DNA damage tolerance by recombination: Molecular pathways and DNA structures.
DNA damage tolerance by recombination: Molecular pathways and DNA structures.
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DOI：
10.1016/j.dnarep.2016.05.008
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发表时间：
2016-08
期刊：
影响因子：
3.8
通讯作者：
Szakal B
中科院分区：
文献类型：
--
作者：
Branzei D;Szakal B
复制扰动会激活 DNA 损伤耐受 (DDT) 途径，这对于促进复制完成和防止叉断裂至关重要，而叉断裂是基因组不稳定的主要原因。 DDT 的一种模式使用跨损伤合成聚合酶，但这也可能引入突变。另一种 DDT 模式涉及重组介导的机制，通常是准确的。 DDT 普遍发生在复制后，但在某些情况下需要同源重组来重新启动分叉。叉反转可以起到稳定停滞叉的作用，但在用于叉重启时也可能导致容易出错的结果。近年来，我们对介导重组介导的损伤旁路的机制和 DNA 结构的理解取得了重要进展，并强调了局部和暂时调节 DDT 途径选择的原则。在这篇综述中，我们总结了重组介导的 DDT 途径及其运作的当前知识和悖论，讨论了中间 DNA 结构如何影响基因组完整性，并概述了未来研究的关键开放问题。
Replication perturbations activate DNA damage tolerance (DDT) pathways, which are crucial to promote replication completion and to prevent fork breakage, a leading cause of genome instability. One mode of DDT uses translesion synthesis polymerases, which however can also introduce mutations. The other DDT mode involves recombination-mediated mechanisms, which are generally accurate. DDT occurs prevalently postreplicatively, but in certain situations homologous recombination is needed to restart forks. Fork reversal can function to stabilize stalled forks, but may also promote error-prone outcome when used for fork restart. Recent years have witnessed important advances in our understanding of the mechanisms and DNA structures that mediate recombination-mediated damage-bypass and highlighted principles that regulate DDT pathway choice locally and temporally. In this review we summarize the current knowledge and paradoxes on recombination-mediated DDT pathways and their workings, discuss how the intermediate DNA structures may influence genome integrity, and outline key open questions for future research.