与PCNA结合的Srs2及其相化在DNA损伤反应期间有助于RPA对抗性
Jiayi Fan1, Nalini Dhingra1, Tammy Yang2
1Molecular Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065.
bioRxiv : the preprint server for biology
|April 8, 2024
概括
DNA损伤检查点被Srs2 DNA酶下调,它从DNA中去除RPA和Mec1检查点酶. 这个过程由Srs2结合PCNA和sumoylation来调节,确保及时的检查点终止和DNA保护.
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 是一个遗传学.
背景情况:
- DNA损伤检查点对于基因组稳定至关重要,在暴露于基因毒素时阻止细胞循环的进展.
- 检查点下调允许在长时间的压力后恢复细胞循环,但其调节尚未完全理解.
- 众所周知,在酵母中,Srs2 DNA 螺旋酶通过去除 RPA 和 Mec1.1 来降低DNA损伤检查点的调节.
研究的目的:
- 调查Srs2的反检查点角色的时间和空间调节.
- 阐明控制Srs2活动在检查点下调监管的监管机制.
- 了解Srs2如何防止多余的RPA被移除,同时允许检查点恢复.
主要方法:
- 对Srs2调节元件 (酸化,化,蛋白相互作用) 的遗传分析.
- 在酵母细胞中的检查点水平评估.
- 检查Srs2对PCNA的结合及其对RPA去除的影响.
主要成果:
- 通过将Srs2与PCNA结合起来,将其招募到特定的ssDNA区域,从而促进了Srs2的RPA反击作用.
- 取决于Srs2-PCNA相互作用和Mec1活性的Srs2化,进一步增强了RPA对抗性.
- 提出了检查点下调的两步模型,涉及Srs2招募和Mec1过度激活时的sumoylation.
结论:
- Srs2活动在空间和时间上受到调节,以确保有效的检查点终止.
- PCNA结合和相化是Srs2在DNA损伤检查点恢复中的作用的关键调节者.
- 这一规则最大限度地减少了RPA在未受保护的ssDNA上的去除,从而保持了DNA的完整性.
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