Dna is a New Target of Parp3
Dna is a New Target of Parp3
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DOI：
10.1038/s41598-018-22673-3
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发表时间：
2018-03-08
影响因子：
4.6
通讯作者：
Lavrik, O. I.
中科院分区：
文献类型：
--
作者：
Belousova, E. A.;Ishchenko, A. A.;Lavrik, O. I.
聚（ADP-核糖）聚合酶家族（PARP家族）的大多数成员具有涉及ADP-核糖从β-NAD +-分子转移到蛋白质受体的催化活性。Talhaoui等人最近发现DNA依赖性PARP 1和PARP 2也可以修饰DNA。在这里，我们证明了DNA依赖性PARP 3可以修饰DNA并形成特定的引物结构，以供修复蛋白进一步使用。我们证明了由PARP 3 ADP核糖基化的缺口DNA可以通过DNA连接酶连接到双链DNA。此外，这种ADP-核糖基化的DNA可以作为一个引发的DNA底物的PAR链延长的纯化蛋白PARP 1和PARP 2以及无细胞提取物。我们认为，这种ADP-核糖修饰可以参与细胞通路，这是重要的细胞生存过程中的双链断裂形成。
Most members of the poly(ADP-ribose)polymerase family, PARP family, have a catalytic activity that involves the transfer of ADP-ribose from a beta-NAD+-molecule to protein acceptors. It was recently discovered by Talhaoui et al. that DNA-dependent PARP1 and PARP2 can also modify DNA. Here, we demonstrate that DNA-dependent PARP3 can modify DNA and form a specific primed structure for further use by the repair proteins. We demonstrated that gapped DNA that was ADP-ribosylated by PARP3 could be ligated to double-stranded DNA by DNA ligases. Moreover, this ADP-ribosylated DNA could serve as a primed DNA substrate for PAR chain elongation by the purified proteins PARP1 and PARP2 as well as by cell-free extracts. We suggest that this ADP-ribose modification can be involved in cellular pathways that are important for cell survival in the process of double-strand break formation.