The FHA domain protein ArnA functions as a global DNA damage response repressor in the hyperthermophilic archaeon Saccharolobus islandicus.
The FHA domain protein ArnA functions as a global DNA damage response repressor in the hyperthermophilic archaeon Saccharolobus islandicus.
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DOI：
10.1128/mbio.00942-23
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发表时间：
2023-08-31
期刊：
影响因子：
6.4
通讯作者：
Huang, Qihong
中科院分区：
文献类型：
--
作者：
Jiang, Zhichao;Lin, Zijia;Gan, Qi;Wu, Pengju;Zhang, Xuemei;Xiao, Yuanxi;She, Qunxin;Ni, Jinfeng;Shen, Yulong;Huang, Qihong
关键词：
叉头相关（FHA）结构域蛋白通过FHA结构域特异性识别磷酸化的苏氨酸，并参与真核生物的多种信号转导过程，尤其是DNA损伤反应（DDR）和细胞周期调控。虽然FHA结构域蛋白存在于原核生物、古细菌和细菌中，但与真核生物相比，其功能远不清楚，并且尚未研究古细菌FHA蛋白是否在DDR中发挥作用。在这里，我们的特点是FHA蛋白的超嗜热Crenarchaeon islandicus（SisArnA）的遗传，生化和转录组学的方法。我们发现Δ SisarnA对DNA损伤剂4-硝基喹啉1-氧化物（NQO）具有更高的抗性。在Δ SisarnA中，编码用于纤毛介导的细胞聚集和DDR后细胞存活的蛋白质的ups基因的转录升高。SisArnA与两个预测的合作伙伴，SisvWA1（SisArnB）和SisvWA2（指定为SisArnE）的相互作用，在体外磷酸化增强。Δ SisarnB对NQO的抗性高于野生型。此外，SisArnA和SisArnB之间的相互作用，这是减少在NQO处理的细胞，是必不可少的DNA结合在体外。这表明SisArnA和SisArnB在体内共同抑制ups基因的表达。有趣的是，Δ SisarnE比野生型对NQO更敏感，并且NQO处理后SisArnA和SisArnE之间的相互作用加强，表明SisArnE在DDR中具有积极作用。最后，转录组学分析表明，SisArnA抑制了一些基因，这意味着古细菌应用FHA/磷酸肽识别模块进行广泛的转录调控。细胞适应不同的环境压力需要一个信号传感器和转换器的细胞生存。蛋白质磷酸化及其与叉头相关结构域蛋白的识别在真核生物中广泛用于信号转导。虽然FHA蛋白存在于古细菌和细菌中，但对其功能的研究，特别是在DNA损伤反应（DDR）中的研究还很有限。因此，FHA蛋白在生命三域中的进化和功能保守性仍然是一个谜。在这里，我们发现，FHA蛋白从超嗜热Crenarcheon islandicus（SisArnA）抑制皮利基因的转录连同其磷酸化的合作伙伴SisArnB。SisArnA去阻遏在DNA损伤的存在下促进DNA交换和修复。事实上，更多的基因，包括十几个参与DDR被发现由SisArnA的调节意味着FHA/磷酸化模块可能作为一个重要的信号转导通路的转录调控古细菌DDR。
Forkhead-associated (FHA) domain proteins specifically recognize phosphorylated threonine via the FHA domain and are involved in signal transduction in various processes especially DNA damage response (DDR) and cell cycle regulation in eukaryotes. Although FHA domain proteins are found in prokaryotes, archaea, and bacteria, their functions are far less clear as compared to the eukaryotic counterparts, and it has not been studied whether archaeal FHA proteins play a role in DDR. Here, we have characterized an FHA protein from the hyperthermophilic Crenarchaeon Saccharolobus islandicus (SisArnA) by genetic, biochemical, and transcriptomic approaches. We find that ΔSisarnA exhibits higher resistance to DNA damage agent 4-nitroquinoline 1-oxide (NQO). The transcription of ups genes, encoding the proteins for pili-mediated cell aggregation and cell survival after DDR, is elevated in ΔSisarnA. The interactions of SisArnA with two predicted partners, SisvWA1 (SisArnB) and SisvWA2 (designated as SisArnE), were enhanced by phosphorylation in vitro. ΔSisarnB displays higher resistance to NQO than the wild type. In addition, the interaction between SisArnA and SisArnB, which is reduced in the NQO-treated cells, is indispensable for DNA binding in vitro. These indicate that SisArnA and SisArnB work together to inhibit the expression of ups genes in vivo. Interestingly, ΔSisarnE is more sensitive to NQO than the wild type, and the interaction between SisArnA and SisArnE is strengthened after NQO treatment, suggesting a positive role of SisArnE in DDR. Finally, transcriptomic analysis reveals that SisArnA represses a number of genes, implying that archaea apply the FHA/phospho-peptide recognition module for extensive transcriptional regulation. Cellular adaption to diverse environmental stresses requires a signal sensor and transducer for cell survival. Protein phosphorylation and its recognition by forkhead-associated (FHA) domain proteins are widely used for signal transduction in eukaryotes. Although FHA proteins exist in archaea and bacteria, investigation of their functions, especially those in DNA damage response (DDR), is limited. Therefore, the evolution and functional conservation of FHA proteins in the three domains of life is still a mystery. Here, we find that an FHA protein from the hyperthermophilic Crenarchaeon Saccharolobus islandicus (SisArnA) represses the transcription of pili genes together with its phosphorylated partner SisArnB. SisArnA derepression facilitates DNA exchange and repair in the presence of DNA damage. The fact that more genes including a dozen of those involved in DDR are found to be regulated by SisArnA implies that the FHA/phosphorylation module may serve as an important signal transduction pathway for transcriptional regulation in archaeal DDR.
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