Serine ADP-ribosylation in Drosophila provides insights into the evolution of reversible ADP-ribosylation signalling.
Serine ADP-ribosylation in Drosophila provides insights into the evolution of reversible ADP-ribosylation signalling.
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DOI：
10.1038/s41467-023-38793-y
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发表时间：
2023-06-02
影响因子：
16.6
通讯作者：
Ahel, Ivan
中科院分区：
文献类型：
--
作者：
Fontana, Pietro;Buch-Larsen, Sara C.;Suyari, Osamu;Smith, Rebecca;Suskiewicz, Marcin J.;Schutzenhofer, Kira;Ariza, Antonio;Rack, Johannes Gregor Matthias;Nielsen, Michael L.;Ahel, Ivan
在哺乳动物DNA损伤反应中，ADP-核糖基化信号对于标记DNA损伤位点以及募集和调节修复因子至关重要。具体来说，PARP 1：HPF 1复合物识别受损的DNA并催化形成丝氨酸连接的ADP核糖基化标记（单-Ser-ADPr），这些标记通过PARP 1单独延伸到ADP核糖聚合物（聚-Ser-ADPr）中。聚丝氨酸-ADPr被PARG逆转，而末端单丝氨酸-ADPr被ARH 3去除。尽管它的意义和明显的进化保守，很少有人知道ADP-核糖基化信号在非哺乳动物动物。HPF 1的存在，但缺乏ARH 3，在一些昆虫基因组中，包括果蝇物种，提出了关于这些物种中丝氨酸-ADP-核糖基化的存在和逆转的问题。在这里，我们通过定量蛋白质组学表明，Ser-ADPr是黑腹果蝇DNA损伤反应中ADP核糖基化的主要形式，并且依赖于dParp 1：dHpf 1复合物。此外，我们的结构和生化研究揭示了果蝇Parg去除单丝氨酸-ADPr的机制。总的来说，我们的数据显示PARP：HPF 1介导的Ser-ADPr作为动物DDR的定义特征。在这个王国内的惊人的保守性表明，生物体，只携带一套核心的ADP-核糖基代谢酶，如果蝇，是有价值的模式生物研究Ser-ADPr信号的生理作用。在DNA损伤反应中，ADP-核糖基化是一条重要的信号通路。在这里，作者利用多学科的方法来建立其在果蝇中的分子基础，并为果蝇作为模式生物的合适性提供证据。
In the mammalian DNA damage response, ADP-ribosylation signalling is of crucial importance to mark sites of DNA damage as well as recruit and regulate repairs factors. Specifically, the PARP1:HPF1 complex recognises damaged DNA and catalyses the formation of serine-linked ADP-ribosylation marks (mono-Ser-ADPr), which are extended into ADP-ribose polymers (poly-Ser-ADPr) by PARP1 alone. Poly-Ser-ADPr is reversed by PARG, while the terminal mono-Ser-ADPr is removed by ARH3. Despite its significance and apparent evolutionary conservation, little is known about ADP-ribosylation signalling in non-mammalian Animalia. The presence of HPF1, but absence of ARH3, in some insect genomes, including Drosophila species, raises questions regarding the existence and reversal of serine-ADP-ribosylation in these species. Here we show by quantitative proteomics that Ser-ADPr is the major form of ADP-ribosylation in the DNA damage response of Drosophila melanogaster and is dependent on the dParp1:dHpf1 complex. Moreover, our structural and biochemical investigations uncover the mechanism of mono-Ser-ADPr removal by Drosophila Parg. Collectively, our data reveal PARP:HPF1-mediated Ser-ADPr as a defining feature of the DDR in Animalia. The striking conservation within this kingdom suggests that organisms that carry only a core set of ADP-ribosyl metabolising enzymes, such as Drosophila, are valuable model organisms to study the physiological role of Ser-ADPr signalling. In the DNA damage response, ADP-ribosylation is an essential signaling pathway. Here the authors utilize a multidisciplinary approach to establish its molecular basis in fruit flies and provide evidence for Drosophila’s suitability as model organism.
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影响因子：
16
作者：
Gibbs-Seymour I;Fontana P;Rack JGM;Ahel I
通讯作者：
Ahel I
DOI：
10.1107/s0907444904019158
发表时间：
2004-12-01
影响因子：
2.2
作者：
Emsley, P;Cowtan, K
通讯作者：
Cowtan, K
影响因子：
9.8
作者：
Ghosh, Shereen G.;Becker, Kerstin;Gleeson, Joseph G.
通讯作者：
Gleeson, Joseph G.
DOI：
10.1107/s090744490903947x
发表时间：
2010-04
期刊：
Acta crystallographica. Section D, Biological crystallography
影响因子：
--
作者：
Cowtan K
通讯作者：
Cowtan K
影响因子：
4.6
作者：
Bordet G;Lodhi N;Guo D;Kossenkov A;Tulin AV
通讯作者：
Tulin AV