Both activation and termination of DNA damage response (DDR) are essential to maintain genome stability. It is well-known that the histone variant H2AX is rapidly phosphorylated to activate DDR in eukaryotes. But how H2AX signaling is terminated remains poorly understood, especially in plants. Through forward genetic screening in Arabidopsis, we find that the DNA Damage Response Mutant 5 (ddrm5) mutant is hypersensitive to DNA damage-inducing reagents. Gene mapping and genetic complementation analysis reveal that DDRM5 encodes a plant-unique phosphatase MAIL3, whose phosphatase domain is necessary and sufficient for its function in DDR. Biochemically, MAIL3 physically interacts with and dephosphorylates H2AX, promoting its polyubiquitination at Lys103 and Lys127 by the E3 ubiquitin ligase SCFAFB1, which results in H2AX degradation through the proteasome. Genetically, loss of H2AX or overexpression of AFB1 rescue the DDR defects of the mail3 mutant. Taken together, this study identifies MAIL3 and SCFAFB1 as the first phosphatase and the first E3 ubiquitin ligase for plant H2AX, highlighting the importance of H2AX dephosphorylation and polyubiquitination in DDR termination.
{"title":"Dephosphorylation and polyubiquitination of the histone variant H2AX coordinately terminate DNA damage signaling in Arabidopsis.","authors":"Xuerui Lu, Xiaodan Yu, Zhiping Deng, Zhichao Wang, Lvwen Zhang, Shixi Shi, Lili Wang, Shunping Yan","doi":"10.1016/j.molp.2025.12.029","DOIUrl":"https://doi.org/10.1016/j.molp.2025.12.029","url":null,"abstract":"<p><p>Both activation and termination of DNA damage response (DDR) are essential to maintain genome stability. It is well-known that the histone variant H2AX is rapidly phosphorylated to activate DDR in eukaryotes. But how H2AX signaling is terminated remains poorly understood, especially in plants. Through forward genetic screening in Arabidopsis, we find that the DNA Damage Response Mutant 5 (ddrm5) mutant is hypersensitive to DNA damage-inducing reagents. Gene mapping and genetic complementation analysis reveal that DDRM5 encodes a plant-unique phosphatase MAIL3, whose phosphatase domain is necessary and sufficient for its function in DDR. Biochemically, MAIL3 physically interacts with and dephosphorylates H2AX, promoting its polyubiquitination at Lys103 and Lys127 by the E3 ubiquitin ligase SCF<sup>AFB1</sup>, which results in H2AX degradation through the proteasome. Genetically, loss of H2AX or overexpression of AFB1 rescue the DDR defects of the mail3 mutant. Taken together, this study identifies MAIL3 and SCF<sup>AFB1</sup> as the first phosphatase and the first E3 ubiquitin ligase for plant H2AX, highlighting the importance of H2AX dephosphorylation and polyubiquitination in DDR termination.</p>","PeriodicalId":19012,"journal":{"name":"Molecular Plant","volume":" ","pages":""},"PeriodicalIF":24.1,"publicationDate":"2025-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145863869","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-22DOI: 10.1016/j.molp.2025.12.021
Dongsheng Yu, Chuanli Ju, Zebin Liu, Changxin Feng, Yu Wang, Yujia Sun, Lei Gao, Chunyan Li, Enjie Yu, Xuan He, Haimei Su, Mengchen Hu, Yidong Wang, Jiayi Liu, Jie Meng, Shen Tian, Liangyu Liu, Congcong Hou, Dongdong Kong, Legong Li
The gaseous hormone ethylene plays a key role in regulating plant growth and stress responses. Although Ca2+ has long been implicated in ethylene signaling, the identity of molecules controlling Ca2+ permeability has remained elusive. Here we show that Arabidopsis subfamily I ethylene receptors ETR1 and ERS1, as well as their homologs across the green lineage, are Ca2+ permeable. We found that simultaneous disruption of ETR1 and ERS1 markedly attenuates ethylene-induced elevation in cytosolic Ca2+ concentrations in Arabidopsis seedlings, and that both proteins exhibit Ca2+ permeability in the Xenopus laevis oocyte system and two additional heterologous expression systems. Moreover, we showed that homologs of ETR1 from eight land plant and algal species also exhibit Ca2+ permeability, suggesting an evolutionarily conserved function. We further demonstrate ethylene enhances the Ca2+ permeability of ETR1 and its homologue from the charophyte Klebsormidium flaccidum, and a mutation to disrupt ethylene binding (Cys65Ser) abolishes the ethylene influence. These findings uncover a previously unrecognized yet conserved role of ethylene receptors as Ca2+-permeable channels in the green lineage, with broad implications for Ca2+ signaling in plant development and environmental adaptation.
{"title":"Subfamily I ethylene receptors are functionally conserved in calcium permeability across the green lineage.","authors":"Dongsheng Yu, Chuanli Ju, Zebin Liu, Changxin Feng, Yu Wang, Yujia Sun, Lei Gao, Chunyan Li, Enjie Yu, Xuan He, Haimei Su, Mengchen Hu, Yidong Wang, Jiayi Liu, Jie Meng, Shen Tian, Liangyu Liu, Congcong Hou, Dongdong Kong, Legong Li","doi":"10.1016/j.molp.2025.12.021","DOIUrl":"https://doi.org/10.1016/j.molp.2025.12.021","url":null,"abstract":"<p><p>The gaseous hormone ethylene plays a key role in regulating plant growth and stress responses. Although Ca<sup>2+</sup> has long been implicated in ethylene signaling, the identity of molecules controlling Ca<sup>2+</sup> permeability has remained elusive. Here we show that Arabidopsis subfamily I ethylene receptors ETR1 and ERS1, as well as their homologs across the green lineage, are Ca<sup>2+</sup> permeable. We found that simultaneous disruption of ETR1 and ERS1 markedly attenuates ethylene-induced elevation in cytosolic Ca<sup>2+</sup> concentrations in Arabidopsis seedlings, and that both proteins exhibit Ca<sup>2+</sup> permeability in the Xenopus laevis oocyte system and two additional heterologous expression systems. Moreover, we showed that homologs of ETR1 from eight land plant and algal species also exhibit Ca<sup>2+</sup> permeability, suggesting an evolutionarily conserved function. We further demonstrate ethylene enhances the Ca<sup>2+</sup> permeability of ETR1 and its homologue from the charophyte Klebsormidium flaccidum, and a mutation to disrupt ethylene binding (Cys65Ser) abolishes the ethylene influence. These findings uncover a previously unrecognized yet conserved role of ethylene receptors as Ca<sup>2+</sup>-permeable channels in the green lineage, with broad implications for Ca<sup>2+</sup> signaling in plant development and environmental adaptation.</p>","PeriodicalId":19012,"journal":{"name":"Molecular Plant","volume":" ","pages":""},"PeriodicalIF":24.1,"publicationDate":"2025-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145820314","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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