USP37 防止 TRAIP 过早拆解受压力的复原体
Olga V Kochenova1,2, Giuseppina D'Alessandro3,4, Domenic Pilger5
1Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Blavatnik Institute, Boston, MA, 02115, USA.
Nature communications
|June 18, 2025
概括
脱无处不在的酶USP37通过防止在复制压力期间过早的复制体分解来保护基因组的稳定性. 丢失USP37会导致对DNA损伤剂的过敏性,通过抑制TRAIP来挽救这种过敏性.
科学领域:
- 分子生物学分子生物学
- 遗传学 是一个遗传学.
- 细胞生物学 细胞生物学
背景情况:
- 细胞复制体,包括CMG酶,在DNA复制过程中面临障碍,威胁到基因组完整性.
- E3 泛基因酶 TRAIP 针对这些障碍,但需要严格的监管以防止复杂体分解.
研究的目的:
- 研究USP37脱无处不在酶在调节TRAIP活动和在复制压力期间保持基因组稳定性方面的作用.
- 阐明USP37响应拓应激并保护复合体的机制.
主要方法:
- 对USP37淘汰赛人类细胞和Xenopus蛋提取物的分析.
- 用拓酶毒素和复制压力诱导剂进行治疗.
- 对CMG无处不在和拆卸的评估.
- AlphaFold-Multimer用于蛋白相互作用的结构分析.
主要成果:
- 缺乏USP37的细胞对复制应激剂过敏.
- 抑制TRAIP可以挽救USP37淘汰细胞的过敏性.
- 在Xenopus蛋提取物中USP37的耗尽导致TRAIP介导的CMG过早无处不在,并在复杂体停滞时分解.
- USP37与CDC45结合,调解其对拓压力的反应.
结论:
- USP37在保护基因组稳定性方面发挥着关键作用,通过在复制压力期间抑制TRAIP依赖的CMG卸载来保护基因组稳定性.
- USP37充当一个关键的调节器,防止不适当的复制组分解,当复制终止被阻碍.
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