基因聚合酶 η 是通过相互排斥的单一-ubiquitination 和单一-NEDDylation 调节的
Natália Cestari Moreno1, Emilie J Korchak2, Marcela Teatin Latancia1
1Laboratory of Genomic Integrity, National Institute of Child Health and Human Development, National Institutes of Health, 9800 Medical Center Drive, Bethesda, MD 20892-3371, USA.
bioRxiv : the preprint server for biology
|October 17, 2024
概括
DNA聚合酶eta (Pol η) 通过无处化和NEDDylation进行调节. 作为一种新的修饰,NEDDylation破坏了聚焦的形成,与无处不在不同.
科学领域:
- 分子生物学分子生物学
- 生物化学 生物化学
- 修复DNA修复DNA的修复
背景情况:
- DNA聚合酶eta (Pol η) 是一种Y家族转化聚合酶,对于在紫外线损坏的模板中进行DNA合成至关重要.
- 对复制分叉的招募取决于PCNA无化及其自身的PCNA相互作用蛋白 (PIP) 动图和C终端无胺结合指 (UBZ) 域.
- 之前的研究表明,Pol η在C端 lysines 处经历单-ubiquitination,这取决于 UBZ 域的ubiquitin 结合.
研究的目的:
- 调查Pol η是否可以通过类似于ubiquitin的蛋白质进行修饰,特别是NEDD8.
- 为了阐明Pol η NEDDylation的机制和调节.
- 为了比较NEDDylation对Pol η的功能影响与ubiquitination的功能影响.
主要方法:
- 用NEDD8.8检测和表征Pol η修饰的生物化学试验.
- 使用其UBZ域对Pol η-NEDD8相互作用的分析.
- 抑制COP9信号酶以调节NEDDylation水平.
- 对聚焦形成的评估 作为对无处不在和NEDDylation的反应.
主要成果:
- 聚是通过类似于乌比基因的蛋白质NEDD8在与乌比基因化相同的C端氨酸残留物中进行修饰的.
- 通过NEDD8和Pol η UBZ域之间的非共价相互作用来调节NEDDylation.
- NEDDylation受到强烈的负调节,COP9信号酶抑制的快速增加证明了这一点.
- 虽然单基化对于聚焦的形成很重要,但NEDDylation似乎破坏了这一过程.
结论:
- 这项研究揭示了DNA聚合酶eta的新型调节机制,涉及到类似于乌比奎丁的蛋白NEDD8.
- 波纳经历单NEDDylation,由COP9信号体调节,并通过其UBZ域进行介导.
- NEDDylation对抗了Pol η招募和焦点形成中的无处不在的功能,突出了这些修饰的不同作用.
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