核孔复合物通过调节染色体上的PCNA水平来调节分端体基因沉默
Sanjeev K Choudhry1, Maxwell L Neal1, Song Li1
1Center for Global Infectious Disease Research, Seattle Children's Research Institute , Seattle, WA, USA.
The Journal of cell biology
|June 26, 2023
概括
核孔综合体 (NPC) 通过控制与DNA结合的增殖细胞核抗原 (PCNA) 水平来调节亚端粒基因沉默. 损失Nup170减少PCNA,损害基因沉默,可以通过增加PCNA水平来挽救.
科学领域:
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
- 遗传学 遗传学 是一个
背景情况:
- 核孔复合体 (NPC) 与染色质相互作用,影响基因表达.
- 在Saccharomyces cerevisiae中的内环核素Nup170与染色体组织和亚端粒基因沉默有关.
研究的目的:
- 阐明Nup170调节基因沉默的机制.
- 为了确定促进Nup170基因调节功能的因素.
主要方法:
- 蛋白质与蛋白质相互作用的研究.
- 基因相互作用分析.
- 转录组相关性分析.
- 对增殖细胞核抗原 (PCNA) 水平的分析.
- 在酵母突变体中进行基因沉默测试.
主要成果:
- 确定了Ctf18-RFC复合体,一种替代的PCNA加载器,作为Nup170功能的促进器.
- Ctf18-RFC被招募到缺乏核篮蛋白 (Mlp1和Mlp2) 的NPC中.
- 努普170缺乏导致DNA上的PCNA水平降低,导致亚端粒基因沉默的丧失.
- 通过删除Elg1来提高PCNA水平,可以挽救nup170Δ突变体中的分端体沉默缺陷.
结论:
- 通过Nup170,NPC调节了分端粒基因沉默.
- 这种调节通过控制DNA结合PCNA的水平来调节.
- 在这种NPC介导的基因沉默途径中,Ctf18-RFC复合体起着关键作用.
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