ADP-ribosylation of DNA and RNA.
ADP-ribosylation of DNA and RNA.
复制标题
DNA和RNA的ADP核糖基化。
DOI：
10.1016/j.dnarep.2021.103144
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发表时间：
2021-09
期刊：
影响因子：
3.8
通讯作者：
Ahel I
中科院分区：
文献类型：
--
作者：
Groslambert J;Prokhorova E;Ahel I
ADP-核糖化是一种大分子的化学修饰，存在于生命的所有领域，并已知调节各种细胞过程。值得注意的是，它在DNA损伤反应中具有公认的作用。虽然它在历史上被认为是蛋白质的翻译后修饰，但最近的研究表明，核酸也可以作为可逆的ADP-核糖化的底物。更准确地说，DNA碱基、磷酸化DNA末端和磷酸化RNA末端的ADP-核糖化已有报道。我们将详细讨论这三种类型的修改。在包括结核分枝杆菌在内的多种细菌中，胸苷的ADP-核糖基化已成为一种名为DarTG的毒素-抗毒素系统的作用方式，其结果被细胞视为DNA损伤。另一方面，哺乳动物DNA损伤传感器PARP1、PARP2和PARP3在体外被证明能够使双链DNA的ADP-核糖化末端磷酸化。此外，TRPT1和包括PARP10在内的几种PARP酶在体外可以将ADP-核糖添加到单链RNA的5‘-磷酸化末端，这代表了一种新的RNA封顶机制。总之，这些发现导致了一个新的令人兴奋的研究领域的出现，即DNA和RNA ADP-核糖化，这可能对DNA修复、复制和表观遗传学领域产生深远的影响。
ADP-ribosylation is a chemical modification of macromolecules found across all domains of life and known to regulate a variety of cellular processes. Notably, it has a well-established role in the DNA damage response. While it was historically known as a post-translational modification of proteins, recent studies have shown that nucleic acids can also serve as substrates of reversible ADP-ribosylation. More precisely, ADP-ribosylation of DNA bases, phosphorylated DNA ends and phosphorylated RNA ends have been reported. We will discuss these three types of modification in details. In a variety of bacterial species, including Mycobacterium tuberculosis, ADP-ribosylation of thymidine has emerged as the mode of action of a toxin-antitoxin system named DarTG, with the resultant products perceived as DNA damage by the cell. On the other hand, mammalian DNA damage sensors PARP1, PARP2 and PARP3 were shown to ADP-ribosylate phosphorylated ends of double-stranded DNA in vitro. Additionally, TRPT1 and several PARP enzymes, including PARP10, can add ADP-ribose to the 5’-phosphorylated end of single-stranded RNA in vitro, representing a novel RNA capping mechanism. Together, these discoveries have led to the emergence of a new and exciting research area, namely DNA and RNA ADP-ribosylation, that is likely to have far-reaching implications for the fields of DNA repair, replication and epigenetics.
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