DNA helicase in cooperation with the T4 holoenzyme can overcome leading strand lesion damage by a pseudo stochastic process periodically forming and migrating a four ways Holliday junction. The initiation of the repair process requires partial replisome disassembly via the departure of the replicative helicase. The results support the role of fork regression pathways in DNA repair.
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