Both activation and termination of the DNA damage response (DDR) are essential for maintaining genome stability. It is well established that the histone variant H2AX is rapidly phosphorylated to initiate the DDR in eukaryotes; however, how H2AX signaling is terminated remains poorly understood, particularly in plants. Through forward genetic screening in Arabidopsis, we identify the DNA damage response mutant 5 (ddrm5), which is hypersensitive to DNA damage-inducing agents. Gene mapping and genetic complementation analyses reveal that DDRM5 encodes the plant-specific phosphatase MAIL3, whose phosphatase domain is both necessary and sufficient for its function in the DDR. Biochemically, MAIL3 physically interacts with and dephosphorylates H2AX, thereby promoting its polyubiquitination at Lys103 and Lys127 by the E3 ubiquitin ligase SCFAFB1 and leading to proteasome-mediated degradation of H2AX. Genetically, loss of H2AX or overexpression of AFB1 suppresses 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, respectively, that regulate H2AX in plants, highlighting the critical role of H2AX dephosphorylation and polyubiquitination in DDR termination.
{"title":"Dephosphorylation and polyubiquitination of the histone variant H2AX act coordinately to 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":"10.1016/j.molp.2025.12.029","url":null,"abstract":"<p><p>Both activation and termination of the DNA damage response (DDR) are essential for maintaining genome stability. It is well established that the histone variant H2AX is rapidly phosphorylated to initiate the DDR in eukaryotes; however, how H2AX signaling is terminated remains poorly understood, particularly in plants. Through forward genetic screening in Arabidopsis, we identify the DNA damage response mutant 5 (ddrm5), which is hypersensitive to DNA damage-inducing agents. Gene mapping and genetic complementation analyses reveal that DDRM5 encodes the plant-specific phosphatase MAIL3, whose phosphatase domain is both necessary and sufficient for its function in the DDR. Biochemically, MAIL3 physically interacts with and dephosphorylates H2AX, thereby promoting its polyubiquitination at Lys103 and Lys127 by the E3 ubiquitin ligase SCF<sup>AFB1</sup> and leading to proteasome-mediated degradation of H2AX. Genetically, loss of H2AX or overexpression of AFB1 suppresses 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, respectively, that regulate H2AX in plants, highlighting the critical role 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. In this study, we revealed 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 ETR1 and ERS1 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 plants and algal species also exhibit Ca2+ permeability, suggesting an evolutionarily conserved function. We further demonstrated that ethylene enhances the Ca2+ permeability of ETR1 and its homolog from the charophyte Klebsormidium flaccidum, and a mutation disrupting ethylene binding (Cys65Ser) abolishes the effect of ethylene. 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":"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. In this study, we revealed 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 ETR1 and ERS1 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 plants and algal species also exhibit Ca<sup>2+</sup> permeability, suggesting an evolutionarily conserved function. We further demonstrated that ethylene enhances the Ca<sup>2+</sup> permeability of ETR1 and its homolog from the charophyte Klebsormidium flaccidum, and a mutation disrupting ethylene binding (Cys65Ser) abolishes the effect of ethylene. 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}
扫码关注我们
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号