How to fix DNA-protein crosslinks.

How to fix DNA-protein crosslinks.
复制标题

如何修复DNA-蛋白质交联。

DOI:
10.1016/j.dnarep.2020.102924
复制
发表时间:
2020-10
期刊:
影响因子:
3.8
通讯作者:
Duxin JP
Duxin JP
中科院分区:
医学3区
文献类型:
--
作者:
Kühbacher U;Duxin JP

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作用于 DNA 或与其非常接近的蛋白质可能会无意中与 DNA 交联并形成剧毒损伤,称为 DNA-蛋白质交联 (DPC)。 DPC 是由不同的化疗药物、环境或内源性交联剂产生的,或者是由 DNA 损伤导致某些 DNA 加工酶的催化循环停滞而产生的。这些庞大的加合物会损害 DNA 复制或转录等 DNA 过程,因此对基因组完整性构成严重威胁。 DPC 的巨大多样性表明修复它们的规范机制不只一种。事实上,许多不同的酶已被证明可以通过处理蛋白质、DNA 或交联本身来作用于 DPC。此外,细胞周期阶段或细胞类型可能决定途径选择。近年来,对 S 期 DPC 修复的详细了解已经开始出现。在这里,我们回顾了当前关于复制耦合 DPC 修复机制的知识,并描述并推测了去除 S 期之外的 DPC 的可能途径。此外,我们强调了最近的范式转变发现,该发现表明 DPC 并不总是有害的,但也可以发挥保护作用,保护基因组免受更有害形式的 DNA 损伤。
Proteins that act on DNA, or are in close proximity to it, can become inadvertently crosslinked to DNA and form highly toxic lesions, known as DNA-protein crosslinks (DPCs). DPCs are generated by different chemotherapeutics, environmental or endogenous sources of crosslinking agents, or by lesions on DNA that stall the catalytic cycle of certain DNA processing enzymes. These bulky adducts impair processes on DNA such as DNA replication or transcription, and therefore pose a serious threat to genome integrity. The large diversity of DPCs suggests that there is more than one canonical mechanism to repair them. Indeed, many different enzymes have been shown to act on DPCs by either processing the protein, the DNA or the crosslink itself. In addition, the cell cycle stage or cell type are likely to dictate pathway choice. In recent years, a detailed understanding of DPC repair during S phase has started to emerge. Here, we review the current knowledge on the mechanisms of replication-coupled DPC repair, and describe and also speculate on possible pathways that remove DPCs outside of S phase. Moreover, we highlight a recent paradigm shifting finding that indicates that DPCs are not always detrimental, but can also play a protective role, preserving the genome from more deleterious forms of DNA damage.
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