The lesion bypass pathway, translesion synthesis (TLS), exists in essentially all organisms and is considered a pathway for postreplicative gap repair and, at the same time, for lesion tolerance. As with the saying “a trip is not over until you get back home,” studying TLS only at the site of the lesion is not enough to understand the whole process of TLS. Recently, a genetic study uncovered that polymerase V (Pol V), a poorly expressed Escherichia coli TLS polymerase, is not only involved in the TLS step per se but also participates in the gap-filling reaction over several hundred nucleotides. The same study revealed that in contrast, Pol IV, another highly expressed TLS polymerase, essentially stays away from the gap-filling reaction. These observations imply fundamentally different ways these polymerases are recruited to DNA in cells. While access of Pol IV appears to be governed by mass action, efficient recruitment of Pol V involves a chaperone-like action of the RecA filament. We present a model of Pol V activation: the 3′ tip of the RecA filament initially stabilizes Pol V to allow stable complex formation with a sliding β-clamp, followed by the capture of the terminal RecA monomer by Pol V, thus forming a functional Pol V complex. This activation process likely determines higher accessibility of Pol V than of Pol IV to normal DNA. Finally, we discuss the biological significance of TLS polymerases during gap-filling reactions: error-prone gap-filling synthesis may contribute as a driving force for genetic diversity, adaptive mutation, and evolution.

中文翻译：

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大肠杆菌中跨病变合成的综合观点。

病变旁路途径，即病变合成（TLS），基本上存在于所有生物中，被认为是复制后间隙修复的途径，同时也是病变耐受性的途径。就像“旅行直到您回到家还没有结束”这样的说法一样，仅在病变部位研究TLS不足以了解TLS的整个过程。最近，基因研究揭示，聚合酶V（波尔V），一个不善表达大肠杆菌TLS聚合酶，不仅参与TLS步骤本身而且还参与了数百个核苷酸的缺口填充反应。相同的研究表明，相比之下，另一种高度表达的TLS聚合酶Pol IV基本上远离缺口填充反应。这些观察结果暗示了这些聚合酶在细胞中募集到DNA的根本不同方式。尽管Pol IV的进入似乎受大规模行动支配，但Pol V的有效募集涉及RecA细丝的分子伴侣样作用。我们提出了Pol V激活的模型：RecA细丝的3'末端最初使Pol V稳定，以使稳定的复合物与滑动的β钳一起形成，然后由Pol V捕获末端RecA单体，从而形成功能性Pol V复合体。与正常DNA相比，这种激活过程可能决定了Pol V比Pol IV更高的可及性。最后，