Roles of MEM1 in safeguarding Arabidopsis genome against DNA damage, inhibiting ATM/SOG1‐mediated DNA damage response, and antagonizing global DNA hypermethylation
Roles of MEM1 in safeguarding Arabidopsis genome against DNA damage, inhibiting ATM/SOG1‐mediated DNA damage response, and antagonizing global DNA hypermethylation
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MEM1 在保护拟南芥基因组免受 DNA 损伤、抑制 ATM/SOG1 介导的 DNA 损伤反应以及对抗整体 DNA 高甲基化方面的作用
DOI：
10.1111/jipb.13200
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发表时间：
2022
影响因子：
11.4
通讯作者：
Honggui La
中科院分区：
文献类型：
--
作者：
Qianqian Wang;Yumei La;Huihui Xia;Shaoxia Zhou;Zhaoyu Zhai;Honggui La
拟南芥甲基化升高突变体1（mem 1）突变体具有升高的整体DNA甲基化水平。在这项研究中，这种突变等位基因表现出增加的敏感性甲磺酸甲酯（MMS）。Inmem 1突变体是一种参与DNA损伤反应（DDR）的基因，特别是DNA修复相关基因，在没有MMS处理的情况下大部分上调，表明其中DDR通路的激活。MMS处理后，mem 1突变体中多个DNA修复相关基因的表达水平通常低于Col-0植物，这解释了mem 1突变体的MMS敏感表型。在非MMS处理条件下，一组DNA甲基化途径基因在mem 1突变体中上调，导致整体DNA甲基化升高，特别是在RNA指导的DNA甲基化（RdDM）靶向区域。此外，MEM 1似乎有助于共济失调-毛细血管扩张突变型（ATM）和/或γ反应支持因子1（SOG 1）完全激活/抑制由MEM 1和ATM和/或SOG 1同时调节的基因亚组的转录，因为这些基因的表达在MEM 1和ATM和/或SOG 1突变体中一致地减少/增加，但MEM 1突变体中的减少/增加不如ATM和/或SOG 1突变体中那么显著。因此，我们的研究揭示了MEM 1在保护基因组中的作用，以及DNA损伤，DDR激活，DNA甲基化/去甲基化和DNA修复之间的相互关系。
Arabidopsis methylation elevated mutant 1(mem1) mutants have elevated levels of global DNA methylation. In this study, such mutant alleles showed increased sensitivity to methyl methanesulfonate (MMS). Inmem1mutants, an assortment of genes engaged in DNA damage response (DDR), especially DNA‐repair‐associated genes, were largely upregulated without MMS treatment, suggestive of activation of the DDR pathway in them. Following MMS treatment, expression levels of multiple DNA‐repair‐associated genes inmem1mutants were generally lower than in Col‐0 plants, which accounted for the MMS‐sensitive phenotype of themem1mutants. A group of DNA methylation pathway genes were upregulated inmem1mutants under non‐MMS‐treated conditions, causing elevated global DNA methylation, especially in RNA‐directed DNA methylation (RdDM)‐targeted regions. Moreover, MEM1 seemed to help ATAXIA‐TELANGIECTASIA MUTATED (ATM) and/or SUPPRESSOR OF GAMMA RESPONSE 1 (SOG1) to fully activate/suppress transcription of a subset of genes regulated simultaneously by MEM1 and ATM and/or SOG1, because expression of such genes decreased/increased consistently inmem1andatmand/orsog1mutants, but the decreases/increases in themem1mutants were not as dramatic as in theatmand/orsog1mutants. Thus, our studies reveals roles of MEM1 in safeguarding genome, and interrelationships among DNA damage, activation of DDR, DNA methylation/demethylation, and DNA repair.