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Topological Features of Histone H2A Monoubiquitination.
Doklady Biochemistry and Biophysics ( IF 0.8 ) Pub Date : 2020-09-07 , DOI: 10.1134/s1607672920040079
A A Kudriaeva 1 , V M Lipkin 1 , A A Belogurov 1, 2
Affiliation  

Abstract

The cellular response to DNA damage protects the essential information stored in the genome. This mechanism is crucial in terms of the cancer prevention and aging progression. The DNA damage response (DDR) consists of a complex network controlling the cell cycle and multiple mechanisms of the DNA repair. The DDR disruption is a cornerstone feature of the tumor cells, which allows them to enhance beneficial mutations that prevent successful disease treatment. The important checkpoints of the DDR are currently poorly understood due to the complexity and diversity of the DNA repair machinery. Histone ubiquitination is intensively involved in the repair of the double-stranded DNA breaks. This post-translational modification is known to be a key factor in the recruitment of the repair factors to the DNA damage sites. Here, the crucial role of the ubiquitin lysine residue K27 in the process of histone H2A monoubiquitination mediated by the ubiquitin ligase RNF168 has been showed. The presented data suggest forced and intensive diffusion of ubiquitin from the cytoplasm to the nucleus, which is characterized by the dynamic equilibrium less than 10 min. The comparison of the turnover rate of the wild-type ubiquitin and its variant with a single functional lysine residue K27 suggests an important role of the ubiquitin deposition as a covalent conjugate with histone H2A in terms of the stability of the entire ubiquitinome.


中文翻译:

组蛋白H2A单泛素化的拓扑特征。

摘要

细胞对DNA损伤的反应可保护基因组中存储的基本信息。就癌症预防和衰老进程而言,该机制至关重要。DNA损伤应答(DDR)由控制细胞周期的复杂网络和DNA修复的多种机制组成。DDR破坏是肿瘤细胞的基石特征,这使它们能够增强有益的突变,从而阻止成功的疾病治疗。由于DNA修复机制的复杂性和多样性,目前对DDR的重要检查点知之甚少。组蛋白泛素化广泛参与双链DNA断裂的修复。已知这种翻译后修饰是将修复因子募集至DNA损伤位点的关键因素。这里,已显示泛素赖氨酸残基K27在由泛素连接酶RNF168介导的组蛋白H2A单泛素化过程中的关键作用。提出的数据表明遍在蛋白从细胞质向核的强迫和密集扩散,其特征在于动态平衡少于10分钟。将野生型遍在蛋白及其变体与单个功能赖氨酸残基K27的周转率进行比较表明,就整个遍在蛋白组的稳定性而言,遍在蛋白沉积作为与组蛋白H2A的共价缀合物具有重要作用。它的动态平衡时间少于10分钟。将野生型遍在蛋白及其变体与单个功能赖氨酸残基K27的周转率进行比较表明,就整个遍在蛋白组的稳定性而言,遍在蛋白沉积作为与组蛋白H2A的共价缀合物具有重要作用。它的动态平衡时间少于10分钟。将野生型遍在蛋白及其变体与单个功能赖氨酸残基K27的周转率进行比较表明,就整个遍在蛋白组的稳定性而言,遍在蛋白沉积作为与组蛋白H2A的共价缀合物具有重要作用。
更新日期:2020-09-07
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