Protein post-translational modifications (PTMs) have emerged to be combinatorial, essential mechanisms used by eukaryotic cells to regulate local chromatin structure, diversify and extend their protein functions and dynamically coordinate complex intracellular signalling processes. Most common types of PTMs include enzymatic addition of small chemical groups resulting in phosphorylation, glycosylation, poly(ADP-ribosyl)ation, nitrosylation, methylation, acetylation or covalent attachment of complete proteins such as ubiquitin and SUMO. Protein arginine methyltransferases (PRMTs) and protein lysine methyltransferases (PKMTs) enzymes catalyse the methylation of arginine and lysine residues in target proteins, respectively. Rapid progress in quantitative proteomic analysis and functional assays have not only documented the methylation of histone proteins post-translationally but also identified their occurrence in non-histone proteins which dynamically regulate a plethora of cellular functions including DNA damage response and repair. Emerging advances have now revealed the role of both histone and non-histone methylations in the regulating the DNA damage response (DDR) proteins, thereby modulating the DNA repair pathways both in proliferating and post-mitotic neuronal cells. Defects in many cellular DNA repair processes have been found primarily manifested in neuronal tissues. Moreover, fine tuning of the dynamicity of methylation of non-histone proteins as well as the perturbations in this dynamic methylation processes have recently been implicated in neuronal genomic stability maintenance. Considering the impact of methylation on chromatin associated pathways, in this review we attempt to link the evidences in non-histone protein methylation and DDR with neurodegenerative research.

中文翻译：

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非组蛋白甲基化对 DNA 损伤反应和修复途径的调节：对神经退行性变的影响。


蛋白质翻译后修饰 (PTM) 已成为真核细胞用来调节局部染色质结构、多样化和扩展其蛋白质功能以及动态协调复杂的细胞内信号传导过程的组合基本机制。最常见的 PTM 类型包括小化学基团的酶促添加，导致完整蛋白质（如泛素和 SUMO）的磷酸化、糖基化、聚（ADP-核糖基）化、亚硝基化、甲基化、乙酰化或共价连接。蛋白质精氨酸甲基转移酶 (PRMT) 和蛋白质赖氨酸甲基转移酶 (PKMT) 分别催化靶蛋白中精氨酸和赖氨酸残基的甲基化。定量蛋白质组分析和功能测定的快速进展不仅记录了翻译后组蛋白的甲基化，而且还确定了它们在非组蛋白中的存在，这些非组蛋白动态调节大量细胞功能，包括 DNA 损伤反应和修复。目前的最新进展揭示了组蛋白和非组蛋白甲基化在调节 DNA 损伤反应 (DDR) 蛋白中的作用，从而调节增殖和有丝分裂后神经元细胞中的 DNA 修复途径。已发现许多细胞 DNA 修复过程中的缺陷主要表现在神经元组织中。此外，非组蛋白甲基化动态的微调以及这种动态甲基化过程中的扰动最近与神经元基因组稳定性的维持有关。 考虑到甲基化对染色质相关通路的影响，在这篇综述中，我们尝试将非组蛋白甲基化和 DDR 的证据与神经退行性研究联系起来。