通过对蛋白质定位动态的定量分析揭示了Rad53检查点激酶的Mec1独立激活
Brandon Ho1,2, Ethan J Sanford3, Raphael Loll-Krippleber1,2
1Department of Biochemistry, University of Toronto, Toronto, Canada.
eLife
|June 6, 2023
概括
DNA复制检查点确保了压力期间的基因组稳定性. 这项研究揭示了Rad53激酶独立于Mec1调节蛋白质定位,揭示了对细胞存活至关重要的新激活通路.
科学领域:
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
- 遗传学 是一个遗传学.
背景情况:
- 在基因毒性压力下,复制检查点对于DNA复制,修复和基因组完整性至关重要.
- 已知在复制应激过程中蛋白质局部化的变化,但对调节机制的了解很少.
研究的目的:
- 研究在Saccharomyces cerevisiae中甲基甲硫酸盐 (MMS) 诱导的复制应激过程中蛋白质亚细胞局部化的调节.
- 确定基本检查点激酶Mec1和Rad53在控制蛋白质运动中的作用.
主要方法:
- 使用甲基甲硫酸盐 (MMS) 诱导DNA复制压力在Saccharomyces cerevisiae.
- 对众多蛋白质的亚细胞局部的量化变化.
- 对Rad53调节的基因酶依赖性 (Mec1,Tel1) 和介质蛋白 (Rad9,Mrc1) 进行了研究.
- 在各种突变背景下评估Rad53酸化和活性.
- 研究了Rtg3在Rad53激活和复制动态中的作用.
主要成果:
- 在MMS压力期间,Mec1和Rad53调节了159种蛋白质的局部化.
- Rad53控制了52种蛋白质的局部化,独立于Mec1,Tel1,Rad9或Mrc1.1.
- 在暴露于MMS后,Rad53被酸化并活跃在Mec1/Tel1缺乏细胞中.
- 非正规的Rad53激活部分取决于Rtg3,这也影响了DNA复制.
结论:
- 在应对复制应激时,确定了Rad53激酶的Mec1/Tel1独立的新型激活通路.
- 证明Rtg3在这种并行Rad53激活途径中发挥作用.
- 强调了检查点调节的复杂性,并行途径有助于基因组稳定.
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