Nascent DNA processing by RecJ favors lesion repair over translesion synthesis at arrested replication forks in Escherichia coli
Nascent DNA processing by RecJ favors lesion repair over translesion synthesis at arrested replication forks in Escherichia coli
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DOI：
10.1073/pnas.0600785103
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发表时间：
2006-06-13
影响因子：
11.1
通讯作者：
Courcelle, Justin
中科院分区：
文献类型：
--
作者：
Courcelle, Charmain T.;Chow, Kin-Hoe;Courcelle, Justin
如果不能准确处理，阻止复制的DNA损伤可能导致重排、突变或致命性。在大肠杆菌中，在UV诱导的DNA损伤后，RecA和几种recF途径蛋白被认为处理被抑制的复制叉，并确保复制准确地恢复。在这里，我们表明，RecJ核酸酶和RecQ解旋酶，部分降解新生的DNA在阻断复制叉，需要快速恢复的DNA合成，并防止潜在的诱变绕过紫外线损伤。在RecJ的情况下，或在较小程度上RecQ，复制的恢复显着延迟，恢复和细胞存活变得依赖于translesion合成聚合酶V的RecJ介导的处理，建议恢复包含损伤的区域的形式，允许修复酶去除阻塞损伤和DNA合成恢复。在没有新生DNA加工的情况下，聚合酶V可以合成通过病变以防止致死，尽管这发生在较慢的动力学和较高的诱变频率下。
DNA lesions that arrest replication can lead to rearrangements, mutations, or lethality when not processed accurately. After UV-induced DNA damage in Escherichia coli, RecA and several recF pathway proteins are thought to process arrested replication forks and ensure that replication resumes accurately. Here, we show that the RecJ nuclease and RecQ helicase, which partially degrade the nascent DNA at blocked replication forks, are required for the rapid recovery of DNA synthesis and prevent the potentially mutagenic bypass of UV lesions. In the absence of RecJ, or to a lesser extent RecQ, the recovery of replication is significantly delayed, and both the recovery and cell survival become dependent on translesion synthesis by polymerase V. The RecJ-mediated processing is proposed to restore the region containing the lesion to a form that allows repair enzymes to remove the blocking lesion and DNA synthesis to resume. In the absence of nascent DNA processing, polymerase V can synthesize past the lesion to prevent lethality, although this occurs with slower kinetics and a higher frequency of mutagenesis.